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Martha. Targeting adipose tissue with dietary oils - new findings on fatty acids and chronic dis ease. Dietary fats and chronic disease. Martha A Belury, Ph.D., R.D. Carol S. Kennedy Professor of Nutrition Belury.1@osu.edu. Obesity is a BIG issue. Decreases mobility & QOL Social stigma

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Martha


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    1. Martha

    2. Targeting adipose tissue with dietary oils - new findings on fatty acids and chronic disease Dietary fats and chronic disease Martha A Belury, Ph.D., R.D. Carol S. Kennedy Professor of Nutrition Belury.1@osu.edu

    3. Obesity is a BIG issue Decreases mobility & QOL Social stigma Increases risk for metabolic, cardiovascular diseases & some cancers Increases inflammation

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

    5. Inflammation & Chronic Disease Central Obesity Some Cancers MetS & T2 Diabetes Systemic Inflammation Alzheimers Heart Disease

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

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

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

    9. 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 16:0 Palmitic Acid Shortening, saturated tropical “oils”

    10. 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 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 18:1n9 Oleic acid Animal-derived unsaturated fats, ‘Mediterranean’ oil - Olives, avodacos, 11

    12. 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)

    13. 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

    14. Sources of linoleic acid

    15. 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)

    16. 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 a-Linolenic Acid • Neuronal development and conditions • Visual Health • Appetite • Inflammatory-related diseases

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

    18. Long-Chain Omega Three Fatty Acids • EPA (eicosapentaenoic acid) & DHA (docosahexaenoic acid) • May Protect Against Heart Disease, Certain Types of Cancers • Decrease inflammation

    19. Cold Water Fish • Fortified foods • Supplements

    20. What do you know? • Fatty acids are small molecules that are stored in __________ tissue. • Muscle • Liver • Heart • Adipose • All of the above

    21. What do you know? • Adipose tissue functions to: • Store energy • Insulate the body • Alter gene expression • Alter inflammation • All of the above

    22. Fatty Acids Can Turn on Gene Expression • Fatty Acidsbind to proteins • Transcription Factors • Turn onGene Expression • Responsive genes that regulate: • Fat metabolism • Energy metabolism PPAR Fatty Acid

    23. 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)

    24. II. What’s in the news about Fats?

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

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

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

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

    29. CLA Increases Basal Temperature (ob/ob mice)

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

    31. Ohio State University Women’s Diabetes Study

    32. Women’s Diabetes Study t10c12-CLA c9t11-CLA Linoleic acid (LA 18:2n6)

    33. Ohio State University Women’s Diabetes Study Medication Classes Sulfonylureas 13 Biguanides 13 Thiazolidinediones 5 Incretin Mimetic 1 0 a-Glucosid inhibitor 1 Combination Therapy 22 N=55 women Postmenopausal Age 58 + 7 BMI 36.8 + 6 Diabetes - 9.9 yrs

    34. CLA reduces body weight

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

    36. 1. CLA lowers total adipose mass2. SAF lowers trunk adipose mass -3.7 lbs -3.1 lbs Norris et al., 2009

    37. SAF Oil increases HDL

    38. Cytokines *

    39. SAF oil improves glycemia

    40. 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

    41. Ohio State UniversityFish Oil and Stress in Older Adults Kiecolt-GlaserJK et al., Omega-3 fatty acids, oxidative stress, and leukocyte telomere length: A randomized controlled trial. Brain BehavImmun 2012; in press

    42. Ohio State UniversityFish 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)

    43. What do you know? • Safflower Oil is rich in: • Saturated fat • Monounsaturated fat • Omega 6 polyunsaturated fat • Omega 3 polyunsaturated fat • CLA

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

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

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

    47. 7th Inning Stretch

    48. III. How DoFats Work on MetS? Central Obesity Some Cancers MetS & T2 Diabetes Systemic Inflammation Alzheimers Heart Disease

    49. Agents that Mimic Fats to Affect the Metabolic Syndrome PeroxisomeProliferator-Activated Receptors (PPARs) Thiazolidinediones (Avandia, Actos) Fibrates (Clofibrate, Gemfibrozil, Fenofibrate, Tricor)

    50. PPARs • Proteins that interact with Fatty Acids / some drugs • Transcription Factors • Turn onGene Expression • Responsive genes: • Fat metabolism • Energy metabolism PPAR Fatty Acid