iv. javaxisvilis saxelobis tbilisis saxelmwifo universiteti ......simsuqnis sedegadweliwadsi, sul...
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1
iv. javaxiSvilis saxelobis Tbilisis saxelmwifo universiteti
xelnaweris uflebiT
T a m a r z e r e k i Z e
cximovani qsovilis gadanawilebisa da kardiometaboluri
maxasiaTeblebis korelacia leptinTan
d i s e r t a c i a
doqtoris akademiuri xarisxis mosapoveblad
medicinaSi
2015 w.
avtoris stili daculia
2
sadisertacio naSromi Sesrulebulia
Sps “endokrinologiis erovnuli instituti”-s bazaze
samecniero xelmZRvaneli - medicinis mecnierebaTa doqtori,
prof. elene giorgaZe
Tbilisi 2015 weli
3
sarCevi
pirobiTi aRniSvnebi da Semoklebebi 4
Sesavali 5
Tavi 1 literaturis mimoxilva 16
1.1 leptinis aRmoCena 16
1.2 rezistentoba leptinis mimarT 20
1.3 leptinis genderuli dimorfizmi 24
1.4 leptinisa da naxSirwylovani cvlis
kavSiri
26
1.5 leptini da Saqriani diabeti tipi 2 29
1.6 leptini da kardiometaboluri
darRvevebis ganviTarebis riski
31
1.7
1.8
leptini da Zvlis mineraluri simkvrive
kvebis sxvadasxva stilis gavlena
leptinze
35
38
Tavi 2 gamokvlevis masala da meTodebi 41
Tavi 3 gamokvlevis Sedegebi 51
Tavi 4 gamokvlevis Sedegebis ganxilva 68
daskvnebi
praqtikuli rekomendaciebi
77
78
gamoyenebuli literatura 79
pirobiTi aRniSvnebi da Semoklebebi
4
1. smi –sxeulis masis indeqsi
2. Tth - Tireotropuli hormoni
3. met. sindromi – metaboluri sindromi
4. dsl – dabali simkvrivis lipoproteinebi
5. msl – maRali simkvrivis lipoproteinebi
6. DXA – Dual energy X‐ray absorbtiometry (ormagenergetikuli rentgenuli
absorbciometria)
7. cns – centraluri nervuli sistema
8. hrb – hipoTalamusis rkalisebri birTvi
9. ob/ob – obese/obese
10. db/db – diabetes/diabetes
11. pomk – proopiomelanokortini
12. npγ - neiropeptidi γ
13. AgRP ‐ Agouti‐related protein
14. gmp-1 ‐ glukagonismsgavsi-peptidi 1
15. IVF ‐ in vitro ganayofiereba
16. irs-1 – insulinis receptoris substrati 1
17. izh-1 – insulinismsgavsi zrdis hormoni 1
Sesavali
5
problemis aqtualoba
jandacvis msoflio organizaciis monacemebiT Warbi wona da simsuqne
msoflioSi sikvdilobis riskis mxriv mexuTe adgilzea. Warbi wonisa da
simsuqnis SedegadweliwadSi, sul mcire 2,5 milioni adamiani iRupeba
(1).Warbi wona da simsuqne zrdis iseTi sicocxlisTvis saSiSi daavadebebis
risks, rogoricaa Saqriani diabeti tipi 2(44%-mde), insulti da/an
infarqti(23%-mde) da sxvadasxva saxis simsivnuri daavadebebi(7-dan 41%-
mde)(1).aseve izrdeba sxva garTulebebis riskic, rogoricaa Zval-saxsrovani
dakunTovani daavadebebi [2]. simsuqne epidemiur maCvenebels aRwevs
msoflios TiTqmis yvela qveyanaSi, ganurCevlad ganviTarebis donisa.
jandacvis msoflio organizaciis monacemebiT 2008 wlisTvis Warbi wona
aReniSneboda 1.5 miliard zrdasruls (≥ 20 weli). aRniSnuli 1.5
miliardidan, daaxloebiT 200 milion mamakacs da 300 milion qals
aReniSneba simsuqne, rogorc ukve Camoyalibebuli daavadeba. dReisaTvis,
msoflios mosaxleobis yovel meaTe adamians aReniSneba daavadeba -
simsuqne. msgavsi sagangaSo mdgomareobaaa msoflios bavSvTa populaciaSi,
sadac 2010 wlis monacemebiT Warbwoniani bavSvebis ricxvi 5 wlamde asakSi
43 milionsSeadgens [1]. Isfaqti, rom 1980 wlidan Warbi wonisa da simsuqnis
SemTxvevebi gaormagda, sagangaSo da damafiqrebelia.
Warbi wona da simsuqne aseve dakavSirebulia metaboluri sindromis
ganviTarebasTan. Tavis mxriv, metaboluri sindromi orjer zrdis gul-
sisxlZarRvTa daavadebis ganviTarebis risks, 5-jer - Saqriani diabetisa da
2,5-jer- saerTo sikvdilianobis ganviTarebis SemTxvevebs [3].
zemoTqmulidan gamomdinare, sakmaod mniSvnelovania Warbi wonisa da
simsuqnis prevencia. didi mniSvneloba eniWebasimsuqnis garTulebebis
adreul daignostikasa da mkurnalobas, rasac, Tavis mxriv, minimumamde
dayavs masTan dakavSirebuli daavadebebis ganviTarebis riski da
saxelmwifosa Tu kerZo piris mier gaweuli xarjebi.
6
Warbi wonisa da simsuqnis prevenciisa da mkurnalobisTvis, aucilebelia
misi gamomwvevi mizezebis codna. Warbi wona da simsuqne cximovani qsovilis
anomaliuri an Warbi raodenobiT dagrovebis Sedegia. simsuqne kompleqsuri,
mravalfaqtoruli daavadebaa [4]. Warbi wonisa da simsuqnis ZiriTad
gamomwvev mizezad gvevlineba garemo faqtorebi (araswori kveba da umoZrao
cxovrebis wesi).darRveulia balansi energiis miRebasa da gacemas Soris.
bolo aTwleulebis manZilze mosaxleobis racionSi gaizarda iseTi
sakvebis moxmareba, romelic gamdidrebulia cximebiT, naxSirwylebiTa da
mariliT. sanacvlod, mniSvnelovnad Semcirda vitaminebiT, mineralebiTa da
mikroelementebiT mdidari sakvebis wili. Aseveizrdeba umoZrao cxovrebis
wesis mqone adamianTa ricxvi.Aamas garda, Warbi wonisa da simsuqnis
ganviTarebis erT-erT xelSemwyobfaqtorad transportis, teqnikisa da
urbanizaciis gazrdac gvevlineba.Warbi wonisa da simsuqnis ganviTarebis
aranakleb mniSvnelovan mizezs warmoadgens socio-ekonomikuri da
genetikuri faqtorebi.genetikuri winaswarganwyoba, erT-erTi yvelaze
mniSvnelovani faqtoria simsuqnis ganviTarebis meqanizmSi, rasac cxadyofs
ojaxis wevrebsa da tyupebze Catarebuli kvlevis Sedegebi [5-6]. dadgenilia,
rom simsuqnis ganviTarebis 40-70% dakavSirebulia genetikur
winaswarganwyobasTan.
cnobilia, rom madis regulaciaSicentraluri roli hipoTalamuss
ekuTvnis; hipoTalamusSi SimSilis centri ganlagebulia mis lateralur
birTvebSi, xolo maZRrobis centri ganlagebulia ventromedialur
birTvebSi. energiis homeostazis regulireba tvinis mier xdeba im
signalebis meSveobiT, romelic modis rogorc cximovani qsovilidan, ise
kuW-nawlavis traqtidan [7-9].
sul ufro meti axali kvleva cxadyofs, rom simsuqnis kidev erTi mizezi
SesaZloa iyos cximovan qsovilSi mimdinare anTebiTi procesi da/an
hormonuli cvlileba. cximovani qsovili gvevlineba sxvadasxva
metabolurad aqtiuri nivTierebebis – adipokinebis sinTezis adgilad. es
cilebi mniSvnelovan rols asruleben metaboluri procesebis
regulaciaSi, vinaidan aqvT auto- da parakrinuli moqmedeba. amas garda,
7
isini aregulireben sxvadasxva organoTa sistemis muSaobas, anu avlenen
tipiur endokrinul aqtivobas. erT-erT aseT adipokins warmoadgens
leptini. Sesabamisad cximovani qsovili mniSvnelovani endokrinuli
organoa.cximovan qsovilSi gamomuSavebul Tavisufal cximovan mJavebsa da
adipokinebs mniSvnelovani gavlena aqvT glukozis homeostazze.
adipocitebi nawilobriv monawileoben insulinis mimarT mgrZnobelobis
regulaciaSi, ris gamoc gvevlinebian simsuqnesa da insulinrezistentobas
Soris damakavSirebel rgolad [10, 11]. simsuqniT gamowveuli hormonebisa da
anTebiTi citokinebis sekreciis darRvevam, SesaZloa gavlena iqonios
metaboluri garTulebebis ganviTarebaze [12].
cximovani qsoviliTavisi aRnagobiT, SemadgenlobiT sakmaod saintereso
endokrinuli organoa. mniSvnelovani gansxvavebaa kanqveSa da visceralur
cximovan qsovils Soris. visceralur cximovan qsovilSi gamomuSavebuli
hormonebi gadadian karis venis mimoqcevaSi da aqvT pirdapiri gavlena
RviZlSi mimdinare metabolur procesebze. kanqveSa cximovan qsovilSi
producirebuli nivTierebebi ki xvdebian sistemur cirkulaciaSi. kanqveSa
da visceralur cximovan qsovils Soris gansxvaveba receptorebis
ganlagebaSic SeimCneva. aRniSnulidan gamomdinare, cximovani qsovili
heterogenuli organoa; misi sekretoruli funqcia damokidebulia sakuTar
zedapirze arsebuli receptorebis lokalizaciaze [13-15].
sworedaRniSnulis gamo centralurad ganlagebuli cximovani qsovili,
romelic xSirad gvxvdeba simsuqnis dros, mWidrod korelirebs sxvadasxva
metabolur garTulebebTan.
leptins mniSvnelovani adgili uWiravs sxeulis masis regulaciaSi. misi
raodenoba sxeulis cximovani qsovilis pirdapirproporciulia, cximovani
qsovili ki,Tavis mxriv, gavlenas axdens leptinis doneze. amasTan, sxva
faqtorebi, rogoricaa maRalkaloriulida Warbi odenobiT sakvebis miReba,
Zili, sxeulis temperatura, sqesi, cirkaduli riTmi da sxva hormonebi, maT
Soris insulini, zrdis hormoni, glukokortikoidebi, testosteroni da
farisebri jirkvlis hormonebi, moqmedeben leptinis sekreciasa da
eqspresiaze.
8
SratSi leptinis gazrdili done upiratesad gvxvdeba simsuqnisa da
cximovani qsovilis abdominur midamoSi Calagebis dros da is warmoadgens
damoukidebel risk-faqtors metaboluri darRvevebisganviTarebisa [16-18].
leptinis aRmoCenidan garkveuli periodis Semdeg, man yuradReba miipyro,
rogorc ara marto cximovani masis maregulirebeli erT-erTi komponenti,
aramed rogorc cximovani qsovilis mier Zvlovani qsovilis dacvis
savaraudo mediatori. Zvlovan qsovilze simsuqnis dacviTi gavlenis
mizezad didi odenobiT cximovani qsovili miiCneoda.cnobilia, rom
leptinis produqcia xdeba cximovani ujredebis mier da is pirdapir
asaxavs cximovani qsovilis odenobas organizmSi. didi xnis manZilze iyo
gavrclebuli mosazreba, rom simsuqniT daavadebul pirebs koronaruli
daavadebebis ganviTarebismaRali albaToba aqvT, Tumca dabali aqvT
osteoporozis ganviTarebis riski.dReisaTvis leptinsa da Zvlovan
sistemaze Catarebuli kvlevebis Sedegebi gansxvavebulia; kerZod, leptini
avlenda rogorc dadebiT, ise uaryofiT efeqts an araviTarigavlena ar
hqonda Zvlis mineralur simkvriveze.rigi kvlevebis Tanaxmad leptini wonis
matebasTan erTad xels uwyobs Zvlis simkvrivis gazrdasac. leptinis
absoluturi deficitis dros ob/ob virTagvebisTvis leptinis Seyvana wonis
klebasTan erTad amcirebda Zvlis simkvrivesac. rigi kvlevebis Tanaxmad
Warbi cximovani qsovili SesaZloa ar warmoadgendes damcav meqanizms,
Zvlis simkvrivis daqveiTebis winaaRmdeg [19].
rac ufro maRalia smi an welis garSemoweriloba, miT ufro metia Sratis
leptinis done [20]. Sratis leptinis momatebuli done dakavSirebulia
kardiometabolur risk- faqtorebTan, rogoricaa hipertenzia, insulinis
mimarT rezistentoba da Saqriani diabeti tipi 2 [21-28]; im kvlevebis
Sedegebi, romelSicikvleven leptinis kavSirs metabolur
markerebTangansxvavebulia[29-31]. upiratesad aseTi saxis kvlevebi
Catarebulia socio-ekonomikurad mZlavr qveynebSi. ganviTarebad qveynebSi
maTi ricxvi mcirea. saqarTveloSi ki msgavsi xasiaTis kvleva jer ar
Catarebula. saqarTveloSi leptinsa da Zvlis simkvrivis daqveiTebiT
mimdinare daavadebebs Soris kvleva ar Catarebula.
9
aqedan gamomdinare, Cveni kvlevis mizania davadginoT:
leptinisgavlena metabolur maxasiaTeblebze, kardiometabolur risk-
faqtorebsada Zvlis mineralur simkvriveze20-dan 70 wlis asakis mqone
qarTvel qalebSi.
10
kvlevis amocanebi:
kvlevis mizanis gansaxorcieleblad daisaxa Semdegi amocanebi:
1. Sratis leptinis saSualo ariTmetikuli maCveneblis gansazRvra
sakontrolo jgufSi, romelsac sxeulis normaluri masis mqone
pirebi Seadgenda;
2. Warbi wonis an/da simsuqnis mqone pacientebis gamokvleva, Sratis
leptinis saSualo ariTmetikuli maCveneblisdasadgenad;
3. aRniSnuli pacientebisTvis im parametrebis gamokvleva, romelic
zrdis kardiometaboluri darRvevebis risks.
4. sxeuliskompoziciis gansazRvra, romelic moicavs cximovani,
kunTovani da Zvlovani qsovilis raodenobis Sefasebas.
5. leptinsa da kardiometabolur risk-faqtorebs Soris korelaciis
gamovlena.
6. leptinsa da sxeulis kompozicias Soris korelaciis gamovlena.
7. Leptinsa daZvlis mineralur simkvrives Soris korelaciis dadgena.
8. kvebis sxvadasxva stilis gavlenis Seswavla leptinis donesa da
wonaze (kg), iseve rogorc maTi efeqturobis Sedareba.
11
naSromissamecniero siaxle
kvlevis Sedegad SesaZlebeli gaxda leptinis saSualo
ariTmetikuli donis gansazRvra da misi kavSiris dadgena
metabolur darRvevebTan rogorc normaluri wonis, ise Warbi
wonisa da simsuqnis mqone 20-70 wlis qarTvel qalebSi.
aRniSnuli kvleva pirvelia saqarTveloSi, romelic gamoavlens
ara marto leptinis korelacias kardiometabolur risk-
faqtorebTan, aramed mis kavSirs cximovani qsovilis gadanawilebis
Taviseburebebsa da Zvlis mineralur simkvrivesTan.
aRniSnuli kvleva pirvelia saqarTveloSi, romelic ikvlevs
kvebissxvadasxva stilis gavlenas leptinis doneze.
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naSromis praqtikuli Rirebuleba
aRniSnuli kvlevasaSualebas mogvcems davadginoT hiperleptinemiiskavSiri
metaboluri darRvevebis ganviTarebis riskTan normaluri wonis, Warbi
wonisa da simsuqnis mqone pirebSi.asevegamovavlinoTleptinis korelacia
Zvlis mineralur simkvrivesTan, da ganvsazRvroT warmoadgens Tu ara
igimotexilobis ganviTarebis prediqtors da SevadaroT sxvadasxva kvebiTi
komponentisgan Semdgari dietis gavlenaleptinis doneze.
13
disertaciis dasacavad gasatani ZiriTadi debulebebi
1.gamovlindakorelacia Sratis leptinsa da smi-s Soris. smi-is zrdasTan
erTad izrdeba Sratis leptinis done 20-70 wlis asakis mqone qarTvel
qalebSi.
2. Sratis leptini dadebiTad korelirebs iseT kardiometabolur risk-
faqtorebTan rogoricaa, welis garSemoweriloba, sistoluri da
diastoluri arteriuli wneva, abdominuri simsuqne, trigliceridebis,
dabali simkvrivis lipoproteinebisa da glukozis done uzmod.
3. Sratis leptinis donis zrdasTan erTad mcirdeba Zvlis mineraluri
simkvrive zrdasrul qalebSi.
