Getting Ahead of the Curve in the Trouble with Fat

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1 Getting Ahead of the Curve in the Trouble with Fat Zhaoping Li, M.D., Ph.D. Professor of Medicine David Geffen School of Medicine, UCLA VA Greater Los Angeles Health Care System

2 Obesity Pandemic Predicted Finkelstein et al American J of Preventive Medicine, May % of Americans Obese by % more than 100 pounds overweight $550 billion of obesity-related health care costs 2

3 Obesity Pandemic Predicted 17 percent of children and adolescents are obese children 3

4 Epicenter of the Epidemic China India

5 NHLBI Definitions BMI 25 kg/m2 = Overweight BMI 30 kg/m2 = Obesity

6 Body Mass Index

7 Body Mass Index BMI: 30.2 BMI: 29.1

8

9 Size 12 Size 12 Size 12 Size 12 Size 12 Size 12 Size 12 Size 12

10 Intra-Abdominal fat Spare Tire

11 Umbilical Images from Subjects with BMI 24 kg/m 2

12 Visceral vs. Subcutaneous Adipose Tissue Visceral SQ

13 Visceral vs. Subcutaneous Adipose Tissue Visceral (abdominal, omental) fat correlates better with the comorbidities of obesity including insulin resistance and diabetes Visceral fat is more metabolically active Visceral SQ

14 Waist Circumference Excess abdominal fat independent risk factor for co-morbidities LOW RISK: Men: < 40 Women: < 35 HIGH RISK: Men: > 40 Women: >35

15 Same Waist Circumference IAAT= 0.53 l IAAT= 1.31 l IAAT= 4.2 l IAAT= 1.11 l IAAT= 1.15 l IAAT= 4.26 l

16 Unhealthy at Size 2?

17 Distribution of Body-Mass Index and Percentage Body Fat for Females according to Race/Ethnicity 40.0 r 2 asians = Percent Fat r 2 whites = BMI Asians Whites Asians Whites

18 Measurements of Body Fat Body Fat Mapping Total adipose tissue Regional adipose tissue: Subcutaneous Peripheral Abdominal Internal Peripheral Abdominal (Visceral) Inter-muscular (EMCL) Intramyocellular (IMCL) Pericardial Hepatic (IHCL) Pancreatic Popliteal

19 Adiposopathy Sick Fat Pathologic adipose tissue anatomic/functional disturbances leading to metabolic diseases Bays et al Future Cardiol 2005

20 Adiposopathy Sick Fat Exacerbated by limited or impaired adipogenesis in peripheral, subcutaneous adipose tissue resulting in fat deposition in other depots and in other body organs Bays et al Future Cardiol 2005

21 illustration by Craig Skaggs

22 Adipokines

23 Receptors Expressed in Adipose Tissue

24

25 Integration between Macrophages & Adipocytes

26 Adipose Tissue Response to Excess of Calorie

27 Obese Rhesus Monkeys Treated with Adipotide Barnhart K F et al. Sci Transl Med 2011; Nov 9;3(108): 108ra112

28

29 Body Weight, Body Fat, and Lean Body Mass During 8 Weeks of Overeating Bray, G. A. et al. JAMA 2012;307:47-55

30 Prevention of weight regain Percentage weight regain after body weight loss in the additional-protein group (n=73) vs the control group (n=75). * P<0.01,

31 Maintenance of Lean body mass with higher protein intake Time course changes for the ratio of loss of body fat compared with loss of lean body mass (fat/lean) during weight loss for adult women consuming diets with a carbohydrate (CHO)/protein ratio of 3.5 (CHO Group) or 1.4 (Protein Group). Layman DK et al. J. Nutr. 133: , 2003

32 Maintenance of Lean body mass with higher protein intake fat as % of loss: CHO = 68% PRO = 80% Time course changes for the ratio of loss of body fat compared with loss of lean body mass (fat/lean) during weight loss for adult women consuming diets with a carbohydrate (CHO)/protein ratio of 3.5 (CHO Group) or 1.4 (Protein Group). Layman DK et al. J. Nutr. 133: , 2003

33 Maintenance of Lean Body Mass with Higher Protein Intake Treyzon et al Nutr J Aug 27;7:23

34 Increased Satiety with Higher Protein Intake Perceived satiety for subjects consuming high-protein (HPLF, n = 9) or highcarbohydrate (HCLF, n = 7) low-fat, energy-restricted diets for 6 wk using a 7-point Likert scale.

