Download - Martha
Martha
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Targeting adipose tissue with dietary oils - new findings on fatty acids and chronic disease
Martha A Belury, Ph.D., R.D.Carol S. Kennedy Professor of
Dietary fats and chronic disease
Obesity is a BIG issue
Decreases mobility & QOL Social stigma Increases risk for metabolic,
cardiovascular diseases & some cancers
Increases inflammation
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Obesity is a condition where there is an excess of adipose tissue §
Storage of Oil dropletsTriglycerides
3 fatty acids + glycerol
Energy Insulation
Secretes cytokines & adipokines Interleukin 6Leptin & Adiponectin
Inflammation & Chronic Disease
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SystemicInflammat
ion
Central Obesity
Alzheimers
Some Cancers
Heart Disease
MetS &T2 Diabetes
One third of adults havemetabolic syndrome
3 or more: Abdominal obesity Impaired fasting glucose Atherogenic dyslipidemia Elevated blood pressure
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ATP III Criteria: Grundy et al., Circulation 25: 2735 (2005)Weight l
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Distribution of adipose is a key driver of the metabolic syndrome
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OutlineI. The “Skinny” on FatsII. What’s in the news about
fats?III. How Do Fats Work?IV. What do we know?
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Saturated Fat
H H H H H H H H H H H H H H H O
H-C--C--C--C--C--C--C--C--C--C--C--C--C--C—C--C-OH
H H H H H H H H H H H H H H H
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16:0Palmitic AcidShortening, saturated tropical “oils”
Saturated Fat
H H H H H H H H H H H H H H H H HO
H-C--C--C--C--C--C--C--C--C--C--C--C--C--C--C--C--C-C-OH
H H H H H H H H H H H H H H H H H
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18:0Stearic acidAnimal-derived saturated fats
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Monounsaturated Fat
H H H H H H H H H H H H H H HO
H-C--C--C--C--C--C--C--C--C--C--C--C--C--C--C--C--C-C-OH
H H H H H H H H H H H H H H H H H
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18:1n9Oleic acidAnimal-derived unsaturated fats,‘Mediterranean’ oil - Olives, avodacos,
Polyunsaturated Fat
H H H H H H H H H H H H HO
H-C--C--C--C--C--C--C--C--C--C--C--C--C--C--C--C--C-C-OH
H H H H H H H H H H H H H H H H H
18:2n6Linoleic acid (octadecadienoic acid)
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Linoleic acid (18:2n6)
Major PUFA in US dietFunctions
Phospholipids: growth of tissues
Barrier for epithelial tissues
Lipid metabolismArachidonic acid & EicosanoidsHepatic cholesterol metabolism 13
Sources of linoleic acid
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Linoleic acid lowers cholesterol
“With vegetable oils this decrease [of
cholesterol] is thought to be largely due
largely to a poly-unsaturated fatty acid
known as linoleic acid.”
Page et al., Circulation 15: 97 (1957)15
a-Linolenic Acid
n3 polyunsaturated fats
H H H H H H H H H H H O
H-C--C--C--C--C--C--C--C--C--C--C--C--C--C--C--C—C--C-OH
H H H H H H H H H H H H H H H H H
Neuronal development and conditions
Visual Health Appetite Inflammatory-related diseases
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Alpha-linolenic acid(A-LNA; 18:3n3)
Eicosapentaenoic acid(EPA; 20:5n3)
Docosahexaenoic acid(DHA; 22:6n3)
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Long-Chain Omega Three Fatty Acids• EPA (eicosapentaenoic acid) & DHA (docosahexaenoic acid)
• May Protect Against Heart Disease, Certain Types of Cancers
• Decrease inflammation
• Cold Water Fish• Fortified foods• Supplements
What do you know?
1. Fatty acids are small molecules that are stored in __________ tissue.
A. MuscleB. LiverC. HeartD. AdiposeE. All of the above
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What do you know?
2. Adipose tissue functions to:A. Store energyB. Insulate the bodyC. Alter gene expressionD. Alter inflammationE. All of the above
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Fatty Acids Can Turn on Gene Expression
Fatty Acids bind to proteins
Transcription FactorsTurn on Gene
ExpressionResponsive genes
that regulate: Fat metabolism Energy metabolism
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Fatty Acid
PPAR
Fatty Acids May Alter Inflammation by: Changing adipose size Affecting prostaglandin levels Changing expression of genes that
code for proteins that affect inflammation (IL-6, Adipokines, etc)
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II. What’s in the news about Fats?
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t10c12-CLA
c9t11-CLA
Linoleic acid(LA 18:2n6)
Conjugated linoleic acids (CLA)
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Conjugated Linoleic Acid (CLA)• Oil Fraction of Ruminant Products• Dietary supplements
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CLA Causes Weight Loss in Fat (ob/ob) Mice
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Very Low Dose* t10c12-CLA Shrinks Adipocytes
CON CLA
0.0
500.0
1000.0
1500.0
2000.0
2500.0
3000.0
3500.0
4000.0
CON CLA
groups
Ad
ipo
cyte
Are
a (u
m^
2)
§
*0.11wt% of diet, 17 days
CLA Increases Basal Temperature (ob/ob mice)
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Does CLA Burn Fat* in Humans?
