Martha 1. Targeting adipose tissue with dietary oils - new findings on fatty acids and chronic disease 2 Martha A Belury, Ph.D., R.D. Carol S. Kennedy.

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

[email protected]

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

oss

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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