بسم الله الرحمن الرحيم

1. بسم الله الرحمن الرحيم

2. Obesity and Being Overweight By Amr Abdelmonem,MD. Assistant professor of anesthesia ,surgical intensive care and clinical nutrition in faculty of medicine, Cairo university Member of North American Association For The Study Of Obesity Member of the American society of regional anesthesia and pain medicine

3. The O Word:Obesity 1998, world health organization defined overweight and obesity based on Body Mass Index ( BMI Kg / m2) Over weight : 25.0 to 29.9 Class 1 obesity: 30.0 to 34.9 Class 2 obesity: 35.0 to 39.9 Class 3 obesity : 40.0 or greater BMI is not a measure of body composition BMI is an important correlate of impaired HRQL(health related quality of life)

4. National institutes of health of the US have recently recommended weight Management based on Standardized cut- offs for BMI at 25 and 30 Kg/m2 and • On waist circumference ( action levels) • Minimum circumference between lower rib margin and iliac crest • Action level 1 at 94 cm in men and 80 cm in women • Action level 2 at 102 cm in men and 88 cm in women • Greater than action level 1 : individuals are at • increased health risk ,should avoid weight gain • Greater than action level 2 : are at high health risk , • should seek Professional help NICK CIRCUMFERENCE measurement is a simple and time-saving screeningmeasure that can be used to identify overweight and obese patients. Men with NC <37 cm and women with NC <34 cm are not tobe considered overweight

6. The Pathophysiology of Obesity • Cultural Influences on Eating and Activity Patterns • Biologic Factors • Genetic Factors • Effects of Certain Medications • Medical Causes of Obesity

7. Cultural Influences on Eating and Activity Patterns • Both leisure and working time are increasingly sedentary as people move from one seated position to another in their use of the automobile, the television, video games, and the computer

8. The simplistic solution of “’eat less and exercise more’” does it always work?

9. Biological factors Three primary neuroendocrinal components : • Afferent signals (orexigenic and anorexigenic peptides ) • CNS processing unit :VMH-PVN-LHA • Efferent system :complex of effectors • Appetite and its motor component ( medullary NTS) • Autonomic nervous system ,with its 2 pathways: a. sympathetic limb b. parasympathetic limb 3.Three components of total energy expenditure • Resting energy expentiture (50 to 65% ) • Thermal effect of food • Voluntary energy expentiture

10. Afferent signals • Ghrelin hormone • Cholecystokinnin hormone • Bombesin hormone • Leptin hormone • Melanocortins

11. Central processing unit and hypothalamic obesity

12. Efferent system

13. 1.Appetite and its motor components • Nucleus tractus solitarius (NTS) is the central integratorthat control appetite and satiety

14. 2.Autonomic nervous system 1.Sympathetic nervous system (SNS) Activation of the adrenergic beta 3 receptors in adipocytes 2. Parasympathetic nervous system (PNS) Activation of muscarinic M3 receptors ➞acetylcholine ➞ depolarization of beta cell ➞calcium influx ➞ hyperinsulinemia

15. 3.Components of energy expenditure • Resting energy expenditure Determined by fat free mass(60-80% variability) Developmental regression of RMR(↑muscle-organ ratio) 79.2kcal/Kg 0-2.5 years-36kcal/Kg4-7 years-28.3kcal/Kg during adolescence-21kcal/Kg in adulthood) ◎fat mass-age-sex-physical activity can affect RMR Measured by indirect calorimetry (Vo2-CO2) • Thermal effect of food Energy cost is 10% of energy ingested • Voluntary energy expenditure (Non-exercise Associated Thermogenesis (30% of TEE)+ Volitional physical activity)

16. Genetic Factors • The human obesity gene map 2003 update identified more than 430 gene mutation affecting BMI, body –fat mass ,percentage of body fat ,abdominal fat ,fat-free mass , skin folds , RMR and neuroendocrinal components of energy balance

17. Effects of Certain Medications • Antacid pills • Anti-inflammatory • Beta blockers • Contraceptive pills • Statins • Cough drops • Antihistaminics