4. naxSirwylovani sakvebis SezRudva sakveb racionSiufro metad aqveiTebs
leptinis dones, cximebiT Rarib dietasTan SedarebiT
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sadisertacio Temis garSemo gamoqveynebuli publikaciebis sia:
1. Bлияние лептина на минеральную плотность костив пременопаузе и постменопаузе
(Шанава Ш.Г., Зерекидзе Т.В., Амашукели М. Т., Асатиани К. А.,
GeorgianMedicalNews);
2. Serum Leptin Concentration with Body Fat Distribution in Georgian Population”; First
International Diabetes and Obesity Forum, Athens, Greece, 21‐23 of October 2010,
poster presentation;
3. Androgen Deficiency and insulin resistance in obese male patients; First International
Diabetes and Obesity Forum, Athens, Greece, 21‐23 of October 2010);
4. hiperleptinemia da kardiometaboluri maxasiaTeblebi; T. zerekiZe, S.
janjRava, l. uCava, q. asaTiani, e. giorgaZe; eqsperimentuli da
klinikuri medicina #4, 2014, gv. 57-63;
5. androgendeficiti da insulinrezistentoba simsuqniT daavadebul
mamakacebSi, S. janjRava, l. uCava, e. giorgaZe, q. asaTiani, T.
zerekiZe; #4, 2014, gv. 70-77;
6. Hyperletinemia May Protect From Cardio‐vascular Complications: A Small Georgian Study;
T. Zerekidze, Sh. Janjgava, K. Asatiani, E. Giorgadze; Maced J Med Sci; doi.
org/10.3889/MJMS.1857‐5773.2014.0433;
7. Influence of testosterone replacement therapy on metabolic disorders in male patients
with type 2 diabetes mellitus and androgen deficiency.Janjgava S, Zerekidze T, Uchava L,
Giorgadze E, Asatiani K.Eur J Med Res. 2014 Oct 23;19(1):56.
15
sadisertacio naSromis struqtura da moculoba
sadisertacio naSromi gadmocemulia qarTul enaze,94nabeWdgverdze da
Sedgeba Semdegi Tavebisgan: Sesavali, literaturis mimoxilva, gamokvlevis
masala da meTodebi, sakuTari kvlevis Sedegebi, sakuTari kvlevis Sedegebis
ganxilva, daskvnebi, praqtikuli rekomendaciebi; citirebulia
245gamoyenebuli literaturis wyaro. sadisertacio naSromi moicavs10
cxrils, 2 suraTs da 12 grafiks.
16
Tavi 1. literaturis mimoxilva
1.1 leptinis aRmoCena
leptini upiratesad TeTri cximovani ujredebis mier sinTezirebuli
hormonia [32-33]. Tumca,leptinis sinTezi aseve xdeba: rux cximovan qsovilSi,
placentaSi (sincitiotrofoblastebi), sakvercxeebSi, kunTovan qsovilSi,
kuWSi (fundusi da P/D1 ujredebi), sarZeve jirkvlis epiTelur ujredebSi,
Zvlis tvinSi, hipofizsa da RviZlSi [34‐37].
Hhormoni leptini aRmoaCines 1994 wlis dekemberSi.Friedman-is jgufma
moaxdina simsuqnis (ob) genis klonireba, romelic pasuxismgebelia
simsuqnis, diabetisa da insulinrezistentobis mqone ob/ob virTagvebis
fenotipze [38].maleve aRmoaCines am genis cilovani produqti da plazmaSi
misi koncentraciis gansazRvris meTodebic SemuSavda [39]. obgenis am
produqts leptini ewoda, rac warmosdgeba berZnuli sityva “leptos”-idanda
Txels niSnavs; saxelwodeba SeirCa im funqciis aRsaniSnavad, romelsac
maTi azriT es hormoni asrulebda. am aRmoCenis Semdeg daiwyo mravali
kvleva, raTa sxeulis masis regulaciaSi gansazRvruliyo leptinis
funqcia; am kvlevebis mizani adamianis simsuqnis paTofiziologiis axsna
iyo.
mravali kvleva da dagrovili masala adasturebs, rom leptini
mniSvnelovania ara marto sakvebis miRebisa da energiis balansis
regulaciaSi, aramed mas rigi sxva metaboluri da neiroendokrinuli
gavlena aqvs. misi monawileobiT mimdinareobs normaluri seqsualuri
ganviTareba da reproduqcia; is aseve urTierTqmedebs hipoTalamo-hipofiz-
Tirkmelzeda jirkvlis RerZTan, farisebri jirkvlisa da zrdis
hormonebTan, aseve mas gavlena aqvs glukozis metabolizmze; amas garda,
leptinskavSiri aqvs hematopoezTan, imunur da Zvlovan sistemasTan.
isawvdis informacias Tavis tvins cximovani qsovilis raodenobis Sesaxeb.
mas xatovnad cximovani qsovilis “xmasac” uwodeben. aqve unda aRiniSnos,
17
rom misi moqmedeba xorcieldeba uaryofiTi ukukavSiris principiT.
leptinis funqciaa gansazRvrul doneze sxeulis cximovani maragis
SenarCuneba. mocirkulire leptinis done mWidro kavSirSia cximovani
qsovilis maragTan [38], rac gulisxmobs, rom cximovani qsovilis masis
mateba zrdis leptinis gamomuSavebas, Sesabamisad ki iTrgunebasakvebis
miReba da piriqiT. leptinis makodirebeli genis an misi receptoris
mutaciis dros, virTagvebsa da adamianebSi aRiniSneba morbiduli simsuqnis
adreuli Camoyalibeba [40-44]. dRemde leptinis ukmarobiT gamowveuli
monogenuri simsuqnis mxolod ramdenime SemTxvevaadafiqsirebuli, rac
sakmaod kargad eqvemdebareba rekombinantuli leptiniT mkurnalobas [45-46].
virTagvebis wonis regulaciaSi leptinis roli uaryofiTi ukaukavSiris
ciklSi kargad aris Seswavlili, rasac ver vityviT adamianebze. bolomde
yvelaferi naTeli ar aris. aRsaniSnavia, rom simsuqnis mqone pirebis
umetesobas leptinis done momatebuli aqvs, Tumca es momateba cximovani
masis daklebas ar iwvevs [47-49]. amavdroulad, simsuqnis mqone pirebisTvis
egzogenurad leptinis Seyvana ar amcirebs wonas, es ki miuTiTebs imaze,
rom simsuqnis mqone pirebi leptinis gavlenis mimarT rezistentulni arian
[50].
yovelive zemoTqmuli imaze metyvelebs, rom leptinis ZiriTadi funqcia
mxolod wonis matebis SeferxebaSi ar mdgomareobs. savaraudoa, rom
aRniSnuli sistema ufro cximovani qsovilis maragis Seqmnas ganapirobebs,
vidre misxarjvas. swored amitom, rigi mkvlevaris azriT, leptinis
ZiriTadi fiziologiuri moqmedebaar aris “maZRrobis signalis”
gadacemasimsuqnis prevenciisaTvis.aramed “SimSilis signalis” gadacemaa,
raTa energiis deficitis dros organizmis dasacavad SeinarCunos sakmarisi
cximis maragi [51].
leptinisa da misi receptoris ukmarobisdrosSeiniSnebaerTnairi
fenotipi.esgamoxatuleba gacilebiT ufro naklebia leptinis receptoris
ukmarobis SemTxvevaSi[52]. aseve, leptinis receptoris deficiti SedarebiT
ufro gavrcelebulia da morbiduli simsuqnis yvela SemTxvevis
daaxloebiT 3%-sSeadgens.
leptinis funqciebidan pirvelad aRweres misi gavlena wonis regulaciaze;
adamianebSi misi done mniSvnelovnad korelirebs smi-sa da cximovan
masasTan [40-43]. leptinis sekrecia xdeba adipocitebis mier pirdapir
sisxlis mimoqcevis sistemaSi [42-46]; mas tvinSi miaqvs informacia
organizmSi arsebuli cximovani masis Sesaxeb (sur 1). es hipoTeza
dadasturda kvleviT, sadac ob/ob leptinis deficitis mqone virTagvebSi
leptinis Seyvanam miRebuli sakvebis raodenobis Semcireba da energiis
xarjvis gazrdagamoiwvia [46-49]. normalur virTagvebSicki, msgavsi
Sedegiiqna miRebuli, Tumca, gacilebiT sustad gamoxatuli vidre ob/ob
virTagvebis SemTxvevaSi [47-50].
suraTi 1: leptini centralur nervul sistemaze moqmedebs an pirdapir an
garkveuli centrebis aqtivaciis gziT. is amcirebs sakvebis miRebas, zrdis
energiis xarjvas, gavlenas axdens glukozis da cximis metabolizmze da
cvlis neiroendokrinul aqtivobas.
aRmoCenidan Zalian male moxda leptinis receptorebis klonireba da
aRniSnuli receptorebisgamovlena qorionul wnulsa da hipoTalamusSi; es
is regionebia, romelic monawileobs madis regulaciaSi, sakvebis miRebasa
18
19
da sxeulis masis normalizaciaSi [51-55]. Semdgom moxda im gzebis aRmoCenac,
romliTac leptini axorcilebda Tavis moqmedebas cns-ze.dReisTvis
cnobilia, rom leptini Tavis tvinSi urTierTqmedebs TiTqmis yvela
neiropeptidTan, romelic CarTulia energiis regulaciasa da
gansakuTrebiT kvebiT procesSi. hipoTalamusis rkalisebribirTvi (hrb)
leptinis ZiriTadi samizne ubania [56-57]. hrb-Si gvxvdeba neironebis ori
klasi: pirveli klasi warmodgenilia proopiomelanokortiniTa (pomk) da
kokain/amfetamin-dakavSirebuli transkriptiT, rac amcirebs sakvebis
miRebas, maSin roca meore klasi warmodgnilia ori peptidiT: neiropeptidi
γ(npγ)da AgRP (agouti‐related protein), romlebic astimulireben kvebiT qcevas [58-
59]. leptinis receptorebi didi raodenobiT gvxvdeba orive klasis
neironebze, rac mas saSualebas aZlevs reciprokulad areguliros orive
procesi, rogorc sakvebis miRebis Semcireba, ise misi stimulacia.
hipoTalamusis rkalisebr birTvSi leptini ainhibirebs neiropeptid Y-s (npγ)
sekrecias [60] da paraventrikulur birTvze zrdis kortikotropin
rilizing hormonis eqskrecias [61]. leptinis sapasuxo reaqciaSi CarTulia
sxva gzebic: glukagonis-msgavsi-peptidi 1-is (gmp‐1) sistema, pre-
opiomelanokortinis sistema, neironebi, sadac xdeba oreqsinebis an
hipokretinebis eqspresia, kokain- da amfetamin-maregulirebel transkripti
da galanini [62].
leptinis receptori aris erTSriani cila, romelic struqturulad klasi
I citokinebis receptorebis ojaxis msgavsia [63, 64]. arsebobs leptinis
receptoris (ObR) ramdenime gansxvavebuli izoforma [63], TiToeuli
damaxasiTebeli ujredSida domeniT. swored ujredSida domenis sigrZis
mixedviT izoformebi iyofa mokle da grZel izoformad. mokle izoformas
(ObRa, ObRb, ObRc, ObRd, ObRe da ObRf) aqvs SezRuduli sasignalo unari, maSin
roca grZeli izoforma ObRb, savaraudod receptoris ZiriTadi sasignalo
formaa [63, 65, 66]. mokle izoformaObRa da ObRc didi raodenobiT gvxvdeba
tvinis mikrosisxlZarRvebze, rac warmoadgens hemato-encefalur bariers da
ZiriTad rols asruleben cns-sken leptinis transportSi [67]. savaraudod,
mokle izoforma leptinis transports imonawileobs, Tumca misi moqmedeba
20
jerjerobiT kvlav ucnobia [68]. receptoris grZeli izoforma, ObRbdidi
odenobiT gvxvdeba hipoTalamusSi da swored misi meSveobiT leptini
axorcielebs Tavis moqmedebas energiis homeostazze[66, 69]. ObRb-s
membranuli eqspresia nawilobriv regulirdeba OB‐R genTan SeWiduli
ciliT[70].swored funqciuri ObRb-s ukmarisobaa pasuxismgebeli simsuqnesa
da metabolur sindromze, romelic nanaxia db/db virTagvebis modelSi [71].
mas Semdeg rac aRmoaCines, rom virTagvebis leptinis genis mutacia
ganapirobebda ob/ob fenotips, daibadaaseTiSekiTxva: SeeZlo Tu ara
adamianebSi msgavs mutacias gamoewvia simsuqne?molekuluri skriningis
monacemebis Tanaxmad, leptinis makodirebeli geni simsuqnis mqone pirebis
umetes nawilSi normis farglebSia [72-76]. 2000 wlamde leptinis genis
mutaciiT mxolod ori ojaxi iyo gamovlenili - leptinis Tandayolili
deficitiT [77-79].yvela maTgans aReniSneboda morbiduli simsuqnis
adreuli Camoyalibeba, Warbi cximovani masis miuxedavad leptinis Zalian
mcire done, gamoxatuli hiperfagia da hiperinsulinemia. adamianis
rekombinantuli leptiniT mkurnalobis Sedegad miaRwies wonis klebasa da
yvela metaboluri darRvevis gaumjobesebas [80]. am pacientebis heterozigot
ojaxis wevrebs ar aReniSneboda morbiduli simsuqne da maTi leptinis
donec normis farglebSi iyo.
1.2. rezistentoba leptinis mimarT
leptinis mimarT rezistentoba terminia, romelic organizmis mier
leptinis aRqmis darRvevas aRwers; simsuqnis mqone pirebSi is aseve
aRniSnavs leptinis momatebul dones. arsebobs rigi molekuluri
meqanizmebisa, romelic aRwers leptinis mimarT rezistentobis fenomens. is
moicavs molekuluri da funqciuri darRvevebis farTo speqtrs.
Gamoyofenleptinis mimarT rezistentobis ganviTarebis Semdeg meqanizmebs: a)
leptinis transportis darRveva sisxlidan tvinamde da b) leptinis
receptoris funqciisa da sasignalo Tvisebebis darRvevas. simsuqnisTvis
damaxasiaTebeli qronikulad momatebuli leptinis done amcirebs leptinis
21
transports cns-ken da arRvevs leptinis receptoris sasignalo Tvisebebs.
AmisSedegad, leptinis mimarT rezistentoba zrdis sakvebiT-gamowveuli
simsuqnis ganviTarebas, rac, Tavis mxriv, zrdis leptinis dones da kidev
ufro auaresebs leptinis mimarT rezistentobas; yalibdeba wonis matebis
mankieri wre. aqedan gamomdinare, leptinis mimarT rezistentoba gvevlineba
simsuqnis gamomwvev rogorc mizezad, ise mis Sedegad [81, 82].
garkveulmakvlevebma aCvena, rom hematoencefaluri barieri leptinis mimarT
rezistentobis gaCenis sakvanZo ubania [83-85]. molekuluri masiT 16 kda,
leptini Zalin didiaimisaTvis, rom gaiaros transmembranuli barieri
difuziis gziT, amitomac tvinSi najeri satransporto sistemiT
transportirdeba.leptinis tranporti mTel cns-Sixdeba, Tumca
dakavSirebis yvelaze intensiur ubnad hipoTalamusis hrb-i gvevlineba. cns-
Si leptinis transportze ramodenime faqtorimoqmedebs. mag: α-adrenerguli
stimulacia aZlierebs transports [86], maSin roca hipertrigliceridemia
mniSvnelovnad aqveiTebs mas [87]. hipertrigliceridemia aRiniSneba SimSilis
dros. am SemTxvevaSi mowodebuli hipoTezis Tanaxmad, trigliceridebs aqvT
leptinis transportis inhibirebis unari, rac savaraudod sakvebis
deficitis dros organizmis damcavi meqanizmia. hipertrigliceridemia aseve
asocirdeba simsuqnesTan; am dros leptinis transportis darRveva
savaraudod dakavSirebulia leptinis mimarT periferiul rezistentobasTan
[83-85]. periferiuli rezistentoba, centraluris msgavsad, simsuqnis
ganviTarebis rogorc mizezi, ise Sedegia da gulisxmobs, rom savaraudod
erTdroulad gvxvdebaori tipis rezistentoba (periferiuli da
centraluri); rogorc ki es ori tipis rezistentoba Camoyalibdeba, maSinve
iqmneba wonis matebis mankieri wre [83-85].
Teoriulad leptinis mimarT rezistentoba SeiZleba leptinis sasignalo
gzebis sxvadasxva doneebze ganviTardes [89].es doneebia: receptoris done,
SemakavSirebel cilasTan dakavSirebis darRveva, hematoencefaluri
barieris gavliTtransportis darRveva da post-receptoruli defeqtebi.
22
leptinis mimarT rezistentoba SesaZloa iyos receptoris defeqtis
Sedegi; es defeqti iwvevs leptinis SekavSirebis darRvevas mis
receptorTan. adamianebSi aseTi defeqti sakmaod iSviaTia [89-91]. am mutaciis
mxolod erTi SemTxvevaa aRwerili [88]. ufunqcio receptori sicocxlis
pirvelive TveSi morbiduli simsuqnis Camoyalibebas, hiperfagias,
pubertuli ganviTarebis Seferxebas da zrdis hormonisa da Tireotropuli
hormonis sekreciis darRvevasiwvevs. am mutaciis dros leptinis done
mkveTrad maRalia ojaxis sxva wevrebSi: ojaxis homozigot wevrebSi 500-dan
700 ng/ml-mde, xolo heterozigotebSi 145-dan 362 ng/ml-mde [88].
leptinis receptorTan dakavSirebuli mutaciebi aseve moicavs [89, 90, 92-
96], receptoris SemakavSirebeli an sasignalo Tvisebebis cvlilebebs.
