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 / m 2 ) 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/m 2 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 screening measure that can be used to identify overweight and obese patients. Men with NC <37 cm and women with NC <34 cm are not to be 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 1.Appetite and its motor component ( medullary NTS) 2.Autonomic nervous system,with its 2 pathways: a. sympathetic limb b. parasympathetic limb 3.Three components of total energy expenditure a.Resting energy expentiture (50 to 65% ) b.Thermal effect of food c.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 M 3 receptors ➞ acetylcholine ➞ depolarization of beta cell ➞ calcium influx ➞ hyperinsulinemia

15. 3.Components of energy expenditure 1.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 (Vo 2 -CO 2 ) Thermal effect of food Energy cost is 10% of energy ingested 3.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 1.Triglycerides (neutral fat) 2.Phospholipids 3.Cholesterol 4.Few others less important

22. Transportation of lipids

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

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

25. Release of fat from fat cells H ydrolysis of triglycerides into FA + glycerol by 1.Low carbohydrate load to fat cells 2.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: 1.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. AgeMalesFemales 10-3012-1820-26 31-4013-1921-27 41-5014-2022-28 51-6016-2022-30 6117-2122-31 Total body adipose tissue percentage

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

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

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 1.Hydrolysis of triglycerides ➞ FA + glycerol 2.Entry of FA into mitochondria by carnitine shuttle system 3.Splitting of acetyl CoA from FA 4.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 : 1. ↑ α-glycerophosophate ➞ shift metabolism toward fat storage 2.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: 1)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 : 1.Abdominal adipocytes are more sensitive and responsive to beta adrenergic stimulation of lipolysis than gluteal adipocytes 2.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 Circumference Waist/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)

51. Obesity Lets walk through the fat metabolism pathway and follow the flow of fat molecules: Fat travels in the form of triglycerides  at cells  ezymatic breakdowen  fatty acids enter the cells mitochondria  breakdowen fat  in order to enter mitochondria,fats need carnitine  insulin inhibitsFat- carnitine shuttle system  fats move back into blood Glucagon accelerates this shuttle system Muscle,liver, kidney, lung, heart and other cells break down fat

52. Two enzyme systems on the surface of fat cells regulated by insulin and glucagon Insulin stimulates lipoprotein lipase that transports fatty acid into fat cells Glucagon stimulates hormone sensitive lipase that releases the fat from fat cells into the blood Although we cannot control lipoprotein lipase directly, we can control It indirectly by cotrolling the metabolic hormones, insulin and glucagon Fat cells merely store the fat molecules !

53. Functions of Cholesterol : Adrenal hormones and sex hormones Main component of bile acids Essential for normal growth and development of brain and nervous tissue Gives the ability of skin to shed water Precursor of vitamine D3 in the skin Normal growth and repair of tissues Transportation of triglycerides DYSLIPIDEMIA

54. Where does cholesterol come from? 80 % comes from the body itself, every cell in the body is capable of making its own cholesterol, most don’t and rely instead on that made in the liver and skin. Cholesterol and triglycerides are insoluble in blood Lipoproteins are envelops that enclose cholesterol and triglycerides Making them soluble in blood,so that they can be transported to tissues

55. Sequence of events in the life of lipoproteins Liver Makes and release VLDL TRIGLYCERIDES WITH CHOLESTEROL TRI AND CHOLES MATURE VLDL Triglycerides Released to blood And tissues Cholesterol Bulk +tri LDL HDL Scavenges cholesterl From tissues carries Through blood Hands it off to VLDL More triglycerides release Removed by liver CholesteroL rich LDL Released to tissues Deposited in coronary arteries

56. When the level of cholesterol inside the cells falls  LDL receptors Attach to the surfaces of the hepatic cells invaginate LDL cholesterol By endocytosis Obese patients with insulin resistance have LDL receptors dysfunction Cholesterol synthesis inside the cells depends on an enzyme named 3- hydroxy-3 methyl-glutaryl-coenzyme A reductase Couple of hormones affect the activity of the rate limiting enzymeHMG-CoA reductase INSULIN AND GLUCAGON

57. Diet and cholesterol quiz

58. Patient with the following finding Total cholesterol: 240 LDL : 160 HDL:35 Total/ HDL: 6.85 LDL/HDL: 4.57 Diet 1Diet 2 Total cholesterol159 mg/dl191 mg/dl LDL111 mg/dl139 mg/dl HDL32 mg/dl42 mg/dl Total /HDL4.974.55 LDL/HDL3.473.31 Which is better?