18. Medical Causes of Obesity • Hypothroidism • Cushing disease and syndrome • Polycystic ovarian syndrome

19. The world of lipid

20. Lipid metabolism

21. Lipids • Triglycerides (neutral fat) • Phospholipids • Cholesterol • Few others less important

22. Transportation of lipids

23. Triglycerides fat globules Bile Emulsified fat Pancreatic lipase Fatty acids and 2-monoglycerides Resynthesis Venous system Triglycerides Aggregate Chylomicrons Thoracic duct

24. Chylomicrons in the venous blood Capillaries of liver and adipose tissue Lipoprotein lipase Hydrolysis of triglycerides Fatty acids +glycerol Fat cells Resynthesis Triglycerides

25. Release of fat from fat cells Hydrolysis of triglycerides into FA + glycerol by • Low carbohydrate load to fat cells • Hormone sensitive lipase (HSL) On leaving fat cells ➞ FA ionize in the plasma ➞ immediately combines with albumin molecules (FFA or NEFA)

26. Free fatty acid (FFA ) • Concentration of FFA in the plasma during resting conditions is 15mg/ dl of total FA of .5gm • This small amount is the physiologically active because: • Every 2-3 minutes half of the plasma FFA is replased with new FA ◎almost all energy requirements of the body can be provided by oxidation of the transported FFA without using CHO or proteins 2. All the conditions that increase the rate of FA utilization also increase FFA conc up to 5 to 8 folds

27. The Fat Depots • Large quantities of fat are stored in 2 major tissues Adipose tissue and liver Adipose tissue is called fat depots

28. Adipose Tissue vs. Fat

29. Total body adipose tissue percentage

30. Traditional Adipose Tissue Classification • Classical anatomy was mainly organ-centered, without recognizingthe specialized organ-like functions of different tissues • Thiswas especially true of adipose tissue, which only recently hasbeen recognized as an "endocrine organ “ N Engl J Med .2001;345:1345 • Simple anatomic adipose tissue groupings :subcutaneous adipose tissue, organ-surrounding adiposetissue, interstitial adipose and adipose tissue in bone marrow • Adipose tissue is also named according to special biologicalfunctions, such as white, mammary gland, brown, and bone marrowadipose tissues

31. Recent proposed Classification of total body adipose tissue Shen et al,Obes Res.2003;11:1 Subcutaneous Internal Superficial Visceral Non- visceral Deep Intramuscular Perimuscular Orbital Intrathoracic Intraabdominopelvic Intrapricardial Intraperitoneal Extrapritoneal Extrapricardial Intraabdominal Intrapelvic Parametrial Retropubic Paravesical Retrouterine Pararectal Retrorectal Preperitoneal Retrroperitoneal

32. Dynamic state of storage fat • Exchange of fat between adipose tissue and blood : Because of rapid exchange of FFA Triglycerides in the fat cells are renewed approximately once every 2 to 3 weeks

33. Use of triglycerides for energy • Hydrolysis of triglycerides ➞ FA + glycerol • Entry of FA into mitochondria by carnitine shuttle system • Splitting of acetyl CoA from FA • Oxidation of acetyl CoA in citric acid cycle

34. The liver lipids The principal functions of liver in lipid metabolism • Degradation of fatty acids • Synthesize triglycerides from carbohydrates • Synthesize other lipids (cholesterol and phospholipids )

35. Formation of acetoacetic acid in the liver • Large share in the initial degradation of FA • FA➞ acetyl CoA ➞ 2 acetyl CoA + H2O ➞acetoacetic acid ➞ other cells for energy • Acetoacetic acid can also be converted to B-hydroxybuteric acid and acetone • Acetoacetic acid and B-hydroxybuteric acid diffuses through liver cell membranes to blood to other tissues for energy • Their transport is so rapid not more than 3 mg/dl except in!