Tumca, am kuTxiT kvlevebi ar moipoveba.
leptinis mimarT rezistentobis aseve SesaZlo meqanizmia, disbalansi
sisxlis SratSi mocirkulire leptinsa da mis SemakavSirebel cilas
Soris. Tu leptinis SemakavSirebeli cila sisxlSi Zalian didi
raodenobiTaa, maSin es aqveiTebs hormonis biologiur moqmedebas.naCvenebia,
rom adamianebSi SekavSirebuli leptinis Sefardeba Tavisufal leptinTan
gamxdar da simsuqnis mqone pirebSigansxvavebulia; Tavisufali leptinis
done dadebiTad korelirebs smi-Tan [97].
leptinis mimarT rezistentoba, aseve SesaZloa gamoiwvios leptinis
darRveulma transportma hematoencefaluri barieris gavliT. cnobilia,
rom am transportSi monawileobs leptinis receptoris mokle izoforma
[98-100], romelic gansakuTrebiT maRali sixSiriT qorionul wnulSi
gvxvdeba [99, 101]. virTagvebSi am saxis rezistentobis dros, leptinze
sapasuxo reaqcia ar warmoiqmneba, maSin roca organizmi egzogenur
leptinze reagirebs (102). adamianebSi naCvenebia, rom leptinis Sefardeba
Tavzurgtvinis siTxesa da Sratis leptins Soris qveiTdeba simsuqnis mqone
pirebSi [99, 100]. amitom leptinis Tavzurgtvinis siTxeSi Sesvlis sxvaoba
mniSvnelovania simsuqnis garkveuli formebis paTogenezis asaxsnelad; Tu
Sratis leptins ar ZaluZs miaRwios misi moqmedebis ubans, is ver gazrdis
leptinis koncentracias centralurad; Sedegad ki dairRveva samizne
ubanSisignalis gadacema.
leptinis mimarT rezistentoba SesaZloa gamoiwvios aseve post-
receptorulma defeqtma;
suraTi #: 2 leptinis mimarT rezistentobis sqematuri gamosaxuleba da
masSi sakvebi nivTierebebis mniSvneloba.
Warbi wonisa da simsuqnis mqone pirebs Sratis leptinis maRali done
aReniSneba.Tavisuflad mocirkulire leptinis didi raodenoba ar iwvevs
kaloriebis miRebis Semcirebasa da energiis xarjvis gazrdas, anu saqme
gvaqvs leptinis rezistentobasTan.wonis kleba asocirdeba leptinis donis
23
24
daqveiTebasTan, leptinis receptoris raodenobis momatebasTan da
mocirkulire Tavisufali leptinis koncentraciis SemcirebasTan.
1.3. leptinis genderuli dimorfizmi
adamianebSi leptinis aRmoCenisTanavecnobili gaxda, rom leptinis doneebs
Soris arsebobs genderuli dimorfizmi. leptinis done qalebSi 2-3-jer
ufro maRalia, vidremsgavsi smi-is mqone mamakacebSi [2, 5]. am gansxvavebas,
SesaZloa safuZvlad udevs gansxvavebuli sxeulis agebuleba; qalebs,
rogorc wesi,cximovani qsovilis ufro maRali procenti da kanqveSa
cximovani qsovili/visceraluri cximis ufro maRali Tanafardoba
aReniSneba. rogorc cnobilia, Sratis leptini mWidrodaa dakavSirebuli
cximovan masasTan da kanqveSa cximTan [103-108]. SesaZloa qalebisTvis
damaxasiaTebeli Warbi cximovani masa da gansakuTrebiT kanqveSa cximi,
ganapirobebs leptinis SedarebiT maRal dones.sainteresoa is faqti, rom
smi-is koreqciisas [109, 110, 111], cximovani masis [112-114] da kanqveSa cximovani
qsovilis [112] daqveiTebis Semdegac, leptinis done mainc gansxvavebulia da
qalebSikvlav maRali rCeba. leptinis donis genderuli sxvaoba
dabadebisTanaveSeiniSneba. [115-118]; gansxvaveba gansakuTrebiT TvalsaCinoa
pubertatis asakSi [118-123].leptinis donis aseTi sxvaoba gogonebsa da
biWebSi nawilobriv aixsneba pubertatis dros gansxvavebuli sxeulis
agebulebiT: gogonebSi ufro metia cximovani qsovili, xolo vaJebSi
sWarbobs kunTovani masa, gansakuTrebiT gviani pubertatis dros.
adamianebSiSeiniSneba leptinis sekreciis progresuli zrda, romelic
kulminacias sqesobrivi momwifebis periodSiaRwevs. gogonebSi, leptinis
done progresulad izrdeba 5-dan 15 wlamde, maSin roca biWebSi, leptinis
donis zrda 5-dan 10 wlamdexdeba, xolo 13 wlis asakisTvis
daqveiTebasiwyebs. amas adasturebs kvleva, romelSic xdebodaleptinis
donis kvleva vaJebSi.kvlevis Tanaxmad leptinis done yvelaze maRal
maCvenebels pubertatis dawyebis momentSiaRwevs, xolo adreuli pubertatis
Semdeg prepubertul dones ubrundeba [124]. ganviTarebis es cvlileba,
25
ganapirobebda biWebSi Sratis testosteronis, xolo gogonebSi
estradiolis donis matebas. SesaZloa, rom leptini aris is metaboluri
barometri, romelic cns-s atyobinebs, rom organizmi mzadaa pubertuli
ganviTarebis dawyebisTvis.
rigi kvlevebis Tanaxmad, leptinis genderul sxvaobaSi cximovani qsovilis
garda sxva faqtorebsac eniWeba mniSvneloba, mag: rogoricaa sasqeso
steroidebi. es damtkicebulia in vitro eqsperimentebiTa da adamianebze
Catarebuli sxva kvlevebis monacemebiT. leptinis genderuli sxvaoba
aixsneba sasqeso hormonebis gansxvavebuli moqmedebiT, gansakuTrebiT,
testosteronis mainhibirebeli efeqtiT, rac emateba sxeulis agebulebis
gansxvavebebs, kerZod,qalebSi meti kanqveSa cximia, romelic met leptins
gamoimuSavebs [125].
naCvenebia, rom in vitro, estrogenebi astimulireben adipocitebidanleptinis
sekrecias [126, 127]; es efeqti, mxolod qalebis cximovan ujredebSia nanaxi
[128]. amasTan aRsaniSnavia, rom leptinis done qveiTdeba ovareqtomirebul
virTagvebSi da sawyis maCvenebels estradioliT CanacvlebiTi mkurnalobis
Semdeg ubrundeba [127, 130]. adamianebSi, egzogenuri
folikulmastimulirebeli hormonis Seyvana IVF‐s (in vitro ganayofierebis)
dros estrogenTan erTad zrdis leptinis dones [131, 132].
estrogenebisgan gansxvavebiT, androgenebs leptinze mainhibirebeli
moqmedebaaqvs. testosteroni adamianis cximovani ujredebidan Trgunavs
leptinis eqspresias da sekrecias [129]. virTagvebSi testosteronis Seyvana
amcirebs leptinis eqspresias [133]. aTletebis mier anaboluri androgenuli
steroidebis moxmareba mniSvnelovnad amcirebs leptinis dones [134], maSin
roca, amave aTletebSi an biWebSi naadrevi pubertatiT testosteronis
produqciis supresia, gonadotropin-rilizing hormonis agonistis SeyvaniT,
piriqiT, zrdis leptinis dones [134, 135]. hipogonadur mamakacebs aReniSneba
leptinis momatebuli done [136], romelic testosteronis SeyvaniT mcirdeba
[137].
26
1.4. leptinisa da naxirwylovani cvlis kavSiri
leptinsa da insulins Soris arsebuli kavSiri SemTxveviTi aRmoCenis
Sedegia.sxeulis cximovani qsovilis masis da miuxedavad uzmod Sratis
leptinsa da insulins Soris korelacia gamovlinda [138, 139,140-142]. am
korelaciis Semdeg daibada SekiTxva -arsebobs Tu ara mizez-Sedegobrivi
kavSiri, da Tu arsebobs, romeli mimarTulebiT? Ddasazustebeli iyo
regulirdeboda Tu ara leptinis sekrecia insuliniT, Tu leptini axdenda
zegavlenas insulinis sekreciasa da efeqtebze.
mraval wyaroze dayrdnobiT, SegviZlia vTqvaT, rom insulins SeuZlia
leptinis eqspresiis regulireba. izolirebul adipocitebze Catarebuli
kvlevebis Tanaxmad, in vitro, insulini astimulirebs leptinis m-rnm-is
eqspresiasa da sekrecias, rogorc virTagvebis, ise adamianis adipocitebSi
[143-147]. amas garda, virTagvebze Catarebulma eqsperimentebma aCvena, rom
insulini iwvevs cximovan qsovilSi ob m-rnm-is gazrdas [143, 148-149] da
plazmis leptinis donis matebas [150; 151]. im virTagvebSi, romelTac
aReniSneboda insulinis deficiti, streptozotocinis zegavlenis Sedegad
leptinis donec mniSvnelovnad daqveiTebuli hqonda: rodesac am
streptozotociniT namkurnalev cxovelebs ukeTebdnen insulinis ineqciebs,
leptinis sekrecia kvlav izrdeboda [148, 151, 152]. analogiurad, insulinis
deficitis mqone diabetian virTagvebSic plazmis leptinis Semcirebuli
done izrdeba insuliniT mkurnalobis sapasuxod [152].
adamianebze Catarebul eqsperimentebSi, hiperinsulinemia iwvevs leptinis
koncentraciis matebas, magram mxolod garkveuli periodis Semdeg [143, 151-
153] da ara momentalurad (varaudia postprandialur hiperleptinemiaze) [138,
153, 154, 155]. RogorcSaqriani diabetitipi 1, aseve tipi 2 dros,
insulinoTerapia zrdis Sratis leptinis dones [140, 156].aseve
dafiqsirebulia insulinomis erTi SemTxveva leptinis sagrZnoblad maRali
doniT; insulinomis qirurgiuli mkurnalobis Sedegad Semcirda rogorc
insulinis, ise leptinis done [157]; am SemTxvevamac kidev erTxel gausva
xazi, rom qronikuli hiperinsulinemia zrdis leptinis eqspresias.
27
mosazreba, imis Taobaze, rom leptini insulinis sekreciisa da aqtivobis
modulatoria, rac insulinisa da glukozis donis daqveiTebas iwvevs, sul
ufro popularuli xdeba da mtkicdeba mravlobiTi kvlevebiTa da
eqsperimentebiT. hiperglikemiis, hiperinsulinemiisa da
insulinrezistentobis mqone ob/ob virTagvebis leptiniT mkurnalobam
SesaZloa moawesrigos yvela aRniSnuli metaboluri darRveva; Tanac imaze
gacilebiT ufro adre, vidre wonis kleba daiwyeba [46, 60, 158]. amas
adasturebs eqsperimenti, sadac nakveb da mSier virTagvebs egzogenurad
Seuyvanes leptini; pirvel jgufSi (nakvebi virTagvebi) leptinis Seyvanam
plazmis insulinis donis daqveiTeba da masTan asocirebuli hiperglikemia
gamoiwvia [159, 160]; meore jgufSi (mSieri virTagvebi) ki leptinis daniSvnam,
rogorc glukozis, ise insulinis donis daqveiTeba gamoiwvia [161, 162].
savaraudod am SemTxvevaSi leptini gavlenas axdens insulinis funqciasa
da sekreciaze.cxovelebSi, leptinis unari daTrgunos insulini SesaZloa
iyos simpaTikur inervaciaze misi gamaaqtivebeli moqmedebis Sedegi [163].
aRsaniSnaviais faqti, rom leptinis funqciuri receptorebi nanaxia
pankreasis β ujredebze [164]. SesaZloa swored es receptorebi
ganapirobebdnen insulinis sekreciis daqveiTebas leptinis administrirebis
sapasuxod.bazaluri da glukoziT stimulirebuli insulinis sekreciis
inhibireba pankreasis kunZulebze nanaxia leptinis an maRali
koncentraciis, an prolongirebuli moqmedebis Sedegad [159, 165-172]. Tumca,
sxva kvlevebma sapirispiro Sedegebi gamoavlina; rogorc Cans insulinis
gamoyofaze leptinis moqmedeba sakmaod specifiuria, rasac adasturebs is
faqti, rom leptinis deficitis mqone db/db da ft/ft virTagvebisqsovilebSi,
aranairi pasuxi ar vlindeboda [159].
savaraudod, leptini moqmedebs insulinis sekreciis fosfolipaza
C/proteinkinaza C gzebis regulaciis doneze. am gzaze aRwerilia leptinis
sxvadasxva safexurzemoqmedeba: a) ujredSida Ca++ koncentraciis daqveiTeba
da atf-mgrZnobiare K+ arxebis gaaqtiveba [166, 169, 173]; b) fosfolipaza C-Ti
ganpirobebuli insulinis sekreciis inhibireba, romelic Zlierdeba ob/ob
virTagvebSi [167, 174]; da g) Ca++ damokidebuli mediatori fosfolipaza C-s
28
sasignalo gzis meore fazaSi, proteinkinaza C-s daqveiTeba [167, 170].
leptinis supresiuli moqmedeba insulinze SesaZloa nawilobriv
gamowveuli iyos fosfodiesTeraza 3B-s aqtivaciiT gziT [171, 175], rac
iwvevs c-amf-is supresias da gmp-1-iT stimulirebuli insulinis sekreciis
inhibirebas. bolo periodSi, nanaxia pankreasis β uredebze insulinis genis
transkrifciaze leptinis pirdapiri zegavlena, rac gamoixateba
preproinsulinis m-rnm-is 50%-iT daqveiTebiT [168, 176]. savaraudod, leptini
ujredis SigniT sxvadasxva doneebze moqmedebs, dawyebuli transkrifciidan
- membranis ganvladobamde, raTa gamoiwvios insulinis rogorc sinTezis,
ise sekreciis inhibireba.
pankreasisβ ujredebis garda, leptinis receptorebi RviZlSi, ConCxis
kunTebsa da cximovan ujredebze (adipocitebSi) vlindeba; es faqti ki
imazemetyvelebs, rom leptinma SesaZloa zegavlena moaxdinos insulinis
samizne am sam klasikur qsovilze (insulindamokidebuli qsovili) da aseve
imoqmedos am qsovilebSi insulinis sapasuxo reaqciaze.
In vivo kvlevebidan Cans leptinis gavlena glukozis utilizaciaze.leptinis
centraluri an i/v infuzia virTagvebSi zrdis RviZlismier da periferiul
mgrZnobelobas insulinze, Sedegad ki izrdeba glukozis utilizacia [161,
177-180]. ob/ob virTagvebis leptiniT mkurnalobis sapasuxod,
viTardebanormoglikemia [9]. imisTvis, rom gaerkviaT TuriTi iyo
gamowveuli misi es efeqti - wonis klebisa Tu pirdapir leptinis
hopoglikemiuri efeqtiT (mag: periferiaze insulinis mimarT mgrZnobelobis
gazrda), Catarda eqsperimenti virTagvebze.ob/ob virTagvebi or jgufad
daiyo; erT jgufs leptiniT mkurnalobdnen, meores ki - kvebis SezRudviT;
wonis klebis garda orive jgufSiinsulinisa da glukozis donis
daqveiTeba aRiniSna. Tumca, leptiniT namkurnalev jgufSi 60%-iT ufro
meti efeqti miiRes [181].sxva kvlevaSiki Seadares virTagvebSi visceraluri
simsuqnis Semcirebis gavlena insulinis moqmedebaze; virTagvebi
gansxvavebuli mkurnalobis mixedviT sam jgufaddaiyo: leptini, β3-
adrenoreceptoris agonisti an kvebis SezRudva. samive jgufSi insulinis
29
RviZlismieri aqtivoba erTnairad gaizarda, Tumca insulinis periferiuli
aqtivobis mniSvnelovani gazrda mxolod leptinis mkurnalobis sapasuxod
SeiniSna [180]. am eqsperimentebidan SegviZlia davaskvnaT, rom leptini
hipoglikemiur moqmedebas avlens, nawilobriv damoukideblad misi wonisa
da cximovani masis daqveiTebis efeqtisgan. amasTan, leptinis moqmedeba
glukozis metabolimze, nawilobriv insulinis efeqtze ar aris
damokidebuli, rac STZ-(streptazotocini)-inducirebul diabetian
virTagvebzeCatarebulma kvlevam aCvena; am kvlevaSi leptiniT mkurnalobam
glukoza normaSi moiyvana da gaaumjobesa insulinis mimarT mgrZnobeloba
insulinis gamoyenebis gareSec [179].
leptinis receptorebi adamianis hepatocitebzecgvxvdeba; SesaZloa leptini
am ujredebSic insulin-damokidebuli aqtivobebis modulatorad gvevlineba
[182]. leptini insulinis sasignalo moqmedebis sawinaaRmdego moqmedebas
avlens, irs-1-isinsulin-damokidebuli Tirozin-fosforilirebis
daqveiTebis gziT [182]; is zrdis fosfoenolpurivat-karboqsikinazas [183,
184] da amcirebs glukokinazis eqspresias [183]; Sedegad izrdeba
glukoneogenezi da qveiTdeba glukogenolizi [183, 184].
periferiul qsovilze leptinis mier insulinis biologiur efeqtze
zegavlenis moqmedebis Sesaswavlad mravali kvlevaCatarda. rigi kvlevebis
Tanaxmad, leptins SeuZlia insulinis aqtivobis gazrda (glukozis
STanTqma da/an lipidebis sinTezi) adipocitebsa [160, 177, 185-187] da
kunTovan ujredebSi [177, 188-191] Tumca, sxva kvlevebma leptinis es efeqti
ver daadastura.