59. Hypertension Data from NHANES III show that the (age – adjusted prevalence) Of high blood pressure increases progressively with higher levels Of BMI in men and women High blood pressure is defined as SBP 140 mm Hg or MBP  90 mm Hg or currently taking antihypertensives

60. What is the etiology that connects obesity and hypertension? Hyperinsulinemia and insulin resistance

61. Mechanism 1.Increased sodium retention 1.Increased sympathetic nervous system activity 1.Alteration in the mechanics of blood vessels

62. However It is known that weight loss is associated with  vascular resistance,total blood volume and cardiac output Improvement in hyperinsulinemia and insulin resistance  sympathetic nervous system activity Suppression of the activity of renin angiotensin aldosterone system Recently,serum angiotensin converting enzyme activity declines with modest weight loss. The precise mechanism whereby weight loss results in a decrease in Blood pressure is unknown.

63. Type II Diabetes mellitus It represents 90% of all cases of diabetes. Requires years of underlying metabolic disturbance before symptoms become apparent The development and diagnosis usually follows weight gain In Type I and Type II diabetes blood sugar is elevated but for different reasons Type I there is no insulin to hold it down by moving it into cells

64. Type II the cells become resistant to insulin that even large amounts cant adequately move the sugar into cells In early stages there is hyperinsulinemia,later pancreatic beta cells wear out from constantly producing insulin under stimulation of hyperglycemia Resistin is a protein secreted by fat cells as a signal from adipose tissue linking obesity to insulin resistance and type II diabetes Liese et al, Eur J Nutr.2001;40:282 Increased White blood cell count is correlated with insulin resistance in diabetic obese females Pannacciulli et al,Obes Res.2003;11:1232

65. Coronary artery disease Observational studies have shown that overweight,obesity, and VAT are directly related to cardiovascular risk factors (  cholesterol,  LDL,  triglycerides, hypertension,  fibrinogen,hyperinsulinemia,  HDL, plasminogen activator inhibitor ) RECENTLY Complement 3 and acute phase proteins is the immunological link between central obesity and CHD The term "Syndrome X" refers to a heart condition where chest pain and electrocardiographic changes that suggest ischemic heart disease are present, but where there are no angiographic findings of coronary disease.

66. Recent studies have shown that risks of nonfatal myocardial infarction and CHD death increase with increasing levels of BMI In British, Swedish, Japanese and US populations, CHD incidence increased at BMIs above 22 and an increase of 1 BMI unit was associated with 10 % increase in the rate of coronary events Recent study has found that obese CHD patients are younger and and are hospitalized more frequently during the first 10 years of their illness than the non-obese

67. Obesity and cardiac dysrhythmias (prolonged Q-T interval) Q-T interval is usually measured in lead II, and is corrected for heart rate. Q-Tc= measured Q-T  square root of R-R interval Prolonged Q-T interval reflects prolonged repolarization of the ventricle Proposed mechanism is increased SNS activity Recent study had found that Prolonged Q-T interval is associated with abnormal WHR,higher levels of FFA and hyperinsulinemia in obese women. Wight loss leads to normalization of Q-Tc with attenuation of hyperinsulinemia Esposito et al,Obes Res.2003;11:653-659

68. Oxidant Stress Imbalance Between Formation Of Reactive oxygen/nitrogen species (ROS/RNS) And Antioxidants

69. Pathologic stress  Induces monocytes to release mediators (TNF and interleukins 1-6-8)  Activates PMNs  Release ROS(superoxide (O 2 ·- ), hydrogen peroxide, hypochlorite, nitric oxide (NO), hydroxyl radical  Induce tissue injury by: 1.damaging DNA 2.Cross linking cellular proteins 3.Peroxidation of membrane lipids  Diminishing membrane fluidity Increasing membrane permeability