36. Ketosis • The name acetoacetic acid consist of keto acid and 3 compounds called ketone bodies • Excess FA ➞ excess acetoacetic acid ➞ ketosis • Low carbohydrate load (DM,starvation or high fat diet) • Tremendous quantities of FA become available to liver for degradation ➞ excess keto acid and ketone bodies

37. Synthesis of triglycerides from carbohydrates • CHO either used for energy or stored as glycogen • However excess CHO will be converted to triglycerides (liver) to be trasported by VLDL to adipose tissue • Average person has almost 150 times as much energy stored in the form of fat as stored in the form of CHO • Each gram of fat gives 2.5 times calories as CHO

38. Fat sparing effect of carbohydrates • Excess of carbohydrates ➞ preffered metabolic fuel because : • ↑α-glycerophosophate ➞shift metabolism toward fat storage • FA synthesized more rapidly than they are degraded because of the vailabilty of acetyl CoA carboxylase ➞ converts acetyl CoA to FA ◎excess CHO in diet not only spares fat but also increases fat synthesis

39. Upper and Lower Body Adipose Tissue Function: A Direct Comparison of Fat Mobilization in males between 22 to 43years. Garry .Obes Res,2004

40. Objectives: Fat in the lower body is not associated with the same risk of cardiovascular disease as fat in the upper body. Is this explained by differences in the physiological functioning of the two depots? This study had two objectives: • to determine whether fat mobilization and blood flow differ between gluteal and abdominal adipose tissues in humans, and 2) to develop a new technique to assess gluteal adipose tissue function directly.

41. Research Methods and Procedures: They performed detailed in vivo studies of adipose tissue function involving the assessment of fat mobilization by measurement of adipose tissue blood flows, arterio-venous differences of metabolites across each depot, and gene expression in tissue biopsies in a small-scale physiological study.

42. Results: Gluteal adipose tissue has a lower blood flow (67% lower, p < 0.05) and lower hormone-sensitive lipase rate of action (87% lower, p < 0.05) than abdominal adipose tissue. Lipoprotein lipase rate of action and mRNA expression are not different between the depots. This is the first demonstration of a novel technique to directly investigate gluteal adipose tissue metabolism.

43. Discussion: Direct assessment of fasting adipose tissue metabolism in defined depots show that the buttock is metabolically "silent" in terms of fatty acid release compared with the abdomen.

44. Another study done by dora and published in obesity research journal confirned : • Abdominal adipocytes are more sensitive and responsive to beta adrenergic stimulation of lipolysis than gluteal adipocytes • Gluteal lipocytes have higher LPL activity than abdominal lipocytes This study was done on post menopausal females

45. Metabolic syndrome

46. What is metabolic syndrome? • Metabolic syndrome is a collection of health risks that increase the chance of developing heart disease, stroke, and diabetes. • The condition is also known by other names including Syndrome X, insulin resistance syndrome, and dysmetabolic syndrome.

47. What are these health risks? ATP III Guidelines WHO Guidelines Abdominal Obesity Waist CircumferenceWaist/Hip Ratio Men > 40 inches (102 CM)  >0.90 Women > 35 inches (88 CM)  >0.85 Other Variables Triglycerides150 mg/dL 150 mg/dL HDL-Cholesterol Men < 40 mg/dL <35 mg/dL  Women < 50 mg/dL <39 mg/dL Blood Pressure130/ 85 mm Hg >140/>90 mm Hg Fasting Glucose110 mg/dL 110 mg/dL WHO guidelines also include microalbuminuria (>20 µg/min or albumin:creatinine ratio >30 mg/g).

48. The pathogenesis of metabolic syndrome Complex interplay of a still largely unknown genetic background with environmental lifestyle- related factors

49. Environmental lifestyle-related factors: When we eat ,our bodies break down the food into its basic components ( protein-carbohydrates- fat), and absorbs them into blood stream  rise in blood sugar  pancreas will release insulin moves sugar into cells either burned for energy or stored away as fat in fat cells or glycogen in liver and muscles Years of dietery abuse in susceptible patients  malfunctioning of insulin sensors  hyperinsulinemia Continued dietery abuse  insulin sensors to sluggish  insulin resistance

50. Markers of insulin resistance : • Hypertriglyceridemia • HDL • Hypertension • Hyperinsulinemia • Abdominal obesity • Hyperglycemia • Recently Marjo etal , proven liver fat accumulation as an important marker • ( Obes Res 2002; 10: 859)