1.5. leptini da Saqriani diabeti tipi 2
ramdenime wlis win pirvelad daisva SekiTxva, Tu ramdenad mniSvnelovania
leptini Saqriani diabetitipi 2 –s ganviTarebaSi [192, 193]. sxvadasxva
kvlevebis Tanaxmad, hiperleptinemias SeuZlia daarRvios insulinis
30
produqcia da periferiaze gamoiwvios an gaaZlieros insulinis mimarT
rezistentoba. Camoyalibda simsuqnis mqone pirebSi insulinrezistentobis/
Saqriani diabetitipi 2 –s ganviTarebis hipoTeza: simsuqnis dros leptinis
maRali done iwvevs hiperglikemias, romlis mizezicaa pankreasis β
ujredebSi glukoziT gamowveuli insulinis sekreciis supresia.
periferiuli insulinrezistentoba, romelic SesaZloa aseve
hiperleptinemiiT iyos gamowveuli, kidev ufro aRrmavebs glukozisadmi
tolerantobis darRvevas, leptiniT-gamowveuli insulinis sekreciis
supresia β ujredebze wydeba da viTardeba hiperinsulinemia. sxva SesaZlo
hipoTezaa: hiperleptinemia iwvevs receptoris mgrZnobelobis moSlas,
irRvevaβ ujredebze leptinis receptoris signali da Sedegad yalibdeba
qronikuli hiperinsulinemia da ganwyoba Saqriani diabetis ganviTarebisadmi
[172].
sxva mxriv, leptins SesaZloa hqondes Saqriani diabetis ganviTarebis
sawinaaRmdegod mimarTuli damcavi moqmedeba, vinaidan is zrdis
periferiaze insulinis mgrZnobelobas da amcirebs sxvadasxva
qsovilebSitrigliceridebis dagrovebas [194, 195].
dReisaTvis arc erTi kvleva ar amtkicebs, rom Saqriani diabeti tipi 2-is
an glukozis mimarT tolerantobis darRvevaSi raime kavSiri aqvs leptinis
an misi receptoris genis mutacias. adamianis ob genis an misi
gamaaqtivebeli faqtoris skriningisasSaqriani diabetitipi 2-
iTdaavadebulebSi aranairi mutacia ar gamovlinda [74, 76]. msgavsi smi-iTa
da cximovani masis mqone Saqriani diabetiT daavadebul da janmrTel
individebSi, leptinis dones Soris gansxvaveba praqtikulad ar SeiniSneba
[109, 197-199]. aseve msgavsia leptinis korelacia Saqriani diabetiT
daavadebul da janmrTel individebSi sxeulis agebulebasTan, insulinTan
da genderul dimorfizmTan[196, 156, 199].
Catarebuli kvlevebidan savaraudoa, rom leptini ainhibirebs insulinis
sekrecias pankreasis β ujredebis doneze; amavdroulad is zrdis
insulinis aqtivobas da glukozis utilizacias. adipocitebis mier
31
leptinis sekrecia mWidrodaa damokidebuli insulinze. adamianebSi,
leptinis da insulinis done erTmaneTTanaadakavSirebuli, Tumca, kvlav
sadavoa is faqti, SeuZlia Tu ara insulins leptinis regulacia. nanaxia
leptinis donis cvlileba insulinis sapasuxod, Tumca es efeqti garkveuli
periodis SemdegSeiniSneba. savaraudod, insulinis es mastimulirebeli
moqmedeba leptinis sekreciaze nawilobriv insulinis adipocitebze
tropuli moqmedebis Sedegia.
1.6. leptini da kardiometaboluri darRvevebis riski
bolo wlebSi leptinis sekrecia da misi koncentraciis Seswavla sakmaod
aqtualuria simsuqnisa da Saqriani diabetitipi 2-iTdaavadebul pacientebSi;
Sedegad, momravlda leptinze Catarebuli kvlevebis ricxvic. arsebobs
monacemebi, rom Sratis leptinis done izrdeba simsuqnis mqone pirebsa da
Saqriani diabetiT daavadebulebSi. eqsperimentuli kvlevis SedegebiT
hiperleptinemiam SesaZloa pirdapir an meoradad imoqmedos gul-
sisxlZarRvTa daavadebis ganviTarebaze [200].garkveuli kvlevebis Tanaxmad
mniSvnelovani kavSiri gamovlinda Sratis leptinis donesa da
insulinrezistentoba/anTebis markerebs Soris, rac imazemetyvelebs, rom
leptini SesaZloa gvevlinebodes gul-sisxlZarRvTa daavadebebis risk-
faqtorad. Tumca, arsebobs kvlevebi, sadac leptinis korelacia ar
gamovlinda leptinis donesa da gulis koronarul daavadebas Soris [201,
202]. urTierTsapirispiro Sedegebis gamo Kajikawa da Tanaavt. Caatares
kvleva, romlic ufro klinikuri kuTxiT mimdinareobda. am kvlevis erT-
erTi mizani iyo leptinis kavSiris gamovlena metaboluri sindromis da
gulis koronaruli daavadebis riskTan, sxvadasxva koronaruli risk-
faqtorebis mqonepacientebSi. kvlevaSi monawileoba miiRo 104-ma pacientma,
visac ukve dasmuli hqonda metaboluri sindromis diagnozi, an
aReniSneboda sul mcire erTi koronaruli risk-faqtori. kvlevis Sedegebis
Tanaxmad, yvela pacientSi, leptinma dadebiTi korelacia aCvena welis
garSemowerilobasTan, smi-Tan da insulinrezistentobis ideqsTan. leptinis
32
yvelaze maRali cifri aramwevel qalebSidafiqsirda. metaboluri
sindromis jgufSi leptinis done ufro maRaliiyo; aseve ufro maRali iyo
uzmod insulinis done da Homa‐IR-indeqsi (P<0,01). multivariaciulma
analizma gamoavlina, rom leptini dadebiTad korelirebs metabolur
sindromTan. rac Seexeba gulis koronarul daavadebas, leptinis donis
mxriv aranairi mniSvnelovani sxvaoba ar gamovlinda pacientebSi gulis
koronaruli daavadebiT da mis gareSe (leptini 1,79 ±0,12 vs 1,91 ± 0,10).
Kajikawa da Tanaavt. mier Catarebuli kvlevis Tanaxmad leptini dadebiTad
korelirebs metabolur sindromTan. miuxedavad imisa, rombolo wlebSi
Catarebuli ramdenime kvlevis Tanaxmad leptini xels uwyobs
aTerosklerozis da kardiovaskuluri daavadebebis ganviTarebas simsuqnis
mqone pacientebSi, am kvlevam msgavsi Sedegi ver gamoavlina da Sesabamisad
ver hpova dasabuTeba im mosazrebam, romlis Tanaxmadac leptini SesaZloa
pirdapir asocirdebodes gulis koronarul daavadebasTan [203], Tumca,
metabolur sindromTan korelacia aCvenebs, rom meoradad leptini,
SesaZloa zrdis kardiometaboluri darRvevebis ganviTarebis risks.
adipokinebis rolis gamosakvlevad, Warbi wonisa da simsuqnis mqone
pacientebSi, .metabolur sindromiT da mis gareSe dainteresdnen Maria
Gnacińska da Tanaavt. maT mier Catarebul kvlevaSi monawileobda 55
pacienti (38 – metaboluri sindromiT da 17 – metaboluri sindromis
gareSe). kvlevis Sedegebidan gamomdinare orive jgufis pacientebSi Sratis
leptinis done msgavsi iyo.
Marie-He´le`ne Gannage´-Yared da Tanaavt. kvlevis Tanaxmad leptini
dakavSirebulia insulinis mgrZnobelobasTan, damoukideblad asakisa da
smi-sa. amave kvlevis Tanaxmad gamovlinda korelacia leptinsa da smi-s
Soris, Tumca leptinis korelacia lipidur speqtrTan sakmaod sustad iyo
gamoxatuli. smi-is gaTvaliswinebis Semdeg, leptinsa da lipidebs Soris
korelacia mTlianad gaqra, insulinis mimarT mgrZnobelobis raodenobrivi
indeqsis mniSvneloba ki ar Secvlila. msgavsi Sedegebi miiRes Baratta-s da
Tanaavt. mier CatarebulkvlevaSi [204] leptinisa da lipidebs Soris
33
korelaciuri kavSiris gamokvlevis dros. WOSCOPS kvlevam aCvena insulinis
mimarT mgrZnobelobasa da leptins Soris mWidro kavSiri, smi-sgan
damoukideblad. rac SesaZloa xsnis im faqts, rom leptini gulis
koronaruli daavadebis damoukidebeli risk faqtoria[205].
Erik Ingelsson-ma da Tanaavt. gamoikvlies 362 pacienti, raTa ganesazRvraT
leptinis jvaredin-damokidebuleba kardiometabolur risk-faqtorebTan.
maTi Sedegebis Tanaxmad leptinis koncentracia mniSvnelovnad maRali iyo
qalebSi (P<0,0001). multivariabelur modelSi, leptini dadebiTad
korelirebda smi-YTan da welis garSemowerilobasTan. leptinis
koncentracia metaboluri sindromis komponentebis ricxvTan ufro maRali
iyo, vidre sxva adipokinebisa. am kvlevaSi gamovlinda leptinis korelacia
yvela gamokvleul maxasiaTebelTan, garda Tambaqos mwevelebisa. kvlevis
Tanaxmad, leptinis koncentracia izrdeboda metaboluri sindromis
komponentebis raodenobis zrdasTan erTad.
Wildman da Tanaavt. kvlevis Tanaxmad menopauzis mqonesaSualo asakis
qalebSi, leptinis gazrdili done asocirdeboda maRali simkvrivis
lipoproteinebis donis daqveiTebasTan da diastoluri wnevis, glukozis
donisa da insulinrezistentobis matebasTan [206]. msgavsi Sedegebi miiRes
Langenberg-ma da Tanaavtorebma. maTi grZelvadiani kvlevis Tanaxmad, leptini
asocirdeboda metaboluri sindromis umetes komponentebTan sawyis etapze;
Tumca,maTi kvlevis Tanaxmad leptinis aRniSnuli kavSiri metaboluri
sindromis komponentebTan, ar unda yofiliyo am drosganviTarebuli gulis
koronaruli daavadebiT sikvdilobis xelSemwyobi faqtori[207]. aseve,
arsebobs mtkicebuleba, rom leptinis kavSiri insulinrezistentobasTan ar
aris damokidebuli cximovan masaze [208, 209]. leptinsa da
insulinrezistentobas Soris arsebuli zusti meqanizmi da maTi
kompleqsuri urTierTdamokidebuleba sxva kardiometabolur risk-
faqtorebTan, bolomde naTeli ar aris [210].
Huang KCda Tanaavt. kvleva moicavda mozardebSi (diabetis gareSe) plazmis
leptinis kavSiris gamovlenas sxvadasxva anTropometrul maCveneblebTan,
34
smi-Tan, lipidebTan da insulinrezistentobasTan. maTMmier Catarebuli
kvlevis Tanaxmad, plazmis leptinis done mniSvnelovnad maRali iyo
gogonebSi (17.45+/-10.13 ng/ml) vaJebTan SedarebiT (8.81+/-6.71 ng/ml, P<0.001).
plazmis leptinis done dadebiTad korelirebda smi-Tan, welis
garSemowerilobasTan, weli/TeZos TanafardobasTan, cximovan masasTan,
cximovani masisprocentul maCvenebelTan da trigliceridebTan.
insulinrezistentobis indeqsi dadebiTad korelirebda smi-Tan, welis
garSemowerilobasTan, weli/TeZos TanafardobasTan, cximovan masasTan,
cximovani masis procentul maCvenebelTan, trigliceridebTan da leptinTan.
multivariaciuli xazobrivi regresiis modelis gamoyenebiT, aRmoCnda, rom
plazmis leptinis done mniSvnelovan kavSirSirCeba
insulinrezistentobasTan, Tundac mas Semdeg rac daregulirda asakisTvis,
sqesisTvis, smi, cximovani masisa da trigliceridebisTvis. kvlevidan
gamomdinare plazmis leptinis done SesaZloa metaboluri sindromis
darRvevebisa da kardiovaskuluri daavadebebis Camoyalibebis prediqtori
iyos [211].
arsebuli samecniero literatura, kvlevis Sedegebi bolomde ver
adasturebs leptinis mWidro korelacias metabolur sindromTan da mis
calkeul komponentebTan. aseve bolomde naTeli ar aris, leptinis, rogorc
kardiometaboluri darRvevis prediqtoris roli da is mosazreba, rom es
hormoni zrdis metaboluri darRvevebis risks. amas garda, gamoiTqva
mosazreba hiperleptinemiis, rogorc metaboluri sindromis axali
komponentis damatebisa da ganxilvis Taobaze. vinaidan arsebobs monacemebi
imis Taobaze, rom leptinis siWarbis mqone pirebs metaboluri sindromi
gacilebiT ufro adreul etapzeuviTardebaT.
taivanSi Catarda kvleva, romelSic ikvlevdnen leptinis korelacias
kardiometabolur risk-faqtorebTan da hiperleptinemias, rogorc
metaboluri sindromis prediqtors. kvlevaSi 957 adamiani monawileobda,
upiratesad mamakacebi. kvlevis Tanaxmad, leptinis done orive sqesSi
korelirebda gul-sisxlZarRvTa daavadebis gazrdil riskTan. uzmod
glukozis garda, leptinis momatebuli done asocirdeboda metaboluri
35
sindromis zrdasTan. asakis gaTvaliswinebis Semdeg, SeiniSneboda kavSiri
leptinis donesa da metabolur sindroms Soris. mxolod asakTan an
Tambaqos moxmarebis gaTvaliswinebis Semdeg, is pirebi visac aReniSneboda
leptinis ufro maRali done, yvelaze metad hqondaT gazrdili metaboluri
sindromis ganviTarebis riski. smi-is gaTvaliswinebis Semdegac metaboluri
sindromis riski kvlav mniSvnelovnad maRali rCeboda im mamakacebSi, visac
leptinis ufro maRali done aReniSneboda. kvlevis erT-erTi mniSvnelovani
Sedegi iyo daskvna, rom mamakacebsa da qalebSi leptinis gazrdili done
metaboluri sindromis prediqtoriiyo [211].
1.7. leptini da Zvlis mineraluri simkvrive
axlo warsulSi simsuqnesa da osteoporozs Soris kavSiri ar iyo cnobili,
Tumca uaxlesi kvlevebis Sedegad aRmoCnda, rom am or daavadebas aqvs rigi
saerTo genetikuri da garemo faqtorebi. arsebobs damadasturebeli masala,
rom sxeulis cximovani qsovili SesaZloa dadebiTad moqmedebdes Zvalze,
Tumca sapirispiro kvlevebis Sedegebi ar adasturebs cximovani qsovilis
Zvalze damcav efeqts [213].
cnobilia, rom motexilobis riskis saukeTeso ganmsazRvreli faqtori
Zvlovani qsovilis masaa, romelic izomeba Zvlis mineraluri simkvriviT
(Zms). mravalricxovani kvlevebi adasturebs, rom didi wona an maRali smi
dadebiT korelaciaSia Zms-sTan da rom wonis kleba Zvlis masis kargvas
iwvevs. aRniSnuli korelacia SeiniSneba, rogorc qalebSi, ise mamakacebSi,
aseve zrdasrulebSi, bavSvebsa da mozardebSi. mravalwliani kvlevebis
Sedegad dadginda, rom Zms-s cvlilebebi dadebiT korelaciaSia iyo
cximovani masis cvlilebasTan [215, 216]; aseve kvleva EPIC‐ma aCvena, rom im
pirebs, visTanac ufro “swrafad” mcirdeboda Zvlis simkvrive, hqondaT
mniSvnelovnad naklebi cximovani qsovilis masa,im pirebTan SedarebiT,
visTanac “nela” mimdinareobda Zvlis masis Semcireba [217]. Lau da
36
Tanaavtorebis Tanaxmad mamakacebs, romelTac aReniSneboda vertebruli
deformaciis mZime forma, hqondaT cximovani qsovilis gacilebiT dabali
Semcveloba, sakontrolo jgufTan SedarebiT [218].
aRniSnuli monacemebis sapirispirod, rigi kvlevebis Tanaxmad, cximovani
qsovili SesaZloa srulebiT ar moqmedebdes Zvlis masis damcavad. aziel
da kavkasiel qalebSi Catarebuli farTomasStaburi kvleviT, cximovani
qsovilis masa uaryofiTad korelirebda Zvlovan masasTan, rac miuTiTebda
Zvalze cximovani qsovilis uaryofiT gavlenaze. msgavsi Sedegi dadasturda
ramodenime farTomasStaburi kvleviTac [214].
