کنترل وزن

1. بنام خداوند جان و خرد کنترل وزن دکتر منصور سیاوش

3. مفاهیم اولیهّ • مقدمه • اهداف بحث • چاقی یا لاغری از نظر اجتماعی و تاریخی

4. چاقی یا لاغری از نظر اجتماعی و تاریخی

5. مفاهیم اولیهّ • وزن بدن ناشی از چیست؟ در یک فرد 70 کیلوئی: kg 42 آب kg 12 پروتئین kg 12 چربی kg 0.5 گلیکوژن kg 3.5 وزن غیر انرژی زا

6. تغییرات وزن در طول زندگی چگونه است؟

7. تغییرات BMI از کودکی تا بلوغ

8. تغییرات وزن در بالغین با افزایش سن

9. پاتوفیزیولوژی تغییرات وزن • ∆ E = Q – W • If ∆ E = 0 →→ Energy intake = Energy expenditure

12. سیستم های کنترل کننده وزن بدن کدامند؟

13. چه عواملی بر تعیین وزن بدن تاًثیر گذارند؟ • وزن پدیده ای مولتی فاکتوریال و حاصل تداخل عوامل زیر است • وراثت • میزان مصرف مواد غذائی(کسب انرژی) • میزان فعالیت فیزیکی(برون ده انرژی)

14. وراثت یا محیط ؟

15. وراثت • وراثت مهمترین عامل تعیین کننده وزن در زمان طولانی است. • هنوز ژن عامل چاقی شایع در انسان شناخته نشده است. • برخی ژنها مثل ژن لپتین، گیرنده لپتین،MCR4 شناخته شده است.

16. تمایل ژنها به سمت ایجاد چاقی است یا لاغری؟

19. مصرف مواد غذائی • عوامل محیطی-اجتماعی • هورمونهای دستگاه گوارش • هورمونهای پانکرآس • عوامل مرکزی

20. Environment factors suggested to promote overeating • High Fat/Energy Dense Foods • High Glycemic Index of Foods • Soft Drinks • Sugar • Fast foods • Portion Size • Snack foods • Low calcium • Accessibility of Food • Low Cost of Food • Taste of Food • Variety مصرف مواد غذائی

21. High Fat/Energy Dense Foods High Glycemic Index Food

22. GASTROINTESTINAL PEPTIDES REGULATING FOOD INTAKE Peptide  Stimulus Site of Production Site of Action  Effect on food intake CCK  protein and fat  small intestinebrain vagal afferents  decrease GLP-1 nutrients gut hormonesgut neural signals ileum/colon  gastric emptyingbrain decrease Ghrelin fasting  stomach  brain  increase Apo A-IV fat absorption  intestine/liver  brain  decrease Enterostatin fat  Stomach intestine  vagal afferents  decrease GRP/ Bombesin gastric mucosa  food ingestion  vagal afferents ,brain decrease

23. Gastrointestinal signals regulate food intake. • The majority of signals from the GI tract regulate the size of individual meals.Mechanoreceptors quantitating stretch of the stomach, and chemoreceptors activated by nutrients in the GI tract, transmit information via vagal and sympathetic afferents to the hindbrain nuclei. This information is then transmitted to the hypothalamus and other forebrain structures for integration with additional signals regulating food intake. Vagal afferents from the liver signal the presence of specific nutrients. Glucose and ketones act as signals to the CNS directly on responsive neurons in the hypothalamus. Gastrointestinal hormones such as CCK bind receptors in the liver to activate vagal afferents, or access the CNS via the circulation.Other hormones such as GLP-1 inhibit feeding by slowing gastric emptying.

24. PANCREATIC HORMONES REGULATING FOOD INTAKE Peptide  Stimulus SiteofProduction Site of Action  Effect on food intake Insulin  carbohydrate  b-cell  brain  decrease Amylin  carbohydrate  b-cell  brain  decrease Glucagon  cephalic response  a-cell  liver/vagalafferents  decrease

27. Environmental factors suggested to reduce physical activity? • Reduced need for physical labor in most jobs • Elevators ,Remote controls, Telephone • No required physical activity in schools • Reductions in physical activity required for daily living • Competition from attractive sedentary activities: • television, video/DVD, video/computer games, internet میزان فعالیت فیزیکی

29. سیستم های کنترل کننده وزن بدن کدامند؟

30. کنترل وزن چگونه انجام میشود؟ • سیستم گیرنده وضعیت فعلی نسج چربی را می سنجد. • وضعیت فعلی به اطلاع مرکز کنترل وزن میرسد. • مرکز کنترل وزن اطلاعات دریافتی را با Set point مقایسه میکند. • مرکز کنترل وزن دستورات اصلاحی را در جهت رسیدن وزن به Set point صادر میکند. • مراکز عمل کننده با تغییر در Intake وExpenditure اصلاحات لازم را انجام میدهند.

31. Leptin

32. Leptin • Was discovered in 1994 by Friedman et al . • Is a 16 kd protein produced predominantly in white adipose tissue and, to a lesser extent, in the placenta, skeletal muscle, and stomach fundus in rats. • Has a myriad of functions in carbohydrate, bone, and reproductive metabolism that are still being unraveled . • The major role of leptin in body weight regulation is to signal satiety to the hypothalamus,thus : • Reduces dietary intake and fat storage while modulating energy expenditure and carbohydrate metabolism to prevent further weight gain.

