OBESITY

1. OBESITY

2. What is obesity? a disorder of body weight regulatory systems characterized by an accumulation of excess body fat Currently, obesity is epidemic generally as: • abundance of food • reduced activity

3. Whyobesityis major problem ? • The risk of associateddiseaseshas increased: - DM - hypertension - cardiovascular diseases • Childhood obesity ( 3 fold increase in prevalence over the last decades )

4. Assessment of obesity • Aim is to measure amount of body fat • Direct measurement is difficult • Indirect measurement: body Mass Index (BMI): correlate with amount of body fat in most individuals exceptions: athletes : large amounts of lean muscle mass Weight in kg BMI = ______________ 2 (height in meters) 19.5 – 25 : healthy 25 – 29.9 : overweight 30 or more : obese

5. Anatomic differences in fat deposition Anatomic distribution of body fat has a major influence on associated health risks • Android, apple-shaped or upper body obesity excess fat in central abdominal area waist to hip > 1 in men 0.8 in women common in males associated with a greater risk of hypertension, insulin resistance, DM, dyslipidemia & coronary heart diseases • Gynoid, pear-shaped or lower body obesity excess fat in lower extremities around the hips or gluteal region waist to hip < 1 in men 0.8 in women relatively benign healthwise common in females

7. Biochemical differences in regional fat depots • Abdominal fat cells: much larger than lower body fat cells higher rate of fat turnover hormonally more responsive more in men: lose weight readily than women • Substances released from abdominal fat (as free fatty acids) are absorbed via portal vein with direct access to the liver • Free fatty acids from abdominal fat & taken up by the liver may lead to: - insulin resistance - increased synthesis of triacylglycerol , released from liver as VLDL --- LDL • Fatty acids from gluteal fat enter the general circulation -with no preferential action on liver metabolism

8. Number of fat cells Obesity = increase in size + increase of number of adipocytes

9. Body weight regulation Each individual has a biologically predetermined natural set pointfor body weight • around which body weight drifts (within 10%) • reflects a balance between factors that influence food intake & energy expenditure • The body attempts to: - gain weight when the body weight falls below the set point - lose weight when the body weight is higher than the set point So, body weight is stable as long as the behavioural & environmental factors that influence energy balance are constant

11. Genetic contributions to obesity • Genetic mechanisms play a major role in determining body weight • Obesity is observed clustered in families • If both parents are obese : 70-80% chance of the children being obese • If both parents are lean : 9% chance • Inheritance of obesity: - complex polygenic interaction between multiple genes & environment - NOT simple Mendelian genetics (not single gene disorder) • Identical twins: have a very similar BMI (more similar than nonidenticaldizygotic twins)

12. Environmental & behavioural contributions to obesity • explain the epidemic of obesity over the last decade (as genetic factor are stable on this short time scale) • Environmental factors: - ready availability of palatable energy-dense foods - sedentary life-style : TV watching for a long time wide dependency on cars computer using energy-sparing devices at home & at work decrease physical activity • Eating behavioural factors: snacking portion size individual`s unique food preferences number of people with whom one eats

13. Molecules that influence obesity • afferent signals reach the hypothalamus: - neural signals - circulating hormones - metabolites • Hypothalamus releases efferent signals (peptides) that influence appetite & energy expenditure

14. Adipose tissue (adipocytes) LEPTINRESISTINADIPONECTIN Stomach GHRELIN

15. Hormones of adipose tissue • Fat cells (adipocytes): store fats function as endocrine cells • release many regulatory molecules as leptin, adiponectin & resistin

16. Leptin • is the hormone product of the gene ob • secreted by fat cells (adipocytes) • produced proportionally to adipose mass • Acts on the hypothalamus of the brain to regulate the amount of body fat through the control of appetite & energy expenditure • Leptin secretion is : suppressedby starvation enhanced by well-fed state

17. Leptin(cont.)

18. Leptin(cont.) • In mice, daily injection of leptin causes non-obese & overweight mice to lose weight • In humans, leptin increases metabolic rate & decreases appetite • In obese persons, plasma leptinis normal for their fat mass indicating the resistance to leptin • Hypothamic receptors for leptin is produced by db gene • Mutations of db geneproduces leptin resistance (in rodents) BUT not in most human obesity

19. Ghrelin • A peptide secreted primarily in the stomach • Peptide-stimulating hormone • In rodents, injection of ghrelin: increases food intake decreases energy expenditure decreases fat catabolism

20. Metabolic changes observed in obesity • Metabolic abnormalities of obesity reflect molecular signals originating from the increased mass of fat cells

21. Metabolic effects of obesity:Metabolic Syndrome (insulin resistance syndrome or syndrome X) • Insulin resistance • Hyperinsulinemia • Glucose intolerance (& DM) • Dyslipidemia (low HDL & elevated VLDL) • Hypertension WITH SIGNIFICANTLY INCREASED RISK OF DEVELOPING DM & CARDIOVASCULAR DISORDERS men with the syndrome are 3 – 4 times more likely to die from cardiovascular disease

22. Metabolic effects of obesity:DysLipidemia • insulin resistance in adipose tissues causes increased activity of hormone-sensitive lipase resulting in increased free fatty acids released in blood • In the liver, free fatty acids are converted to cholesterol & triacylglycerol • Excess cholesterol & triacylglycerol are released as VLDL resulting in increased serum triacylglycerol & hyperchlosterolemia with increased risk of CHD

24. Obesity & Health 1- Obesity is associated with increased risk of death 2- Obesity is a risk factor for many chronic diseases: type 2 DM hyperchlosterolemia high plasma level of triacylglycerol hypertension coronary heart diseases some cancers gallstones arthritis gout

26. Weight Reduction GOALS of weight management in obese patients: • To induce negative energy balance to reduce body weight decrease caloric intake and/or increase energy expenditure • To maintain a lower body weight over a longer term

27. Weight reduction:1- Physical activity • increases cardiopulmonary fitness & reduces risk of cardiovascular diseases(independent on weight loss) • Combination of caloric restriction & exercise with behavioural treatment may be expected to reduce 5 – 10 % of weight over a period of 4-6 months • Essential for maintaining weight reduction

28. Weight reduction:1- Caloric restriction • 1 pound of adipose tissue (~ 0.5 kg) corresponds to about 3500 Kcal • Ineffective for a long term for many obese individuals • More than 90% regain the lost weight after suspension of dieting • Weight losses of 10% of body weight over a 6-month period often reduces blood pressure reduces lipid levels enhance control of type 2 DM

29. Weight reduction:1- Pharmacological treatment • For BMI 30 or more: 1- sibutramine: appetite suppressant inhibits serotonin & norepinephrine reuptake 2- orlistat: lipase inhibitor that inhibits gastric & pancreatic lipases

30. Weight reduction:1- Surgical treatment • To reduce food consumption • For severely obese patients