* ‘Burn’ mean induce thermogenesis
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Ohio State University Women’s Diabetes Study
Women’s Diabetes Study
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t10c12-CLA
c9t11-CLA
Linoleic acid(LA 18:2n6)
N=55 women Postmenopausal Age 58 + 7 BMI 36.8 + 6 Diabetes - 9.9 yrs
Medication ClassesSulfonylureas 13Biguanides 13Thiazolidinediones 5Incretin Mimetic 1 0a-Glucosid inhibitor 1Combination Therapy 22
Ohio State University
Women’s Diabetes Study
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CLA reduces body weight
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1 lb. adipose = 3500 kcal35
Does CLA Shrink Adipose?
1. CLA lowers total adipose mass2. SAF lowers trunk adipose mass
36Norris et al., 2009
-3.1 lbs -3.7 lbs
SAF Oil increases HDL
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Cytokines
*
SAF oil improves glycemia
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So far….In Postmenopausal women with
T2 DM: CLA
reduces BMI and adipose massno effect on markers of glycemia
SAF reduces trunk adipose mass, HbA1C,
glycemia increases HDL and lean body mass
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Ohio State University Fish Oil and Stress in Older Adults
Placebo (N=31)
1.25 g/d (N=40)
2.5 g/d (n=35)
Age 51 50 51
Women No. (%) 23 (74%) 33 (83%) 27 (77%)
BMI 31.1 31.7 30.7
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Kiecolt-Glaser JK et al., Omega-3 fatty acids, oxidative stress, and leukocyte telomere length: A randomized controlled trial.Brain Behav Immun 2012; in press
Ohio State University Fish Oil and Stress in Older Adults
Fish Oil Accumulates in plasma as
Increased omega 3 Decreased omega 6
lowers markers of inflammation Decreased oxidative stressOmega 6: Omega 3 ratio Decreased marker of aging (telomere
length)
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What do you know?
3. Safflower Oil is rich in:A. Saturated fatB. Monounsaturated fatC. Omega 6 polyunsaturated fatD. Omega 3 polyunsaturated fatE. CLA
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What do you know?4. In Postmenopausal women
with T2 DM women, CLA:A. Decreased body weight and
adipose massB. Increased central adipose massC. Decreased glycemiaD. All of the above
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What do you know?
5. Safflower oil supplementation _____ in postmenopausal women with type 2 diabetes.A. Increased inflammationB. Improved glycemia C. Decreased HDLD. Increased trunk adiposeE. None of the above
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What do you know?
6. Fish OilA. Decreased inflammationB. Caused faster aging in people C. Decreased HDLD. Decreased adipose massE. None of the above
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7th Inning Stretch
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III. How Do Fats Work on MetS?
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SystemicInflammat
ion
Central Obesity
Alzheimers
Some Cancers
Heart Disease
MetS &T2 Diabetes
Agents that Mimic Fats to Affect the Metabolic Syndrome Thiazolidinediones (Avandia, Actos) Fibrates (Clofibrate, Gemfibrozil,
Fenofibrate, Tricor)
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Peroxisome Proliferator-Activated Receptors (PPARs)
PPARs
Proteins that interact with Fatty Acids / some drugs
Transcription FactorsTurn on Gene
ExpressionResponsive genes:
Fat metabolism Energy metabolism
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Fatty Acid
PPAR
What is in Safflower oil? Linoleic acid (78wt%) Tocopherols
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What is in Fish oil?
Long chain PUFAsEPA (70%)DPA (5%)DHA (10%)
Many other fatty acids (15%)
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Fat
RE Target Gene
Protein = PPAR
Nucleus
Cytosol
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Responsive Genes: CHO, lipid, protein metabolism
Choose Your Calories by the Company They Keep
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Linole
ic acid
toco
phero
ls
flavonoid
s
Long chain omega 3sHigh quality proteinLean proteinMinerals bio-available
IV. What do we know?
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Construct the conversation:Keep it simple
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5757
1⅔ teaspoon
5858
What do we know?
1. Kinky fats are good for you.
True
2. Adding some fats is a good strategy for healthful eating.
True
3. Healthful diets are always low in fat, taste bad, lack satiation and generally are boring.
True
Know Your Fats
&
TalkAbout Fats
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n6:n3 Ratio
Goal: n6:n3 < 4:1This means INCREASE Omega 3This Does not Mean DECREASE Omega
6
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Take Home Messages
Dietary oils still have a protective role in preventing heart disease and MetS in a healthy life style
1. Diet2. Exercise3. Sleep4. De-stress
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Fitting Fats into Your Next Dinner Party Conversation Analogy:
Just like you do not tell a patient to reduce their BMI by becoming taller, …
Construct the conversation by keeping it simple
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Take Home MessagesKeep a sense of of humor and a sense of humility
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Shop on the Edge
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Summary: Proposed Mechanisms CLA and SAF oil have different effects
on body composition and metabolism Fatty acids affect health by changing
gene expression and metabolism As little as 1⅔ teaspoon (8 ml) added
per day
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Quiz, True or False1. Kinky fats are good for you. 2. Adding some oils is a good strategy for
healthful eating.3. Healthful diets are always low in fat,
taste bad, lack satiation and are, generally, quite boring.
Research on Fatty Acids at OSU
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Omega 3
Omega 6
t10c12CLA
Saturated
Inflammation / Obesity () ? Central Obesity/MetS ? ? ?
JKG: Negative Mood ? ? ?
LY: Breast Cancer ?/ / RJ/TO: Bone disease /? ? /?
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