33. Pathway of leptin appetite regulation PC-1 processing enzyme Melanocortin 4 Receptor signal Leptin receptor POMC expression Leptin Alfa MSH AgRP Decreased Appetite

34. Leptin Rx

35. Other biological actions of leptin

36. POMC • Proopiomelanocortin (POMC) and alpha–melanocyte-stimulating hormone (alpha-MSH) both act centrally on the melanocortin receptor 4 (MC4R) to reduce dietary intake . • Genetic defects in POMC production and mutations in the MC4R gene both • have been described as monogenic causes of obesity in humans . • As many as 5% of children who are obese have MC4R or POMC mutations.

37. Prohormone convertase1 • Involved in the conversion of POMC to alpha-MSH. • Patients identified to have mutations of this,although rare, have significant obesity,hypogonadotrophic hypogonadism, and central adrenal insufficiency. • It is one of the few obesity models not associated with insulin resistance.

38. PPAR-gamma • Is a transcription factor that is involved in adipocyte differentiation. • All humans with mutations of the receptor described so far have severe obesity.

39. AgRP • This protein inhibits the binding of melanocyte-stimulating hormone(MSH) to its receptors (melanocortin-1 receptor), thereby reducing melanin pigmentation. • The agouti protein also competes with MSH for a receptor in the hypothalamus (melanocortin-4 receptor) that modulates food intake . • Serum concentrations of the agouti protein are higher in obese than non-obese men .

40. Proposed Mechanism of Action of Resistin in Mice. Whether triglycerides are stored in adipocytes or broken down and released from adipocytes depends on whether there is a positive or negative energy balance, respectively.The adipocyte actively modulates energy balance through the secretion of hormones and other signaling molecules. For example, leptin is secreted by triglyceride-laden adipocytes, travels through the circulation, crosses the blood–brain barrier, and reaches the hypothalamus, where it modulates a host of neuroendocrine and autonomic nervous system activities, resulting in decreased food intake and increased energy expenditure. Resistin, as well as tumor necrosis factor , adiponectin, free fatty acids, and possibly other factors released by adipocytes, act in peripheral tissues to influence sensitivity to insulin and other cellular and metabolic processes involved in the use and partitioning of substrates.

41. Central control of weight

43. Categories of total body energy expenditur

44. Step-by-step conversion of fuel into ATP and then ATP into biological work within the cell. Free fatty acids (FFAs) and glucose are oxidized generating NADH and FADH2 which donate electrons to the electron transport chain. Ubiquinone (Q) shuttles electrons from both complexes I and II to complex III while cytochrome C (C) shuttles electrons from complex III to complex IV. Molecular oxygen (O2) is the terminal electron acceptor. Protons are pumped out by complexes I, III and IV of the electron transport chain creating a proton electrochemical potential gradient (?uH+). Protons may reenter the mitochondrial matrix via the F0F1 ATPase, with energy being used to generate ATP from ADP and Pi. Protons may also reenter via an uncoupling protein (UCP), with energy being released in the form of heat. Proton rentry via ATP synthase depends upon the availability of ADP which is generated in the cytosol from reactions utilizing ATP. • Abbreviations: ANC, adenine nucleotide carrier; CC, carnitine carrier; complex I, NADH-ubiquinone oxidoreductase; complex II, succinate:ubiquinone oxidoreductase; complex III, ubiquinone-cytochrome-c oxidoreductase; complex IV, cytochrome-c oxidase; PiC, phosphate carrier; PyC, pyruvate carrier.

46. Coupling of reactions in energy metabolism and the operation of "futile cycles". Metabolism of fuel generates a stoichiometric amount of NADH and FADH2. Oxidation of NADH and FADH2 results in 10 and 6 protons, respectively, being pumped out of the mitochondrial matrix. Three protons enter via ATP synthase in order to synthesize one molecule of ATP from ADP and Pi. One additional proton enters the matrix as it is co-transported with Pi via the phosphate carrier. ATP is then utilized to perform a fixed amount of work. The major consumers of ATP are shown above. Muscle relaxation, ion leaks, protein degradation and dephosphorylation create the possibility for "futile cycles".

47. Energy Expenditure is Regulated by the Brain • Central and efferent pathways regulating energy expenditure. Diet and cold is sensed by the brain. In the case of diet-induced thermogenesis, a strong case can be made for the role of aMSH neurons in the arcuate nucleus of the hypothalamus which project to neurons in the paraventricular nucleus of the hypothalamus controlling sympathetic outflow, as well as to sympathetic preganglionic neurons located in the intermedial lateral column of the spinal cord. As discussed in the text, MC4Rs are likely to play an important role. These pathways lead to increased activity of sympathetic nerves which release norepinephrine, activating bARs. This has acute and chronic effects on brown adipocytes which promote increased thermogenesis. This figure was adapted from reference

49. وزن متناسب چیست؟

50. برای ارزیابی وزن چه شیوه هائی وجود دارد؟ • Weight • Weight chart • BMI • Anthropometric assessment • MRI/CT • Hydrodensitometry