Zms-sa da cximovan masas Soris uaryofiT kavSirze metyvelebs kvlevebi,
romlebSic Seswavlilia garemo faqtorebis da sxvadasxva medikamentebis
gavlena Zvlovan masaze. mag. cnobilia, rom fizikuri datvirTva zrdis
Zvlovan masas da paralelurad amcirebs cximovani qsovilis masas
[219].dadgenilia, rom kalciumiT mdidari sakvebi pubertatis asakSi zrdis
Zvlis pikur masas, xandazmulebSi amcirebs Zvlis danakargs da
motexilobis risks. amasTan erTad, kalciumi aumjobesebs wonisa da
cximovani qsovilis klebas, Tumca, amis dasadastureblad mravalwliani
kvlevebia saWiro [220]. menopauza aseve dakavSirebulia Zvlovani masis
gazrdil danakargebTan, cximovani masis zrdasTan da kunTuri masis
SemcirebasTan. aseve dadgenilia, rom medikamentebisrigi uaryofiTad
moqmedebs Zvlovan masaze da amasTan zrdis sxeulis masas mag:
gonadotropin-rilizing hormoni prostatis kibos mkurnalobisas, an
glukokortikoidebi [214].
aRniSnuli gansxvavebuliSedegebisavaraudod ganpirobebulia sxvadasxva
faqtoriT, rogoricaa sqesi, asaki, eTnikuriwarmomavloba, kvlevis dizaini,
analizis meTodebi da sxva.
arsebobs cximovani qsovilis Zvalze moqmedebis ramdenimesavaraudo
meqanizmi, romelic xsnis cximovan da Zvlovan qsovils Soris kavSirs. erT-
erTi aRniSnuli meqanizmi SesaZloa dakavSirebli iyos cximovan qsovilTan
da mis mier gamomuSavebul biologiurad aqtiur nivTierebebTan. leptini,
37
cximovani qsovilis mier gamomuSavebuli hormoni, SesaZloa monawileobdes
Zvlis metabolizmSi. amasTan,cnobilia, rom adipocitebi da osteoblastebi
erTi progenitorisgan viTardebian, mezenqimuri Rerovani ujredisgan; In vitro
kvlevebma gamoavlina, rom leptini SesaZloa pirdapir moqmedebdes Zvlis
tvinis mezenqimur Rerovan ujredebze, raTa gaaZlieros maTi diferenciacia
osteoblastebad da daTrgunos maTi diferenciacia adipocitebad.
diferenciaciis dros maT Soris balansi damokidebulia ramdenime
meqanizmze, ramac SesaZloa aseve gansazRvros cximovani qsovilis saboloo
zegavlena Zvalze [221].
leptinis Zvlis metabolizmze moqmedebis zusti meqanizmi bolomde
cnobili ar aris. literaturis monacemebi arasrulyofili da sadavoa.
savaraudod leptinis Zvalze moqmedeba xorcieldeba ori meqanizmiT. I
meqanizmi – “arapirdapiri”, SemoTavazebulia Ducy da Tanaavtorebis mier. am
meqanizmis mixedviT cximovani ujredebis mier gamomuSavebuli leptini
sisxlZarRvovani endoTeluri ujredis ObRa receptoris meSveobiT gadis
hematoencefalur bariers, sadac aaqtiurebs hipoTalamusis ObRb
receptors. es signalebi, Tavis mxriv, astimulireben e.w. HOBIF-is
(hipoTalamusis osteoblastebis mainhibirebeli faqtori) eqspresias.
gamomuSavebuli HOBIF aqveiTebs osteoblastebis matriqs-warmomqmnel
unars. am avtorebma aRmoaCines didi wonis mqone Ob(Lep)-/- virTagvebSi
anomaliurad didi Zvlovani masis savaraudo mizezi. kerZod gamoavlines,
rom leptinis intracerebroventrikuluri ineqciebi iwvevda Zvlovani masis
Semcirebas. aqedan gamomdinare, Ducy da Tanaavtorebis varaudiT leptini
astimulirebs tvinSiHOBIF-is gamomuSavebas.
aRniSnul meqanizmSi CarTuli meore centraluri rgoli aris NPY da
misiY2 receptori, romelsac, Tavis mxriv, SeuZlia HOBIF-is
stimulacia.NPYaris hipoTalamusis mier gamomuSavebuli peptidi, romelic
sakvebis miRebas, energiis homeostazs da Zvlis remodelirebas
aregulirebs. leptini ainhibirebs NPYgenis eqspresias hipoTalamusSi.
plazmis leptinis daqveiTeba aZlierebs NPYeqspresias, astimulirebs
38
sakvebis miRebas, ainhibirebs energiis danaxarjs da xels uwyobs simsuqnisa
da masTan dakavSirebuli fenotipis ganviTarebas. NPY‐is efeqti
regulirdeba Y‐ receptoruli sistemiT, romelic eqspresirdeba
hipoTalamusSi da Sedgeba 5 gansxvavebuli receptorisgan (Y1, Y2, Y4, Y5,
Y6).CamoTvlilTagan yvelaze ukeT Seswavlilia Y2 receptori.
hipoTalamusSi NPY2 deficitis mqone virTagvebs aReniSnebodaT
momatebuli Zvlovani masa, maSin roca amis gamomwvevi sxva endokrinuli
mizezi ar arsebobda. aRniSnuli miuTiTebs, rom es receptorebi
aregulireben Zvlis homeostazs avtonomiuri funqciis Secvlis gziT.
amgvarad, Y2 an leptinis, arqona aqveiTebs HOBIF–s da aZlierebs
osteoblastebis produqcias. Elefteriou et al. aRmoaCines, rom NPY-deficitis
mqone virTagvebs aReniSnebodaT Zvlis normaluri masa, gansxvavebiT NPY2-
deficitis mqone virTagvebisgan. aseve gamovlinda, rom NPY4-deficitis
mqone virTagvebs aReniSnebaT Zvlis normaluri masa, maSin rocaNPY2 da
NPY4-is erTdrouli gamoTiSva mniSvnelovnad zrdis Zvlovan masas,
mxolod NPY2-deficitis mqone virTagvebTan SedarebiT. Zvlis
gaZlierebuli formireba NPY2 da NPY4-s erTdrouli gaTiSvis SemTxvevaSi
miuTiTebs NPY2 da NPY4-s receptorul gzebs Soris sinergiul
damokidebulebaze [214].
amasTan, simsuqneze leptinis moqmedeba ganpirobebulia im neironuli
gzebiT, romelic moicavs proopiomelanokortiniT (pomk) warmodgenil
katabolur gzebs. leptini astimulirebs pomk neironebs raTa gamomuSavdes
α-melanokortin mastimulirebeli hormoni (α-mmh).α-mmh-is da melanokortin
3da 4-is kombinacia iwvevs sakvebis naklebi raodenobiT miRebas da energiis
danaxarjis gazrdas. amasTan, leptini ainhibirebsAgRP‐is(agouti‐related
protein)aqtivobas, romelic aris melanokortin 3 da 4-is receptoris
endogenuri antagonisti. yovelive amis Sedegad izrdeba melanokortin 3 da
4-is receptoris signali da mcirdeba mada. simsuqneze zemoqmedebis garda,
melanokortin-sasignalo gza SesaZloa iwvevdes Zvlis rezorbcias da ara
39
formirebas. Mc4r gaTiSuli Tagvebi avlenen Zvlis did masas Zvlis
rezorbciis Semcirebis xarjze [222].
II meqanizmi – “pirdapiri”anu osteotrofuli efeqti - gulisxmobs
Rerovani ujredebidan osteoblastebis diferenciaciisTvis xelis
Sewyobasa da osteoklastebis warmoqmnis daTrgunvas. leptini
astimulirebs IGF-1-is (Insulin‐like growth factor‐1)produqcias, romelic, Tavis
mxriv, axdens: a) osteoblastebis proliferaciis stimulacias, ris
Sedegadac izrdeba osteoblasturi xazis ujredebis mdgradoba
apoptozisadmi; b) osteoklastebis warmoqmnis supresias, osteoblastebis
Rerovani ujredebidan naklebi RANKL-is (NF-kappaB Ligand) warmoqmnis
Sedegad; g) OPG (Osteoprotegerin) stimulacias, romelic iwvevs
osteoklastebis supresias.
amgvarad, leptini Zvlis remodelirebis mniSvnelovani regulatoria. misi
gavlena Zvalze kompleqsuria. kerZod, adamianebSi Catarebul kvlevebSi
miRebulia rogorc uaryofiTi, aseve dadebiTi kavSiri leptinsa da Zms-s
Soris an leptinis gavlena Zvlovan qsovilze srulebiT ar vlindeba.
1.8. kvebis sxvadasxvastilis gavlena leptinze
arsebobs mosazreba, rom trigliceridebis maRali done iwvevs leptinis
gadaadgilebis dabrkolebas hematoencefaluri barieris gavliT[223].
saintereso iqneboda imis gamokvleva, Tu ra Sedegi eqneboda
trigliceridebis donis daqveiTebas. Teoriulad aRar dabrkoldeboda
leptinis transporti hipoTalamusamde, Sesabamisad moxdeboda wonis
daregulireba madis daTrgunvis da energiis danaxarjis gazrdis Sedegad.
aRniSnulidan gamomdinare gadavwyviteT gagvesazRvra naxSirwylebis da
cximebis SezRudvis gavlena trigliceridebis doneze da Sesabamisad
leptinis koncentraciaze simsuqnis mqone pacientebSi. Catarebulma in
vivokvlevebma virTagvebze, aCvena, rom rZem, sadac cximis 98%
trigliceridebis saxiT iyo warmodgenili, dauyovnebliv Seaferxa
40
leptinis gadasvla sisxlidan tvinSi. msgavsi Sedegi ar dafiqsirebula
ucximo rZis miRebis SemTxvevaSi. aseve ar gamovlenila msgavsi efeqti
soios cximis miRebis Semdeg, rac gvafiqrebinebs imas, rom mcenareul
trigliceridebs da esenciur Tavisufal cximovan mJavebs aseve ar aqvT
leptinis transportirebis Seferxebis unari [224].
milanis universitetSi Catarebuli kvlevis Tanaxmad leptinis done
mniSvnelovnad Semcirda dabalkaloriuli dietis, fizikuri datvirTvis da
Sesabamisad wonis klebisa da smi-is daqveiTebis Sedegad. meore kvlevis
Tanaxmadac, sxeulis 10%-iT daqveiTebam - leptinis donis TiTqmis 50%-iT
Semcireba gamoiwvia. msgavsi saxis kvlevebi mravalia da Sedegebic msgavsia.
leptinis Semcireba xdeba rogorc cximebis ise naxSirwylebis SezRudvis
xarjze. Tundac normaluri wonis mqone pacientebSi, leptinis done
izrdeba cximiani sakvebis didi raodenobiT miRebis fonze, xolo
SezRudvis SemTxvevaSi ki - qveiTdeba [225].
Tavi 2: gamokvlevis masalebi da meTodebi
2.1. gamokvlevis masalis zogadi daxasiaTeba
kvleva mimdinareobda S.p.s. “janmrTeli cxovreba”-s (amJamad S.p.s.
“endokrinologiis erovnuli instituti” –s saxeliT cnobili) bazaze 2009
wlis ivnisidan 2010 wlis dekembris CaTvliT.
41
CarTvis kriteriumi iyo: mdedrobiTi sqesi, asaki ≥ 20 welze, kvlevaSi
monawileobaze Tanxmoba, dadasturebuli xelmoweriT. gamoricxvis
kriteriumebs warmoadgenda: asaki < 20 welze, anamnezSi iseTi qronikuli
daavadebis arseboba, romelic imoqmedebda maT metabolur funqciebze, mag:
farisebri jirkvlis funqciis darRveva, qronikuli hepatiti, cirozi,
hipoTalamusis daavadebebi, Saqriani diabetis dadasturebuli diagnozi;
kvlevaSi ar erTvebodnen pacientebi, vinc kvlevis dawyebamde 6 Tvis adre
imyofeboda dabalkaloriul dietaze (<1800 kkal) an mkurnalobda simsuqnis
sawinaaRmdego farmakologiuri preparatebiT, an itarebda metabolizmze
mmoqmed sxva mkurnalobas, an Catarebuli hqonda bariatriuli qirurgiuli
Careva.aseve kvlevidan gamoricxvis kriteriums warmoadgenda orsuloba da
laqtacia. TiToeuli pacienti, vinc akmayofilebda kvlevaSi CarTvis
kriteriumebs da ar aReniSneboda kvlevidan gamoricxvis kriteriumi avsebda
specializirebul kiTxvars; pacienti iyo uzmod gamokvlevebis dawyebamde
minimum 10 saaTis manZilze; maT utardeboda fizikuri gamokvleva da venuri
sisxlis nimuSis aReba Semdeg maCveneblebze: Sratis leptini, bazaluri da
postprandialuri insulini, glukozisadmi tolerantobis gansazRvris
testi, lipiduri speqtri (saerTo qolesterini, trigliceridebi, maRali
simkvrivis lipoproteinebi da dabali simkvrivis lipoproteinebi). venuri
sisxlis aRebis maqsimaluri dro iyo 11:00. yvela pacients Cautarda
ormagenergetikuli rentgenuli absorbciometriiT sxeulis agebulebis
gansazRvra.
kvlevis pirobebi daakmayofila 149 pacientma, romelTaasakobrivi zRvari
20-70 wlamde meryeobda.
2.2. kvlevis kiTxvari:
pacientebis gamokiTxva xdeboda specialuri kiTxvaris saSualebiT.
kiTxvari iyo martivi, ise rom pacients Tavad SeeZlo misi Sevseba. kiTxari
Sedgeboda 1 gverdis da 10 kiTxvisgan. kiTxvaris mizani iyoSemdegi saxis
informacis miReba: demografiuli (mag: asaki, sqesi da a.S.), cxovrebis
stili (mag: Tambaqo, alkoholi, sxva mavne Cvevebi da a.S.), daavadebis
42
anamnezi da medikamentebi, fiziologiuri statusi (orsuloba, laqtacia,
uzmod yofnis periodi da a.S.).
2.3. fizikaluri gamokvleva:
2.3.1. sasicocxlo maCveneblebis (arteriuli wneva, pulsi)gansazRvra:
arteriuli wnevis gansazRvramde pacientiminimum 5 wuTi imyofeboda
mjdomare, mosvenebul mdgomareobaSi. pacients esazRvreboda wneva orive
xelze, daaxloebiT 2 wuTis intervaliT. kvlevisTvis irCeoda dominanturi
xeli. dominantur xelze pacients damatebiT esazRvreboda wneva 2-jer, 2
wuTiani intervalis dacviT. kvlevisTvis viyenebdiT sami gazomviT miRebul
saSualo ariTmetikul cifrs. arteriuli wnevis gasazomad viyenebdiT
avtomatur spigmomanometrs – Microlife BPA80. pacients pulsi esazRvreboda 1
wuTis manZilze.
2.3.2. wona, simaRle, sxeulis masis indeqsi, welis garSemoweriloba:
pacientebis awonva da simaRlis gansazRvra xdeboda fexsacmelebis,
qurTukisa da mZime tanisamosis gareSe. pacientebis asawonad viyenebdiT
saswors – ТВЕС; wonis sazom erTeulad viyenebdiTkilogramebs (kg).
sasworis awonvis maqsimaluri zRvari a 200 kg-s Seadgend. simaRlis
gansazRvrisTvis viyenebdiT simaRlis meqanikur sazoms – Seca 240; simaRlis
sazom erTeulad viyenebdiT metrs (m). sxeulis masis indeqsis (smi) (Quetelet
indeqss) gamosaTvlelad viyenebdiT formulas (226): wona (kg)/simaRlis² (m²).
smi-is mixedviT gamovyaviT sami jgufi. jgufebi ixileT cxrilSi #1.
cxrili #1
jgufi s.m.i.-is maCvenebeli maxasiaTebeli
I 18.5 – 24.9 normaluri wona
II 25 – 29.9 Warbi wona
III > 30 simsuqne
43
welis garSemowerilobas vsazRvravdiT TeZos Zvlis wvetebsa da me-12 neknis
qvemo sazRvars Soris Sua wertilSi. welis garSemowerilobis sazom
erTeulad viyenebdiT sm-s. jandacvis saerTaSoriso organizaciis
monacemebis Tanaxmad maRali welis garSemoweriloba asocirdeba
kardiometaboluri daavadebis gzrdil rikTan [212].
2.3.3. sxeuliskompoziciis gansazRvra:
sxeuliskompoziciis Seswavla da qsovilovani gadanawileba ganisazRvra
ormagenergetikuli rentgenuli absorbciometriiT (DXA). DXA-smeSveobiT
isazRvreba sxeulis cximovani, kunTovani da Zvlovani masa.DXA
dafuZnebulia rentgenis orfotoniani sxivis absorbciometriis
principze.Zvlis mineraluri simkvrivis Sefaseba warmoebs welis malebSi,
proqsimalur barZaySi, winamxarSi.gamokvlevis Casatareblad viyenebdiT
Lunar Prodigy Primo, General Electric, 2008.
2.4. venuri sisxlis nimuSi:
venuri sisxlis nimuSis aReba xdeboda 10-12 saaTis SimSilis Semdeg dilis
9:00-11:00 saaTis SualedSi; aRebuli nimuSis nawili inaxeboda 4ºC-ze.
