carel le roux - irspen
TRANSCRIPT
How the gut talks to the brain?
Carel le Roux
Diabetes Complications Research Centre
University College Dublin
Imperial College London
University of Gothenburg
Conflict of interest
NovoNordisk,
Johnson & Johnson,
ONO pharmaceuticals,
Covidien,
Fractyl,
GI Dynamics,
Roche,
AstraZeneca
Afferent factors in appetite regulation
LeptinGO
Insulin
PYY
GLP-1
OXM
Ghrelin
Vagus
CCK
Food Intake
Energy Expenditure
0
10
20
30
40
250 500 1000 1000 2000 3000
Lean
Obese
PYY
(pmol/L)
Test meal (kcal)
500 mL 900 mL
Calorie Intake vs PYY dose response
*
*
*
*
* *
le Roux et al Endocrinology 2006
PYY3-36 dose response in humans
Calorie intake Satiety
* P<0.05
20
10
5
0
Doses pmol/kg/min
Saline
mm
fro
m b
aselin
e
15
0.2 0.4 0.5 0.6 0.7 0.8
* * * *15
-15
-30
Doses pmol/kg/min
Saline
Calo
ries (
% o
f salin
e)
0
0.2 0.4 0.5 0.6 0.7 0.8
* *
le Roux et al. Endocrinology. 2006*P ≤.05 vs. saline
Effect of PYY3-36 on food intake
Obese Lean
4000
3000
2000
1000
0Saline PYY
24
-Hr
Calo
ric I
nta
ke (
kcal)
P=0.02
0
4000
3000
2000
1000
Saline PYY
24
-Hr
Calo
ric I
nta
ke (
kcal) P=0.001
Batterham, le Roux et al N Engl J Med 2003
Changes in appetite
Batterham, le Roux et al. N Engl J Med. 2003
10
-10
-20
Minutes
0
Ch
an
ge f
rom
baselin
e (
mm
)
0
30 60 90 120 150 180
20
30
210
Infusion
Peptide YY3-36
Saline
Obese Group
Lifestyle / Meds+1.6%
Banding-13%
Bypass-25%
Weight loss 42
40
36
32
28
24
0 1 2 3 4 6 8 10Years of follow-up
BM
I
kg
/m
2
Long term weight loss maintenance
Sjöström, L. et al. N Engl J Med 2004
Visual analogue scores
How full
0 30 60 90 120 150 1800
25
50
75
100
VAS - How full are you?
Time from end of standard meal (min)
How hungry
0 30 60 90 120 150 1800
25
50
75
100Pre-op
1 month
3 months
6 months
VAS - How hungry are you?
Time from end of standard meal (min)
le Roux, Borg et al 2006 Brit J Surg
PYY response after bariatric surgery
0
10
20
30
40
50
-30 0 15 30 60 90 120 150 180
Lean
Obese
RYGB
Lap Band
Time point (min)
PYY
pmol/L
MEAL
le Roux et al Ann Surg 2006
Blocking gut hormones with octreotide
Gastric banding Gastric bypass
1000
800
600
400
200
0Saline Octreotide
Kcal
1000
800
600
400
200
0Saline Octreotide
Kcal
*
le Roux et al. Ann Surg. 2007*P <0.05
preoperative
Bueter M, le Roux CW & Ashrafian H, unpublished
Clinic – Anecdotal Dietary Change
postoperative
“I Don’t Enjoy Burgers Anymore” Syndrome
Paradoxical – as dietary weight loss increases preference for fatty food and sugars
• High Fat (Flavoured)
• Low Fat (Flavoured)
• Standard High Fat (Control)
le Roux, Spector, Lutz et al Am J Physiol Regul Integr Comp Physiol 2011
Assessment of food preference
Assessment of food preference
le Roux, Spector, Lutz et al Am J Physiol Regul Integr Comp Physiol 2011
Appetative behaviour after RYGB
PRE
POSTPRE
POST
LAS
T C
OM
PLE
TED
RA
TIO
(CLI
CK
S)
0
300
600
900
1200
1500
1800
2100
2400
2700
BREAKPOINT
RYGB CONTROLS
*
Miras, Spector, le Roux et al.
Am J Clin Nutr 2012
Acknowledgements
Science Foundation Ireland, WellcomeTrust, Moulton Foundation, NIHR
University College Dublin,
Catherine Godson, Donal O’Shea,
Neil Docherty, Karl Neff, Sabrina Jackson, Sinead McDermott, Stephen Kearney, Jessie Elliott
Trinity College Dublin
John Reynolds
University of Gothenburg
Torsten Olbers, Lars Fandriks, Almantas Maleckas, Lena Carlsson, Per-Arne Svensson
Imperial College London
Steve Bloom, Mohammad Ghatei, Alex Miras, Andrew Frankel, Fred Tam, Julian Teare
King’s College London
Francesco Rubino, Stephanie Amiel, Simon Aylwin, Ameet Patel, Cynthia Borg
University of Zurich
Thomas Lutz, Marco Bueter
Musgrove Hospital, Taunton
Richard Welbourn, Rob Andrews, Dimitri Pournaras, Alan Osborn
Florida State University
Prof Alan Spector
Oswaldo Hospital, Soa Paulo
Ricardo Cohen
Catholic University of Chile
Camilo Boza
Saudi Arabia
Al-Qahtani, Ghalia Abdeen