35 Batterham et al. Cell Metab

36 Fructose is Not Glucose Fructose does not suppress ghrelin Acute fructose does not stimulate insulin nor leptin Hepatic fructose metabolism is different Chronic fructose exposure promotes the metabolic syndrome Eliot et al. Am J Clin Nutr Nutr, 2002 Bray et al. Am J Clin Nutr Nutr, 2004 Teff et al. J Clin Endocrinol Metab Metab, 2004 Gaby, Alt Med Rev, 2005 Wei et al. J Nutr Biochem Biochem, 2006, Johnson et al. Am J Clin Nutr 2007 Rutledge and Adeli Adeli, Nutr Rev, 2007 Brown et al. Int. J.Obes Obes, 2008

37 Fructose Metabolism in Liver Elliott, S. S et al. Am J Clin Nutr 2002;76:

38 Fructose Increases de novo Lipogenesis Hellerstein et al. Ann Rev Nutr 16:523, 1996

39

40

41

42 Sources of n-3 Fatty Acids Fish Krill Algae Plants

43 Are All n-3 Fatty Acid Supplements Equal? ALA EPA DHA

44 Protein Based Meal Replacement

45 The Partial MR Plan For Two Meals/d Baseline Calorie Intake Breakfast Lunch Dinner Snacks Calorie Intake On MR Plan Breakfast Lunch L-SF Dinner Snacks B-SF MR MR Calories saved by MR 2200 Cal/d 1600 Cal/d Ashley, et al Obesity Res. 2001;9:312S-3120S

46 Caffeine EGCG Tea (epigallocatechin gallate) Gallic Acid

47 Green Tea Extract &Thermogenesis p<0.01 Energy Expenditure (kj) Diurnal Nocturnal 0 Placebo Caffeine Green Tea Extract Dulloo AJCN 1999

48 Human Microbiome and Obesity Human body as mixture of human + microbial cells and genomes Microbiome = microbiota s gene content

49 Nature January 22; 457(7228):

50 Mechanisms Linking the Microbiota to Obesity Gut Microbes and Host Metabolism energy extraction from the diet, with variable efficiency affect host adiposity by influencing metabolism throughout the body Gut Microbes, Inflammation, and Insulin Resistance Gut Microbes and Endocrine Cells

51 Etiology of Obesity: Numerous Complex, Interrelated Factors Genetic Neurologic and Physiologic Biochemical Environmental Cultural and Psychosocial Adapted from Weighing the Options; 1995: Clinical guidelines. National Heart, Lung, and Blood Institute Web site. Available at: Accessed July 31, 1998.

52 Visfatin Hypothalmus Brain Hind Brain Ghrelin Resistin Adiponectin Stomach Leptin Insulin Amylin PYY3-36 GLP-1 GI Tract Visceral Fat Cell Glucago n GIP Oxyntomodulin Glicentin CCK Islet Adapted from Badman MK and Flier JS; Science 2006: 307,

53 Visfatin Hypothalmus Brain Hind Brain Ghrelin Resistin Adiponectin Stomach Leptin Insulin Amylin PYY3-36 GLP-1 GI Tract Visceral Fat Cell Glucago n GIP Oxyntomodulin Glicentin CCK Islet Adapted from Badman MK and Flier JS; Science 2006: 307,

54 H Bays. J Am Coll Cardiol Jun 21;57(25):

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