TiToeuli pacientisTvis vsazRvravdiT saerTo qolesterinis (qol.),
trigliceridebis (tg), maRali simkvrivis lipoprotein-qolesterinis (msl),
dabali simkvrivis lipoprotein-qolesterinis (dsl), uzmod glukozis,
Sratis leptinis, bazaluri insulinisdones.xdeboda insulinrezistentobis
indeqsis (HOMA‐IR) gamoTvla Semdegi formuliT: uzmod bazaluri insulinis
done (mU/mL) + uzmod plazmis glukoza (mmol/L) gayofili 22,5 [227].
venuri sisxlis nimuSis aRebis Semdeg, pacientebs utardeboda glukozis
mimarT tolerantobis gansazRvris testi (gtt). testis dawyebidan 2 saaTSi
44
kidev erTxel viRebdiT venuri sisxlis nimuSs postprandialuri insulinis
gansazRvrisTvis, romelsac vinaxavdiT 4ºC-ze.
glukozis gansazRvrisTvis viyenebdiTglukozooqsidazur meTods.
glukozis sazom erTeulad viyenebdiT mg/dl-s.
glukozisadmi tolerantobis gansazRvris testis Casatareblad 75 gr.
glukoza ixsneboda 200 mloTaxis temperaturis wyalSi da pacients is 5
wuTis manZilzeunda mieRo. Ddalevidan 2 saaTSi kvlav vsazRvravdiT
glukozis dones.Sedegebis interpretaciisTvis, viyenebdiT janmos
rekomendaciebs (cxrili #2) [228].
cxrili #2 gtotinterpretaciis janmos rekomendaciebi
maCvenebeli norma
(mg/dl)
normidan gadaxra
(mg/dl)
uzmod glukoza < 110 > 110
datvirTvidan 2 saaTSi < 140 > 140
lipiduri profili moicavda saerTo qolesterinis, trigliceridebis,
maRali simkvrivis lipoproteinebisa da dabali simkvrivis
lipoproteinebisgansazRvras. normisa da normidan gadaxris maCvenebeli
motanilia cxrilSi #3.
saerTo qolesterinis gansazRvrisaTvis viyenebdiT “CHOD-PAP” meTods
(qolesterinis fermentuli kalorimetriuli testi lipidebis gamwmendi
faqtoriT [LCF]). am meTodis meSveobiT qolesterinis gansazRvra xdeboda
fermentuli hidrolizis da oqsidaciis Sedegad. indikatori yalibdeboda
wyalbadis peroqsidis da 4-aminofenazonisgan, fenolisa da peroqsidazis
Tanaarsebobisas. saerTo qolesterinis sazom erTeulad viyenebdiT mg/dl.
evropis aTerosklerozis asociaciis rekomendaciiT qolesterinis done
45
unda iyos < 200 mg/dl-ze. saerTo qolesterins vsazRvravdiT “human”-is
firmis “Cholesterol liquicolor”test nakrebiT.
trigliceridebs vsazRvravdiT “GPO-PAP” meTodiT (trigliceridebis
fermentuli kalorimetriuli testi lipidebis gamwmendi faqtoriT [LCF]).
am meTodis meSveobiT trigliceridebis gansazRvra xdeboda lipaziT
fermentuli hidrolizis saSualebiT. indikatori yalibdeboda wyalbadis
peroqsidis, 4-aminoantipirinis da 4-qlorofenolidan peroqsidazis
katalizuri zemoqmedebis Sedegad. trigliceridebis sazom erTeulad
viyenebdiT mg/dl-s. (229). trigliceridebis dones vsazRvravdiT “human”-is
firmis “Triglycerides liquicolor –mono”test nakrebiT.
maRali simkvrivis lipoproteinebis gansazRvrisTvis viyenebdiT
“CHOLESTEROL liquicolor”test nakrebs. qilomikronebis, Zalian dabali
sikvrivis lipoproteinebis da dabali simkvrivis lipoproteinebisdaleqva
xdeboda fosforismJavis da magniumis qloridis damatebiT.
centrifugirebis Semdeg, siTxe Seicavda maRali simkvrivis
lipoproteinebis fraqciebs. msl-is sazom erTeulad viyenebdiT mg/dl-s.
dabali simkvrivis lipoproteinebis gamosaTvlelad viyenebdiT saerTo
qolsterinis, msl-is koncentraciisa da trigliceridebis koncentracias.
dsl-is gansazRvrisTvis viyenebdiT Friedewald et al. mier mowodebul formulas
[229]: qolesterini (mg/dl) – trigliceridebi (mg/dl)/5 - maRali simkvrivis
lipoproteinebi (mg/dl). mis sazom erTeulad aseve viyenebdiT mg/dl-s.
cxrili # 3: lipiduri profilis norma da darRveva
norma (mg/dl) normidan gadaxra
(mg/dl)
saerTo
qolesterini
< 200 > 200
trigliceridebi < 150 > 150
46
maRali simkvrivis
lipoproteinebi
> 40 mamakacebisTvis
> 50 qalebisTvis
< 40 mamakacebisTvis
< 50 qalebisTvis
dabali simkvrivis
lipoproteinebi
< 100 > 100
bioqimiuri analizebi Sesrulda germanuli warmoebis “humani”s fotometrze
Humalizer 2000.
Sratis leptinis dones vsazRvravdiT DRG firmis ELISA nakrebiT, rac aris
fermentiT moniSnuli imunosorbentuli kvleva dafuZnebuli sendviCis
principze.kvlevis arsi SemdegSimdgomareobs: mikrosinjara ifareba
monoklonuri antisxeuliT, romelic mimarTulia leptinis molekulis
antigenuri ubnisken. Semdeg isxmeva pacientis sisxlis nimuSi, romelsac
emateba is koniugatis xsnari, romelic Seicavs fermentiT moniSnul
antisxeuls. Sedegad warmoiqmneba sendviC-kompleqsi.mikrosinjaris
gamorecxvis Semdeg rCeba mxolod SekavSirebuli leptini. substratis
dasxmis Semdeg miRebuli Seferilobis intensivoba pirdapirproporciulia
pacientis sisxlis SratSi leptinis koncentraciisa. leptinis sazom
erTeulad viyenebdiT ng/ml-s.
Sratis insulinis dones vsazRvravdiT DRG firmis ELISA nakrebiT, rac
aris fermentiT moniSnuli imunosorbentuli kvleva dafuZnebuli sendviCis
principze.kvlevis arsi SemdegSmdgomareobs: mikrosinjara ifareba
monoklonuri antisxeuliT, romelic mimarTulia insulinis molekulis
antigenuri ubnisken. Semdeg isxmeva pacientis sisxlis nimuSi, romelsac
emateba is koniugatis xsnari, romelic Seicavs fermentiT moniSnul
antisxeuls, romelic aris anti-insulinuri antisxeuli, koniugirebuli
biotinTan. Sedegad warmoiqmneba sendviC-kompleqsi.mikrosinjaris
gamorecxvis Semdeg rCeba mxolod SekavSirebuli koniugati. meore
inkubaciuri safexuris dros, streptavidin peroqsidazis fermentuli
kompleqsi ukavSirdeba biotin-anti-insulinur antisxeulebs. SekavSirebuli
47
kompleqsis raodenoba proporciulia nimuSSi insulinis
koncentraciisa.substratis dasxmis Semdeg miRebuli Seferilobis
intensivoba pirdapirproporciulia pacientis sisxlis SratSi insulinis
koncentraciisa.insulinis sazom erTeulad viyenebdiT mU/L-s (merT/l).
cxrili #4
norma (μIU/ml) Hhiperinsulinemia(mU/L)
bazaluri insulini < 12,5 > 12,5
postprandialuriinsulin < 25 > 25
yvela hormonuli kvleva Catarebulia humanis warmoebis aparatze – ELISYS
UNO.
2.5. pacientebis ganawileba jgufebad
pacintebis jgufebad ganawileba moxda ori parametris mixedviT:
1. sxeulis masis indeqsi; da
2. asaki.
aRniSnulidan gamomdinare, smi-is mixedviT pacientebis dayofa moxda sam
jgufad:
I jgufi – pacientebi normaluri woniT (smi 18.5 – 24.9 kg/m2);
II jgufi – pacientebi Warbi woniT (smi 25 – 29.9 kg/m2);
III jgufi – pacientebi simsuqniT (smi> 30 kg/m2).
asakis mixedviT pacientebis ganawileba moxda or jgufad:
I jgufi – pacientebi 20-39 wlis asakiT;
II jgufi – pacientebi 40-70 wlis asakiT.
48
yvela pacients ganesazRvra zemoxsenebuli maCveneblebi, romelic Semdeg
damuSavda jgufebis mixedviT.
2.6. dietoTerapiis zegavlena leptinis doneze
arsebobsmonacemebi, rom trigliceridebis maRali done iwvevs leptinis
gadaadgilebis dabrkolebas hematoencefaluri barieris gavliT.
saintereso iqneboda imis gamokvleva, Tu ra Sedegi eqneboda
trigliceridebis donis daqveiTebas. Teoriulad aRarunda
dabrkolebuliyo leptinis transporti hipoTalamusamde, Sesabamisad
moxdeboda wonis daregulireba madis daTrgunvis da energiis danaxarjis
gazrdis Sedegad.aRniSnulidan gamomdinare gadavwyviteT gagvesazRvra
naxSirwylebis da cximebis SezRudvis gavlena trigliceridebis doneze da
Sesabamisad leptinis koncentraciaze, simsuqnis mqone pacientebSi.
sub-kvlevaSi CarTvis kriteriums warmoadgenda pacientis Tanxmoba,
bolomde mieRo monawileoba kvlevaSi, mdedrobiTi sqesi, simsuqne,
trigliceridebis done >151 mg/dl da <500 mg/dl da uzmod glikemia <110
mg/dl. gamoricxvis kriteriums warmoadgenda wina 6 Tvis manZilze
dabalkaloriuli dietiT mkurnaloba, Saqris damwevi, lipidebis
damaqveiTebeli an/da sxva metabolizmze moqmedi preparatebis moxamreba,
anamnezSi kvlevis dawyebamde 6 Tvis manZilze.
44 pacienti randomulad ganawilda or jgufSi. pacientTa asaki meryeobda
23-dan 48 wlamde. pirveli jgufi iRebda naxSirwylebiT Rarib dietas,
xolo meore jgufi – cximebiT Rarib dietas. kvlevis xangrZlivobam 12
kvira Seadgina. TiToeul jgufs, rogorc kvlevis dawyebis, ise 12 kviris
TavzeganesazRvra Semdegi parametrebi: wona, smi, trigliceridebis done,
Sratis leptinis koncentracia.
TiToeuli pacientisaTvis SemuSavdaindividualuri dieta im jgufisTvis
damaxasiaTebeli Taviseburebebis gaTvaliswinebiT, romelSic isini
49
randomulad iyvnenganawilebulebi.kaloraJis mxriv SezRudva ar
dawesebula.
pirveli jgufi iRebda energiis 60%-s cximebis, 30%-s cilebis da 10%-s
naxSirwylebis gziT.
meore jgufSi energiis 20% miReba xdeboda cilebiT, 25% cximiT, xolo 55%
naxSirwylebiT. aseve mkacrad iyo gansazRvruli, rom aRniSnul jgufSi
najeri cximebi yofiliyo <10%-ze da miRebuli qolesterinis raodenoba <
300 mg-ze.
2.7. masalis statistikuri analizi:
monacemebis mowodeba moxda saSualo±standartuli gadaxriT (sd) mudmivi
variabelisaTvis da n (%)variabelisaTvis. klinikuri maxasiaTeblebis
Sedareba xdeboda erTgzis ANOVA-Ti mudmivi variabelisaTvis da Chi‐sqaure
anFisher-is zusti testi variabelisaTvis. Spearman-is korelaciiT
ganvsazRvreTkavSiri leptinis donesa da kardiometabolur risk-faqtorebs
Soris.variabelobis analizis (ANOVA) gamoyenebiT moxda kvebis sxvadasxva
stilis (naxSirwylebis da cximebis SezRudva) gavlenis Seswavla wonis
klebaze, trigliceridebisa da leptinis doneze, kvlevis dawyebisa da 12
kviris Tavze.statistikuri analizisTvis gamoviyeneT SPSS 20.0 versia (SPSS,
Inc., Chicago, IL). P‐value < 0.05 iqna gamoyenebuli, rogorc statistikurad
sarwmuno.
50
Tavi 3: gamokvlevis Sedegebi
kvlevaSi CaerTo 149mdedrobiTi sqesis pacienti.
kvlevaSi CarTuli pirebis saerTo maxasiaTeblebida standartuli gadaxra
mocemulia cxrilSi #: 5.
cxrili #:5 saerTo populaciis daxasiaTeba
sakvlevi komponentebi saerTo populacia
n = 149
asaki (weli) 31.58 ± 10.37
51
wona (kg) 87.78 ± 17.2
simaRle (sm) 165.9 ± 5.7
smi (kg/m2) 31.86 ± 6.39
welis garS. (sm) 102.52 ± 18.31
sistoluri wneva
(mm.vwy.sv)
124.39 ± 12.67
diastoluri wneva
(mm.vwy.sv)
81.48 ± 10.78
leptini (ng/ml) 67.76 ± 31.71
insulin(merT/l) 13.87 ± 7.83
glukoza (mg/dl) 93.47 ± 10.10
HOMA‐IR 3.27 ± 2.2
saerTo qolest.(mg/dl) 206.14 ± 20.6
trigliceridebi (mg/dl) 195.42 ± 22.75
HDL‐C (mg/dl) 69.89 ± 4.59
LDL‐C (mg/dl) 105.17 ± 10.64
cximi% 47.34 ± 6.62
cximi (kg) 39.97 ± 11.93
ara-cximov. qs. (kg) 42.97 ± 6.35
Zvlovani masa (kg) 2.91 ± 0.41
zeda kidurebi (kg) 43.85 ± 7.38
qveda kidurebi (kg) 50.12 ± 7.41
torsi (kg) 48.24 ± 6.88
androiduli (kg) 52.21 ± 7.62
ginoiduri (kg) 53.11 ± 5.86
smi-is mixedviT dayofil jgufebSi pacientebi ganawilda Semdegnairad:
I jgufi (normaluri wonis mqone pacientebi – smi 18.5 – 24.9 kg/m2) –N - 19
(12.7%); II jgufi (Warbi wonis mqone pacientebi - smi 25 – 29.9 kg/m2) – N - 41
(27.52%); III jgufi (simsuqnis mqone pacientebi - smi> 30 kg/m2) –N - 89 (59.7%)
(ix. grafiki #1).
grafiki #1: pacientebis ganawileba jgufebad smi-is mixedviT.
52
53
ganisazRvra leptinis korelacia yvela sakvlev maxasiaTebelTan, rogorc
sakvlev populaciaSi, ise dayofil jgufebSi. saSualo maCveneblebi da
standartuli gadaxra mocemulia cxrilSi #6.
cxrili #6: saSualo da standartuli gadaxra smi-is mixedviT Seqmnil
jgufebSi:
sakvlevi komponentebi Ijgufi
(normaluri
wona)
n = 19
IIjgufi
(Warbi wona)
n = 41
IIIjgufi
(simsuqne)
n = 89
asaki (weli) 25.32 ± 5.49 29 ± 7.48 34.11 ± 11.45
wona (kg) 63.51 ± 6.84 77.62 ± 6.15 97.65 ± 14.04
simaRle (sm) 166.21 ± 5.93 167.68 ± 5.18 165.01 ± 5.74
smi (kg/m2) 22.57 ± 1.39 27.5 ± 1.52 35.86 ± 4.86
welis garS. (sm) 75.74 ± 8.25 92.78 ± 8.65 112.72 ± 14.54
sistoluri wneva
(mm.vwy.sv)
113.68 ± 5.74 117.93 ± 8.73 129.65 ± 12.5
diastoluri wneva
(mm.vwy.sv)
71.84 ± 6.5 76.32 ± 8.28 85.91 ± 10.16
leptini(ng/ml) 67.74 ± 29.35 54.38 ± 27.89 80.84 ± 26.05
insulini(merT/l) 9.51 ± 4.54 12.48 ± 4.67 15.09 ± 8.91
glukoza(mg/dl) 89 ± 7.22 93.80 ± 8.82 94.27 ± 10.97
HOMA‐IR 2.07 ± 0.99 2.9 ± 1.13 3.6 ± 2.56
saerTo qolest.(mg/dl) 199.57 ± 15.29 200.88 ± 14.98 209.97 ± 22.95
54
trigliceridebi(mg/dl) 168.13 ± 18.68 190.47 ± 25.31 213.25 ± 21.68
HDL‐C (mg/dl) 70.52 ± 4.49 69.49 ± 4.55 69.93 ± 4.66
LDL‐C (mg/dl) 101.74 ± 10.76 102.67 ± 11.92 107.08 ± 9.64
cximi% 37.95 ± 5.86 43.57 ± 4.58 51.12 ± 4.12
cximi (kg) 22.90 ± 4.8 32.01 ± 5.09 47.37 ± 8.66
ara-cximov. qs. (kg) 37.15 ± 4.47 41.18 ± 3.43 45.06 ± 6.73
Zvlovani masa (kg) 2.76 ± 0.44 2.38 ± 0.34 2.02 ± 0.37
zeda kidurebi (kg) 34.51 ± 6.97 39.9 ± 5.27 47.71 ± 5.27
qveda kidurebi (kg) 41.52 ± 7.55 46.15 ± 5.41 53.83 ± 5.48
torsi (kg) 38.29 ± 5.88 44.74 ± 5.33 52.01 ± 4.25
androiduli (kg) 41.43 ± 7.35 48.33 ± 6.11 56.35 ± 4.48
ginoiduri (kg) 46.63 ± 5.46 50.14 ± 4.37 55.90 ± 4.69
srulsakvlev populaciaSi leptinis statistikurad mniSvnelovani dadebiTi
korelacia aRiniSna wonasTan, smi-Tan, welis garSemowerilobasTan,
sistolur da diastolur wnevasTan, trigliceridebis da dabali
simkvrivis lipoprotein-qolesterinis donesTan,cximovani masis procentTan,
cximis raodenobasTan zeda da qveda kidurebsa da torsSi, (grafiki #2).
grafiki #2: srul sakvlev populaciaSileptinis dadebiTi korelacia - smi
(r=0.53, p<0.001), wona (r=0.49, p<0.001), welis garSemoweriloba (r=0.47, p<0.001),
saerTo cximis procenti (r=0.55, p<0.001), sistoluri da diastoluri wneva
(r=0.36, p<0.001 da r=0.3, p<0.001), trigliceridebida dabali simkvrivis
lipoprotein-qolseterini (r=0.09, p<0.05 da r=0.23, p<0.01).
korelaciuri kavSiri Seicvala jgufebis mixedviT.
I jgufSi leptinis dadebiTi korelacia darCa sistolur arteriul
wnevasTan, uzmod glikemiasa da cximovani masis procentul maCvenebelTan.
grafiki 3: leptinis dadebiTi korelacia normaluri wonis mqone
pacientebis jgufSi. pacientebis jgufSi, normaluri woniT, leptinis
dadebiTi korelacia aRiniSneboda sistolur wnevasTan (r=0.58, p<0.001),
Zvlis mineralur simkvrivesTan (r=0.14, p=0.05) saerTo cximis procentTan
55
(r=0.07, p=0.004), torsis (r=0.03, p=0.02) da androidul areSi Calagebul
cximovan masasTan (r=0.15, p=0.05).
II jgufSi leptinma dadebiTi korelacia aCvena mxolod smi-Tan, dabali
simkvrivis lipoprotein – qolesterinTan, trigliceridebTan, xolo
uaryofiTi korelacia ki - Zvlis mineralur simkvrivesTan.aseve dadebiTi
iyo leptinis korelacia cximis saerTo procentul SemcvelobasTan (r=0.2,
p=0.001), cximovani qsovilis masasTan (r=0.11, p=0.05), torsisa (r=0.19, p=0.05) da
androidul areSi Calagebul cximovan qsovilTan (r=0.18, p=0.05).
grafiki 4: leptinis korelacia Warbi wonis mqone pacientebis jgufSi.
