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 Professor of Nutrition 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 3

Obesity is a condition where there is an excess of adipose tissue § Storage of Oil droplets  Triglycerides 3 fatty acids + glycerol  Energy  Insulation Secretes cytokines & adipokines  Interleukin 6  Leptin & Adiponectin

5 Central Obesity Alzheimers Some Cancers Heart Disease MetS & T2 Diabetes

One third of adults have metabolic syndrome 3 or more: Abdominal obesity Impaired fasting glucose Atherogenic dyslipidemia Elevated blood pressure 6 ATP III Criteria: Grundy et al., Circulation 25: 2735 (2005) Weight loss

Distribution of adipose is a key driver of the metabolic syndrome 7

Outline I. The “Skinny” on Fats II. What’s in the news about fats? III. How Do Fats Work? IV. What do we know? 8

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 9 16:0 Palmitic Acid Shortening, 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 10 18:0 Stearic acid Animal-derived saturated fats

11 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 11 18:1n9 Oleic acid Animal-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 18:2n6 Linoleic acid (octadecadienoic acid) 12

Linoleic acid (18:2n6)  Major PUFA in US diet  Functions Phospholipids: growth of tissues Barrier for epithelial tissues Lipid metabolism  Arachidonic acid & Eicosanoids  Hepatic cholesterol metabolism 13

Sources of linoleic acid 14

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

 -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 16

Alpha-linolenic acid (A-LNA; 18:3n3) Eicosapentaenoic acid (EPA; 20:5n3) Docosahexaenoic acid (DHA; 22:6n3) 17

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. Muscle B. Liver C. Heart D. Adipose E. All of the above 20

What do you know? 2. Adipose tissue functions to: A. Store energy B. Insulate the body C. Alter gene expression D. Alter inflammation E. All of the above 21

Fatty Acids Can Turn on Gene Expression Fatty Acids bind to proteins Transcription Factors  Turn on Gene Expression  Responsive genes that regulate: Fat metabolism Energy metabolism 22 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) 23

II. What’s in the news about Fats? 24

t10c12-CLA c9t11-CLA Linoleic acid (LA 18:2n6) Conjugated linoleic acids (CLA) 25

Conjugated Linoleic Acid (CLA) Oil Fraction of Ruminant Products Dietary supplements 26

CLA Causes Weight Loss in Fat (ob/ob) Mice 27

Very Low Dose* t10c12-CLA Shrinks Adipocytes CON CLA § *0.11wt% of diet, 17 days

CLA Increases Basal Temperature (ob/ob mice) 29

30 Does CLA Burn Fat* in Humans? * ‘Burn’ mean induce thermogenesis

31 Ohio State University Women’s Diabetes Study

32 t10c12-CLA c9t11-CLA Linoleic acid (LA 18:2n6)

N=55 women Postmenopausal Age BMI Diabetes yrs Medication Classes Sulfonylureas13 Biguanides13 Thiazolidinediones5 Incretin Mimetic10  -Glucosid inhibitor1 Combination Therapy22 Ohio State University Women’s Diabetes Study 33

CLA reduces body weight 34

1 lb. adipose = 3500 kcal 35 Does CLA Shrink Adipose?

1. CLA lowers total adipose mass 2. SAF lowers trunk adipose mass 36 Norris et al., lbs -3.7 lbs

SAF Oil increases HDL 37

Cytokines *

SAF oil improves glycemia 39

So far…. In Postmenopausal women with T2 DM: CLA  reduces BMI and adipose mass  no effect on markers of glycemia SAF  reduces trunk adipose mass, HbA1C, glycemia  increases HDL and lean body mass 40

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 Women No. (%)23 (74%)33 (83%)27 (77%) BMI 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 stress Omega 6: Omega 3 ratio Decreased marker of aging (telomere length) 42

What do you know? 3. Safflower Oil is rich in: A. Saturated fat B. Monounsaturated fat C. Omega 6 polyunsaturated fat D. Omega 3 polyunsaturated fat E. CLA 43

What do you know? 4. In Postmenopausal women with T2 DM women, CLA: A. Decreased body weight and adipose mass B. Increased central adipose mass C. Decreased glycemia D. All of the above 44

What do you know? 5. Safflower oil supplementation _____ in postmenopausal women with type 2 diabetes. A. Increased inflammation B. Improved glycemia C. Decreased HDL D. Increased trunk adipose E. None of the above 45

46 What do you know? 6.Fish Oil A. Decreased inflammation B. Caused faster aging in people C. Decreased HDL D. Decreased adipose mass E. None of the above 46

7 th Inning Stretch 47

III. How Do Fats Work on MetS? 48 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) 49 Peroxisome Proliferator-Activated Receptors (PPARs)

PPARs Proteins that interact with Fatty Acids / some drugs Transcription Factors  Turn on Gene Expression  Responsive genes: Fat metabolism Energy metabolism 50 Fatty Acid PPAR

What is in Safflower oil? Linoleic acid (78wt%) Tocopherols 51

52 What is in Fish oil? Long chain PUFAs  EPA (70%)  DPA (5%)  DHA (10%) Many other fatty acids (15%) 52

Fat RE Target Gene Protein = PPAR Nucleus Cytosol 53 Responsive Genes: CHO, lipid, protein metabolism

Choose Your Calories by the Company They Keep 54 Linoleic acid tocopherols flavonoids Long chain omega 3s High quality protein Lean protein Minerals bio-available

IV.What do we know? 55

Construct the conversation: Keep it simple 56

57 1⅔ teaspoon

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What do we know? 1. Kinky fats are good for you. True 1. Adding some fats is a good strategy for healthful eating. True 1. Healthful diets are always low in fat, taste bad, lack satiation and generally are boring. True

Know Your Fats & Talk About Fats 60

n6:n3 Ratio Goal: n6:n3 < 4:1 This means INCREASE Omega 3 This Does not Mean DECREASE Omega 6 61

Take Home Messages Dietary oils still have a protective role in preventing heart disease and MetS in a healthy life style 1. Diet 2. Exercise 3. Sleep 4. De-stress 62

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 63

Take Home Messages Keep a sense of of humor and a sense of humility 64

Shop on the Edge 65

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 66

Quiz, True or False 1. 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 68 Omega 3Omega 6t10c12CLASaturated Inflammation  //  Obesity ()()?  Central Obesity/MetS ?  ?? JKG: Negative Mood  ??? LY: Breast Cancer  ?/ //  RJ/TO: Bone disease  /??   /?

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