Warbi wonis SemTxvevaSi, leptinis dadebiTi korelacia dafiqsirda
trigliceridebTan(r=0.17, p=0.05) da dabali simkvrivis lipoprotein-
qolesterinTan(r=0.37, p=0.02).
III jgufSi leptinis korelacia dadebiTi iyo wonasTan, smi-Tan,
trigliceridebTan, dabali simkvrivis lipoprotein - qolesterinTan,
cximovani masis procentTan, cximovani qsovilis saerTo masasTan, cximovan
qsovilTan zeda kidurebSi da torsis zonaSi da androidul zonaSi
Calagebul cximTan; gamovlinda leptinis uaryofiTi korelacia Zvlis
mineralur simkvrivesTan, racmeore jgufTan SedarebiT ufro metad iyo
gamoxatuli.
56
grafiki 5: leptinis korelacia simsuqnis mqone pacientebis jgufSi.
simsuqnis SemTxvevaSi, leptinis dadebiTi korelacia dafiqsirda smi-Tan
(r=0.22, p=0.04),trigliceridebTan(r=0.33, p=0.001), cximovani qsovilis saerTo
masasTan (r=0.25, p=0.001), cximovan qsovilTan zeda kidurebis (r=0.33, p<0.001),
torsis (r=0.22, p=0.03) da androidul nawilSi (r=0.31, p=0.003).
leptinis yvelaze dabali koncentracia iyo I jgufSi, xolo yvelaze
maRali – III jgufSi.
leptinis korelacia sakvlev maxasiaTeblebTan smi-is mixedviT dayofil
jgufebSi mocemulia cxrilSi #7
cxrili #7: leptinis korelacia sakvlev maxasiaTeblebTan smi-is mixedviT
dayofil jgufebSi (p < 0.05 ; p< 0.01**)
r
sakvlevi komponentebi Ijgufi
(normaluri
wona)
n = 19
IIjgufi
(Warbi wona)
n = 41
IIIjgufi
(simsuqne)
n = 89
asaki (weli) -0.43 0.03 -0.05
wona (kg) 0.26 0.08 0.39**
simaRle (sm) 0.14 -0.13 -0.05
57
58
smi (kg/m2) 0.19 0.28 0.22*
welis garS. (sm) 0.27 -0.02 0.17
sistoluri wneva
(mm.vwy.sv)
0.58** -0.08 0.14
diastoluri wneva
(mm.vwy.sv)
0.4 -0.17 0.07
insulini(merT/l) 0.13 -0.16 0.16
glukoza (mg/dl) 0.2 0.17 0.11
HOMA‐IR 0.05 -0.1 0.17
saerTo qolest.(mg/dl) -0.32 -0.12 -0.16
trigliceridebi(mg/dl) 0.31 0.17* 0.33**
HDL‐C (mg/dl) -0.13 0.27 0.27
LDL‐C (mg/dl) -0.29 0.37* 0.42**
cximi% 0.07* 0.2** 0.25**
cximi (kg) 0.48 0.11* 0.26**
ara-cximov. qs. (kg) -0.15 -0.27 0.04
Zvlovani masa (kg) 0.14* -0.07* -0.29**
zeda kidurebi (kg) 0.43 0.14 0.33**
qveda kidurebi (kg) 0.33 0.19 0.16
torsi (kg) 0.03* 0.19* 0.22*
androiduli (kg) 0.15* 0.18* 0.31*
ginoiduri (kg) 0.34 0.25 0.15
asakobrivi sxvaobis mixedviT jgufebi Semdegnairad ganawilda: 20-39 wlis
asaki – N - 119 qali; 40-70 wlis asaki – N - 30 qali (grafiki #6).
grafiki #6: pacientebis ganawileba asakis mixedviT.
saSualo maCveneblebi da standartuli gadaxra asakis mixedviT dayofili
jgufebisTvis mocemulia cxrilSi #3.
cxrili #8: saSualo da standartuli gadaxra asakis mixedviT dayofil
jgufebSi:
sakvlevi komponentebi Ijgufi
(asaki 20-39
weli)
n = 199
IIjgufi
(asaki 40-70
weli)
n = 30
asaki (weli) 27.34 ± 6 48.43 ± 5.86
59
60
wona (kg) 85.59 ± 16.99 96.48 ± 15.44
simaRle (sm) 166.11 ± 5.58 165.07 ± 6.19
smi (kg/m2) 30.98 ± 6.25 35.37 ± 5.80
welis garS. (sm) 100.13 ± 18.15 111.97 ± 15.97
sistoluri wneva
(mm.vwy.sv)
121.59 ± 10.61 135.5 ± 14.16
diastoluri wneva
(mm.vwy.sv)
79.33 ± 9.61 90 ± 11.06
leptini(ng/ml) 65.83 ± 31.49 75.43 ± 31.95
insulini(merT/l) 13.39 ± 7.45 15.72 ± 9.14
glukoza(mg/dl) 92.34 ± 9.04 97.93 ± 12.73
HOMA‐IR 3.05 ± 1.76 4.1 ± 3.34
saerTo qolest.(mg/dl) 203.04 ± 18.18 218.47 ± 24.98
trigliceridebi(mg/dl) 192.73 ± 21.77 206.08 ± 23.80
HDL‐C (mg/dl) 69.92 ± 4.69 69.75 ± 4.2
LDL‐C (mg/dl) 103.66 ± 10.79 111.1 ± 7.66
cximi% 47 ± 6.9 48.65 ± 5.3
cximi (kg) 38.78 ± 12.07 44.65 ± 10.25
ara-cximov. qs. (kg) 42.16 ± 6.17 46.17 ± 6.13
Zvlovani masa (kg) 2.90 ± 0.42 2.35 ± 0.36
zeda kidurebi (kg) 43.17 ± 7.45 46.54 ± 6.57
qveda kidurebi (kg) 50.02 ± 7.76 50.54 ± 5.94
torsi (kg) 47.83 ± 7.08 49.85 ± 5.87
androiduli (kg) 51.61 ± 7.67 54.61 ± 7.06
ginoiduri (kg) 53.21 ± 6.09 52.73 ± 4.97
aRniSnul or jgufs Soris leptinis done ufro maRali iyo II jgufSi.
Tumca, regresiuli analizis mixedviT asaki ar aRmoCnda leptinis
mniSvnelovaniganmsazRvreli faqtori.rodesacmoxda leptinis Seswavla
wonasTan mimarTebaSi, analizis Sedegad asaki dadebiT korelaciaSi
aRmoCnda wonasTan.
orive asakobriv jgufSi gamovlinda leptinis dadebiTi korelacia
wonasTan, smi-Tan, welis garSemowerilobasTan, saerTo cximovan masasTan.
amas garda, 20-39 wlis jgufSi leptinis dadebiTi korelacia damatebiT
aRiniSna sistolur da diastolur arteriul wnevasTan, uzmod
glukozasTan, dabali simkvrivis lipoprotein – qolesterinTan, Zvlovan
masasTan, xolo 40-70 wlis jgufSi – trigliceridebTan.
61
grafiki 7: leptinis korelacia 20-40 wlis asakisgan Sedgenil jgufSi.
aRniSnul jgufSi leptinis dadebiTi korelacia aRiniSna wonasTan (r=0.48,
p<0.001), smi-Tan (r=0.53, p<0.001), welis garSemowerilobasTan (r=0.45, p<0.001),
sistolur da diastolur wnevasTan pressure (r=0.37, p<0.001 da r=0.33, p<0.001,
Sesabamisad), uzmod glukozasTan(r=0.24, p=0.001), dabali simkvrivis
lipoprotein - qolesterinsa (r=0.21, p=0.02) da saerTo cximovani masis
procentTan(r=0.56, p<0.001).
grafiki 8: leptinis korelacia 40-70 wlis asakisgan Sedgenil jgufSi.
aRniSnul jgufSi leptinis dadebiTi korelacia aRiniSna wonasTan (r=0.47,
p=0.001), smi-Tan (r=0.48, p=0.001), welis garSemowerilobasTan (r=0.49, p=0.01),
trigliceridebsa (r=0.24, p<0.001) da saerTo cximovani masis procentTan
(r=0.48, p=0.01).
leptinis detaluri korelacia asakis mixedviT dayofil jgufebSi
mocemulia cxrilSi #9.
cxrili #9: leptinis korelacia sakvlev maxasiaTeblebTan asakis mixedviT
dayofil jgufebSi (p < 0.05 ; p< 0.01**)
r
sakvlevi komponentebi Ijgufi
(asaki 20-39
weli)
IIjgufi
(asaki 40-70
weli)
62
63
n = 199 n = 30
asaki (weli) 0.06 0.09
wona (kg) 0.48** 0.47**
simaRle (sm) -0.13 -0.02
smi (kg/m2) 0.53** 0.48**
welis garS. (sm) 0.45** 0.49**
sistoluri wneva
(mm.vwy.sv)
0.37** 0.26
diastoluri wneva
(mm.vwy.sv)
0.33** 0.12
insulini(merT/l) 0.13 0.33
glukoza (mg/dl) 0.24** 0.03
HOMA‐IR 0.16 0.29
saerTo qolest.(mg/dl) 0.01 -0.25
trigliceridebi(mg/dl) 0.09 0.24**
HDL‐C (mg/dl) 0.11 0.53
LDL‐C (mg/dl) 0.21* 0.2**
cximi% 0.56** 0.48**
cximi (kg) 0.54** 0.52**
ara-cximov. qs. (kg) 0.17 0.22
Zvlovani masa (kg) 0.25* -0.26**
64
zeda kidurebi (kg) 0.52** 0.57**
qveda kidurebi (kg) 0.49** 0.36*
torsi (kg) 0.55** 0.44**
androiduli (kg) 0.55** 0.51**
ginoiduri (kg) 0.49 0.16
gamovlinda uaryofiTi korelacia Sratis leptinsa da Zvlis mineralur
simkvrives Soris40-70 wlis asakis jgufSi. 20-39 wlis jgufSi leptinis
korelacia Zvlis mienralur simkvrivesTan iyo dadebiTi.mas Semdeg rac
gaviTvaliswineT asakis faqtori, smi da wona, kvlav SenarCunda aRniSnuli
uaryofiTi korelacia. korelacia gansakuTrebiT Zlieri iyo asakisa da smi-
is matebasTan erTad.
dietoTerapiisgavlena Sratis leptinis doneze:
sakvlevi populaciis sawyisi maxasiaTeblebi mocemulia cxrilSi 1.
cxrili #10: sakvlevi populaciis daxasiaTeba:
cximebiT Raribi
dieta
(n=22)
naxSirwylebiT
Raribi dieta
(n=22)
asaki (w) 33.2 ± 14.3 34.4 ± 11.2
wona (kg) 87.5 ± 19.3 86.9 ± 14.3
smi(kg/m2) 33.2 ± 5.2 34.6 ± 4.9
trigliceridebi
(mg/dl)
202± 51 199± 57
leptini(ng/ml) 78.84 ± 24.05 80.84 ± 19.05
12 kviris Semdeg dafiqsirda wonis mniSvnelovani kleba orive jgufSi,
Tumca naxSirwylebiT Raribi dietis dros wonis klebis intensivoba ufro
metad iyo gamoxatuli (-8.9 kg), cximis SezRudvasTan SedarebiT (-6.1 kg) (ix.
grafiki 9).
grafiki #9: naxSirwylebis an cximebis SezRudvis efeqti wonis (kg)
klebaze:
msgavsi Sedegi dafiqsirda trigliceridebis daqveiTebis mxriv
(naxSirwylebiT Raribi - (-37%) da cximebiT Raribi – (-21%) Sesabamisad)
(grafiki 10).
grafiki #10: naxSirwylebis an cximebis SezRudvis efeqti trigliceridebis
(mg/dl) donis daqveiTebaze:
65
rogorc mosalodneli iyo, kilogramebis ufro meti raodenobiT daklebis
SemTxvevaSi, leptinis donec metad daqveiTda naxSirwylebiT Raribi dietis
fonze da Seadgenda – (-32%), xolo cximebiT Raribi dietis fonze – (-19%).
(grafiki 11).
grafiki #11: naxSirwylebis an cximebis SezRudvis efeqti leptinis (ng/ml)
koncentraciis daqveiTebaze:
66
grafiki #12: leptinisa da trigliceridebis urTierTkavSiri:
67
68
Tavi 4: gamokvlevis Sedegebis ganxilva
aRniSnuli kvlevis mizani iyo Sratis leptinis korelaciis dadgena
kardiometaboluri daavadebis risk-faqtorebTan; aseve leptinis donis
Sedareba smi-sa da asakis mixedviT dayofil jgufebSi.
kvlevis monacemebis Tanaxmad, gamovlinda, rom leptinis koncentracia
yvelaze maRali iyo simsuqnis mqone pacientebis jgufSi, leptinis yvelaze
Zlieri dadebiTi korelacia aRiniSna rogorc mTeli sxeulis cximovan
masasTan, ise regionebis mixedviT dayofil cximovan masasTan,
gansakuTrebiT cximovani qsovilis ganawilebis androidul tipTan, misi
done izrdeboda asakTan erTad, igi dadebiTad korelirebda
trigliceridebTan. aseve gamovlinda, leptinis uaryofiTi korelacia Zvlis
mineralur simkvrivesTan.
Cveni kvlevis Tanaxmad leptinis done daqveiTda rogorc cximiT Raribi
dietis, ise naxSirwylebiT Raribi kvebis dros, Tumca am ukanasknelis
SemTxvevaSi leptinis daqveiTeba ufro mniSvnelovnad iyo gamoxatuli.
4.1. leptini, wona, smi da cximovani qsovili:
simsuqne aris disbalansi miRebul da gacemul energias Soris, rac
gamowveulia, umoZrao cxovrebis wesisa da gadaWarbebuli da
daubalansebeli kvebiTi Cvevebis urTierTkavSiriT. Sedegad izrdeba
cximovani qsovilis masa.
leptinis koncentracia yvelaze maRali iyo simsuqnis mqone pacientebis
jgufSi;Liuzzi A. da Tanaavtorebis, iseve rogorc Adami GF da Tanaavtorebis
mier Catarebuli kvlevebis monacemebi emTxveva Cvens mier miRebul Sedegebs
leptinis dadebiT korelaciasTan dakavSirebiT smi-Tan [231, 232].
69
leptinis genis eqspresia dakavSirebulia gacximovnebis xarisxTan, amitom
msoflioSi Catarebuli kvlevebis umetesoba amtkicebs leptinis dadebiT
korelacias smi-Tan da wonasTan.
simsuqne xasiaTdeba cximovani qsovilis gazrdili masiT, romelic
ganpirobebulia, adipocitis rogorc hipertrofiiT, aseve hiperplaziiT
[226]. saqarTveloSi pirvelad ganisazRvra korelacia smi-s, welis
garSemowerilobasa da leptins Soris. rogorc mosalodneli iyo leptinis
done pirdapir kavSirSi iyo smi-sa da welis garSemowerilobasTan.
rogorc mravali kvlevidan viciT, erTnairi smi-is mqone orive sqesis
warmomadgenlebSi - leptinis koncentracia ufro maRalia qalebSi,
mamakacebTan SedarebiT. es aixsneba cximovani qsovilis ufro meti
procentuli SemcvelobiT qalebSi da kanqveSa/visceraluri cximis ufro
maRali proporciuli TanafardobiT. Cveni kvlevis SezRudva iyo masSi
mxolod qalebis monawileoba, winaaRmdeg SemTxvevaSi zustad
ganvsazRvravdiT aris Tu ara sxvaoba qarTvel mamakacebsa da qalebs Soris
erTnairi smi-iT.
jer kidev 1998 wels Cas Lek Cesk-is mier daweril publikaciaSi aRniSnulia,
rom arsebobs dadebiTi korelacia smi-sa da leptinis dones Soris, rac
savaraudod aris leptinis produqciis an aRqmis unaris darRveva. amis gamo
leptinis egzogenuri Seyvana aseT SemTxvevebSi araefeqturia.
leptinis yvelaze Zlieri dadebiTi korelacia aRiniSna rogorc mTeli
sxeulis cximovan masasTan, ise regionebis mixedviT dayofil cximovan
masasTan, gansakuTrebiT androidul cximovan qsovilTan; wonasa da smi-Tan
korelaciis garda, Cven gamovikvlieT leptinis kavSiri cximovan masasTan,
cximisagan Tavisufal masasa da Zlovan masasTan. msgavsi detaluri
gamokvleva sakmaod mniSvnelovania. vinaidan smi mWidrod korelirebs
cximovan masasTan, Tumca am meTodiT ver xerxdeba kunTovani da cximovani
qsovilis gamoyofa. Cveni kvlevis farglebSi gamovikvlieT sxeulis
agebuleba DXA-Ti.marTaliaumniSvnelo, magram mainc gamovlinda
sxvaobacximis ganawilebis androidul da ginoidur models Soris.
70
pacientebis 50,8%-s aReniSneboda cximovani qsovilis ganawileba
androiduli tipiT, rac gulisxmobs cximis upiratesad muclis areSi
Calagebas; abdominuri simsuqne ki ufro metad aris dakavSirebuli
kardiometaboluri darRvevebis gazrdil riskTan.
Cveni kvlevis Sedegad leptini dadebiTad korelirebda cximovan
masasTan.korelacia ar gamovlinda leptinsa da kunTovan masas Soris.
msgavsi Sedegebi dafiqsirda García-Lorda P.da Tanaavt. mier Catarebul
kvlevaSic, romelic aseve mxolod qalTa populacias ikvlevda [233].
MehabirS.-isa da Tanaavt. mier Catarebuli kvlevis Tanaxmad
multivariaciuli analizis Sedegad gamovlinda, rom Warbi wonis mqone
qalebs leptinis koncentracia hqondaT 2-jer, xolo simsuqnis mqone qalebs
3-jer maRali, normalur smi-is mqone qalebTan SedarebiT. aRniSnulSi
cximovani masisCarTvis Semdeg, gairkva, rom rac ufro maRali iyo cximovani
qsovilis procentuli Semadgenloba, miT ufro maRali iyo leptinis done.
Cveni kvlevisgan gansxvavebiT MehabirS.-isa da Tanaavt. kvlevaSi
monawileobda mxolod aramweveli, postmenopauzis asakis qalebi [234].
Jurimae T.-sa da Tanaavtorebis kvlevaSic leptinma yvelaze Zlieri dadebiTi
korelacia gamoavlina sxeulis wonasa da smi-Tan. amasTan, simsuqnis mqone
pacientebSi cximovani qsovilis masa, gansakuTrebiT mxrebisa da bicefsebis
areSi mniSvnelovnad korelirebda leptinTan, rac ar dafiqsirda Cvens
kvlevaSi [235].
4.2. leptini da asaki:
Cven mier Catarebul kvlevaSi leptinis done izrdeboda asakTan erTad;
leptinis donis zrda asakTan erTad aseve aRiniSna Andreasson A.da
Tanaavtorebis mier Catarebul kvlevebSi [245].Cvens kvlevaSi leptinis
71
dadebiTi korelacia smi-Tan orive asakobriv jgufSi aRiniSna.msgavsi
Sedegebi aCvena aseve LoÈnnqvist Fda Tanaavt. kvlevamac[41].
Liuzzi Amier Catarebul kvlevaSileptinis done pirdapir korelirebda smi-
Tan da cximovan masasTan asakisa da sqesisgan damoukideblad.
asakis mateba dakavSirebulia iseT ujredul procesebTan, rogoricaa
oqsidaciuri stresi da anTeba, rac kidev ufro Zlierdeba simsuqnis
SemTxvevaSi.oqsidaciuri stresisa da anTebis mateba, Tavis mxriv, aRrmavebs
leptinis mimarT rezistentobas da iwvevs energiis homeostazis
disregulacias. Zhang G. da Tanaavt. mier virTagvebze Catarebuli kvlevebi
cxadyofs, rom asakis matebasTan erTad hopoTalamusis garkveuli“anTebiTi
gzebi” aqtiurdeba.rodesac moaxdines hipoTalamusis aRniSnuli “anTebiTi
gzebis”pirdapiri blokada, aRniSnulma virTagvebze “gamaaxalgazrdaveblad”
imoqmeda.gadaWarbebuli kveba zrdis hipoTalamusze endoTeliumis
retikulumis stress da Sesabamisad aaqtiurebs anTebiT IKKbeta/NF‐kappa B
gzebs, rac, Tavis mxriv, zrdis leptinis mimarT rezistentobas da simsuqnes
virTagvebSi. jerjerobiT ucnobia hipoTalamusze leptinis signalis
gaZliereba iwvevs Tu ara sicocxlis gaxangrZlivebazemsgavs cvlilebebs
[236].Aanalogiuri Sinaarsis kvlevebi adamianebze ar Catarebula, Tumca
leptinis mimarT rezistentoba SesaZloa marTlac warmoadgendes simsuqnesa
da asaks Soris kavSirs. Cveni kvlevis mier miRebuli Sedegi, asakis
matebasTan erTad leptinis koncentraciis mzardi xasiaTis sarwmuno
korelaciis Sesaxeb esadageba msoflioSi am mimarTulebiT Catarebul
sxvadasxva kvlevas. samwuxarod mocemuli kvlevis farglebSi ver
SeviswavleT leptinis donis koreqciisa da asakis korelacia.
4.3. leptini da trigliceridebis done;
imis gaTvaliswinebiT, rom leptini aregulirebs wonas, leptinis
darRveuli sinTezi, signali an mgrZnobeloba, Sesabamisad gamoiwvevs
energiis homeostazisa da sxeulis agebulebis mimarT garkveulgadaxrebs.
72
naTelia, rom hiperleptinemia simsuqnis gamoxatulebis maxasiaTebelia,
rogorc adamianebSi, ise cxovelebSi, rac aris leptinis mimarT
rezistentobis mizezi. magram xom ar aris hiperleptinemia hormonis is
saWiro done, romelic inarCunebs mis mgrZnobelobas da energiis
homeostazs?simsuqnismqone pirebis mxolod daaxloebiT 10%-s aReniSneba
leptini fiziologiur normebSi. miuxedavad amisa, leptinis mimarT
rezistentobis zusti meqanizmi kvlav ucnobia.
sxva kvlevebis msgavsad, Cvens kvlevaSic gamovlinda sakvlev populaciaSi
leptinis maRali mocirkulire done, rac miuTiTebs leptinis mimarT
rezistentobaze [237]. bunebrivia, rom vinaidan leptinis genis eqspresia
xdeba cximovan ujredebze, rac ufro metad iqneba gamoxatuli gacximovneba,
miT maRali iqneba leptinis koncentracia. Cvens kvlevaSi umetes pacients
aReniSneboda sawyisad leptinis sakmaod maRali koncentracia.aseve
gamovlinda hipertrigliceridemia, rac SesaZloa iyos axsna leptinis
momatebuli koncentraciisa; trigliceridebis momatebuli done Trgunavs
leptinis transports sisxlidan tvinamde da zrdis leptinis mimarT
rezistentobas. Cvens kvlevaSi rogorc naxSirwylebiT, ise cximebiT Rarib
kvebas hqonda kargi efeqti trigliceridebis da leptinis
daqveiTebaze.mocemuli kvlevis Sedegebi eTanxmeba Catarebul kvlevebs,
sadac aseve naCvenebia, rom trigliceridebis donis daqveiTebam TiTqmis
gaanaxevra mocirkulire leptinis done da gansakuTrebiT es kleba ufro
mniSvnelovani iyo naxSirwylebiT Raribi dietis fonze. sainteresoa is
faqti, rom cximovani cvlis maregulirebeli hormonis rezistentoba ukeT
qveiTdeba naxSirwylebis SezRudvis fonze. am fenomenis axsna, savaraudod
aris naxSirwylovani cvlis fonze wonis meti kleba, Sesabamisad meti
cximovani masis daqveiTeba da leptinis naklebi gamomuSaveba.
Cveni da kidev mravali kvlevis Tanaxmad leptinis done izrdeba wonis
matebasa da simsuqnesTan erTad.amis damamtkicebelia, normaluri wonis
mqone cxovelebisTvis leptinis egzogenuri Seyvanis sapasuxod aRniSnuli
wonis mateba.msgavsi Sedegi iqna miRebuli wonis deficitis mqone
adamianebTan leptinis egzogenuri Seyvanis Sedegad. aRniSnuli miuTiTebs
73
imaze, rom Tu ar aris darRveuli leptinis transporti hipoTalamusamde,
misi moqmedeba Tavisuflad xorcieldeba, rac realobaSi ar xdeba
simsuqnis mqone pacientebTan. simsuqne aseve dakavSirebulia
trigliceridebis maRal donesTan, rac leptinis signalis Semaferxebeli
SeiZleba gaxdes. naTelia, rom Tu moxdeba trigliceridebis daqveiTeba,
gaizrdeba leptinis mimarT mgrZnobeloba, leptini Seuferxeblad
Seasrulebs mis anti-simsuqnis hormonis funqcias da xels Seuwyobs
metaboluri darRvevebis gaumjobesebasa da wonis klebas. MMantzoros C.da
Tanaavt. mier Catarebuli kvlevis Tanaxmadac naxSirwylebis SezRudvas
sakveb racionSi da wonis klebas sakmaod mniSvnelovani efeqti aqvs
trigliceridebisa da leptinis daqveiTebis mxriv [237]. aseve
trigliceridebis damaqveiTebeli preparatebic aumjobeseben leptinis
transports hipoTalamusamde.
4.5. leptini da Zvlis mineraluri simkvrive
Cvens kvlevaSi gamovlinda leptinis uaryofiTi korelacia Zvlis
mineralur simkvrivesTan.aRniSnulis Tanaxmad leptinis donis gazrda
dakavSirebuli iyo Zvlis mineraluri simkvrivis daqveiTebasTan. vinaidan
leptinis gazrdili done dadebiTad korelirebs wonasa da smi-sTan,
aRniSnuli Sedegi ewinaaRmdegeba ramdenime wlis win farTod gavrcelebul
mosazrebas imis Taobaze, rom zedmeti wona icavs Zvlovan qsovils
gamofitvisgan.
dReisaTvis monacemebi leptinisa da Zvlis mineraluri simkvrivis kavSirze
gansxvavebulia.Yamauchi et al.mier 2001 wels Catarebuli kvlevidan
gamovlinda, rom leptini dadebiTad korelirebda Zvlis mineralur
simkvrivesTan. regresiuli analizis meTodiT korelacia kvlav
mniSvnelovani darCa, rogorc mTliani sxeulis, ise barZayis yelis Zms-sTan,
mas Semdeg rac moxda sxeulis cximovani cvlisa da asakis gaTvaliswineba
statistikuri damuSavebis dros [238]. Cveni kvlevis Sedegebi msgavsia Thomas
et al –is mier 2001 wels Catarebuli kvlevisa, Tumca aRniSnuli avtoris
74
Tanaxmad leptini dadebiTad korelirebda Zms-sTan mxolod qalebSi da ara
mamakacebSi [239]. Sato et al-is mier Catarebul kvlevaSi ki leptini dadebiTad
korelirebda Zms-sTan mamakacebSic, Tumca wonis CarTvis Semdeg korelacia
daikarga.aRniSnul kvlevebSi monawileobdnen pacientebi sxeulis
normaluri masiT,romelTac ar aReniSneboda leptinis mimarT rezistentoba.
savaraudod, swored es iyo mizezi imisa, romleptini asocirdeboda Zvlis
mineraluri simkvrivis gazrdasTan [240].
Cveni kvlevis SemTxvevaSi, pacientebis umetesobas aReniSneboda leptinis
mimarT rezistentoba.leptinis mimarT rezistentobis gamo SesaZloa
iTrguneba leptinis dadebiTi efeqti Zvalze. aqedan gamomdinare, leptini
SesaZloa astimulirebs Zvlis formirebas mxolod axalgazrda asakSi da
normaluri smi-is dros, rodesac misi done normis farglebSia. Cveni
kvlevis Tanaxmad leptinis done dadebiTad korelirebda Zvlis mineralur
simkvrivesTan axalgazrda da normaluri wonis mqone pirebSi.
msgavsi Sedegebi gamovlinda ramdenime kvlevis mixedviTac, sadac Warbi
wona asocirdeboda Zvlis mineraluri simkvrivis daqveiTebasa da
motexilobis gazrdil riskTan.
savaraudod aRniSnulis mizezi aris leptinis Zvalze moqmedebis
specifiuroba, rac iTvaliswinebs sqess, Zvlis Semadgenlobis Taviseburebas
da ConCxis gansazRvrul nawilebze mis sxvadasxva moqmedebas.
mravalricxovani kvlevebis Sedegad dadginda leptinis rogorc uaryofiTi,
ise dadebiTi zegavlena Zvalze. Cveni kvleva erT-erTi maTgania, sadac
gamovlinda leptinis gazrdili donis uaryofiTi gavlena Zvlis mineralur
simkvriveze.vinaidan Sedegebi arasrulfasovani da sadavoa, meti
farTomasStaburi kvlevaa saWiro imisTvis, rom naTlad ganisazRvros
leptinis efeqti Zvlovan qsovilze.
4.6. kvebis sxvadasxva stilisgavlena leptinze
75
leptinis donis daqveiTeba gamoiwvia, rogorc cximiT Raribma, ise
naxSirwylebiT Raribma kvebam, Tumca am ukanasknelis dros leptinis
daqveiTeba ufro mniSvnelovani iyo.
aRniSnuli Sedegis gaTvaliswinebiT, SesaZlebelia eqimebisTvis praqtikuli
rekomendaciebis micema. kerZod, Tu romeli kvebis reJimia ufro efeqturi
rogorc trigliceridebis, ise leptinis donis daqveiTebis TvalsazrisiT.
savaraudoa, rom wonis daqveiTebam Tavdapirvelad gamoiwvia
trigliceridebis daqveiTeba. aRniSnulis Sedegad sisxlidan tvinamde
leptinis gadaadgilebis gaumjobesda da Sesabamisad leptinma Tavisuflad
ganaxorciela wonis klebis efeqti, madis daqveiTebisa da energiis
danaxarjis gazrdis Sedegad.
Cvens kvlevaSi kvebis orive stilma mniSvnelovani SedegebiaCvena, rogorc
wonis klebis, ise trigliceridebisa da leptinis donis daqveiTebis
TvalsazrisiT.
Tumca, kvlevis Sedegad dafiqsirda, rom naxSirwylebis SezRudva
gacilebiT ukeT moqmedebs wonis klebaze, trigliceridebis donis
daqveiTebasa da leptinis koncentraciis Semcirebaze, vidre cximebiT
Raribi dieta.
sxvadasxva kvlevebis Sedegebi cxadyofen, rom dietas aqvs mniSvnelovani
gavlena leptinis koncentraciaze. Kratz M. da Tanaavt, iseve rogorc
Pelleymounter MA.da Tanaavt. Tanaxmad mniSvneloba aqvs ara martocximebis
raodenobas, aramed cximovani mJavebis tipsac. energiis raodenobac aseve
mniSvnelovnad asocirdeba hormonTan [241, 47]. Martin LJ da Tanaavt. Tanaxmad
naxSirwylebis miReba aseve mniSvnelovnad aregulirebs leptinis dones,
rac SesaZloa insulinis sekreciis cvlilebis mizezi iyos.dadasturebulia,
rom naxSirwylebiT mdidari sakvebi ufro metad zrdis postprandialuri
leptinis koncentracias, vidre cximiani sakvebi [242]. vinaidan simsuqne
mniSvnelovani etiologiuri faqtoria metaboluri sindromis, Saqriani
diabetisa da gul-sisxlZarRvTa daavadebebisTvis, kvebis Taviseburebebs
76
sakmaod didi mniSvneloba aqvT simsuqnisa da aRniSnuli qronikuli
daavadebebis marTvaSi. Jensen MK. da Tanaavt. mier 2006 wels
CatarebulikvlevebiTaa dadasturebuli, rom ujredisiT mdidari sakvebis
didi odenobiT miReba zrdis leptinis mimarT mgrZnobelobas da
akontrolebs leptinis sekrecias. Sesabamisad SesaZlebelia, rom leptinis
pasuxi gansxvavebuli iyos sxvadasxva tipis naxSirwylebis dros [243].
sqesi da sxeulis cximovani qsovili ori mniSvnelovani faqtoria, rac
leptinis koncentraciazemoqmedebs. Cveni kvlevis SemTxvevaSi mdedrobiTi
sqesi da simsuqne aris zustad is ori faqtori rac asocirdeba
hiperleptinemiasTan.
Cvens kvlevaSi ar momxdara cilebis zegavlenis gamokvleva leptinis
koncentraciaze.Weigle DS mier mowodebuli publikaciis Tanaxmad, cilovani
kveba zrdis maZRrobis grZnobas da leptinis koncentracias centralur
nervul sistemaSi, iseve rogorc leptinis mimarT mgrZnobelobas, rac xels
uwyobs wonis SenarCunebas da klebasac ki [244].vinaidan cilovan kvebas
xangrZlivi periodiT SesaZloa hqondes janmrTelobaze sxvadasxva
uaryofiTi zegavlena, Cven aRniSnuli jgufis gamokvleva am etapze ar
CavTvaleT mizanSewonilad.
Semdgomi kvlevebia saWiro imisTvis, rom dadgindes Tu trigliceridebis
maregulirebeli romeli preparati, kvebis stili annutrientebis kombinacia
ukeT moqmedebs metaboluri darRvevebis gaumjobesebaze Warbi wonisa da
simsuqnis mqone pacientebSi.Tumca kidev erTxelaa aRsaniSnavi, rom
leptinis koncentracia mniSvnelovnad damokidebulia kvebasa da dietaze.
daskvnebi
77
1. Sratis leptini dadebiTad korelirebs kardiometabolur risk-
faqtorebTan, kerZod, welis garSemowerilobasTan, sistolur da
diastolur arteriul wnevasTan, trigliceridebis donesTan;
2. Sratis leptini dadebiTad korelirebs cximovani qsovilis
raodenobasTan da misi gadanawilebis androidul tipTan, rac
SesaZloa metyvelebdes leptinis kavSirze dislipidemiasTan da
Sesabamisad gul-sisxlZarRvTa daavadebis gazrdil riskTan;
3. hiperleptinemia SesaZloa iyos normaluri wonis populaciaSi kardio-
vaskuluri riskis prediqtori;
4. dafiqsirda Sratis leptinis uaryofiTi korelaciuri kavSiri Zvlis
mineralur simkvrivesTan;
5. kvebis racionSi naxSirwylebiT mdidari sakvebis SezRudvis sapasuxod
gemovlinda leptinis donis ufro mkveTri daqveiTeba, cximebiT Rarib
dietasTan SedarebiT.
praqtikuli rekomendaciebi:
78
1. Warbi wonisa da simsuqnis mqone pacientebSi leptinis gamokvleva
gvexmareba metaboluri darRvevebis adreul diagnostikasa da
profilaqtikuri RonisZiebebis droul gatarebaSi; es xels Seuwyobs
simsuqnesa da metabolur sindromTan dakavSirebuli garTulebebis
Semcirebas;
2. leptinis uaryofiTi kavSiri Zvlis mineralur simkvrivesTan,
SesaZloa iyos momavalSi motexilobebis prediqtori;
3. leptinis daqveiTebisTvis mizanSewonilia naxSirwylebis SezRudva
kvebis racionSi. wonis klebis Sedegad qveiTdeba trigliceridebis
done da leptinis koncentraciac, rac kidev ufro metad uwyobs xels
wonis klebas da kardiometaboluri darRvevebis gamosworebas an maTi
ganviTarebis Tavidan acilebas.
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