70. Oxidant Stress and Obesity Adipocytes and preadipocytes have been identified as sources of inflammatory cytokines : including TNF , interleukin (IL)1-ß, and IL-6. Stimuli capable of inducing cytokine release from adipocytes may include: lipopolysaccharides, intracellular triglycerides, and catecholamines

72. We could predict that: The accumulation of intracellular triglycerides or tissue adiposity promotes increased oxidant stress Therefore reduction of total body fat through diet and/or exercise may be an effective means of reducing systemic inflammation and oxidant stress. Consistent with this prediction Reductions in plasma markers of oxidant stress and in ROS generation by isolated leukocytes have been observed after 4 weeks of energy restriction and weight loss. Dandona et al. J Clin Endocrinol Metab,2001; 86:355-363

73. Good news Physical activity  Decreases adipose derived inflammatory mediators Activates signaling pathways that lead to increased synthesis of intracellular antioxidants and antioxidant enzymes and decreased ROS production Miyazaki et al, Eur Appl Physiol.2001; 84:1-6 Pischon et al, Obes Res.2003;11:1055

74. A novel pathway to the manifestations of metabolic syndrome

76. Obesity And Diseases

77. Obesity and cancer Strong risk factor for esophageal cancer Uterine and gall bladder cancer in obese women High risk for colon and prostate cancer in obese males Breast cancer for obese postmenopausal women

78. What is the link between obesity and cancer 1.Hyperinsulinemia and insulin resistance 2.Oxidant stress

79. Obesity and osteoarthritis Degenerative process affecting articular cartilage Predisposing factors: advancing age+ genetic predisposition +obesity Common affected sites :knees and hips then cervical spine and lower lumbar area Pathogenesis : Forces across the hip and knee during walking and stair climbing are 2 to 4 times normal body weight and each extra weight will multiply these forces on the joints NHNES showed that adults with BMI>30 have 4 folds higher prevalence than those <30 Leptin overexpression in arthritic joint is related to cartilage destruction and correlated with BMI

80. Obesity and gout Is a metabolic disorder of purine metabolism Either primary :genetic defect in purine metabolism Or secondary to: chemotherapeutic drugs, renal impairment, thiazide diuretics,alcohol abuse and purine rich foods (liver,kidney,peas,lentils,red meat) Clinical picture :crystals of uric acid (tophi) build up forming large deposits in : metatarsophalyngeal joints, wrist,elbow,knee,and extraarticular tissues(nephrolithiasis, myocardium, aortic valve and extradural spinal region. Recently :insulin resistance is the precursor of gout (journal of american medical association Diet regimens that lead to gout: any regimen that results in a rapid weight loss will increase uric acid 2-3 folds

81. Obesity and gallstones The incidence of gallstones is significantly higher in obese women and men The risk of stone formation is also high if a person loses weight too quickly

82. Obesity and lungs Strong risk factor for adult onset asthma (imbalance between good eicosanoids and bad eicosanoids) Increased risk of hypoxemia and detrimental work of breathing Pickwickian syndrome

83. Obesity and sleep apnea and sleep disorders Obese tend to fall asleep faster and sleep longer during the day At night,it takes them longer to fall asleep they sleep less than others. When the upper airways relaxes and collapses at intervals during sleep,thereby temporary blocking the passage of air (sleep apnea) Symptoms :morning headach, fatigue and irritability Side effects :dysrhythmias,stroke,right sided heart failure and car accidents Sleep apnea deprives patients from REM sleep REM sleep: the dreaming phase of sleep, necessry for emotional wellbeing Obesity leads to sleep apnea which leads to loss of REM sleep which leads to raising of BMI

84. OBESITY AND EATING DISORDERS Binge eating : about 30% of obese are binge eaters,who typically consume 5000 to 15000 calories in one sitting To be diagnosed as a binge eater,person has to binge twice a week for 6 months Bulimia : binge eating followed by purging in order to lose weight Anorexia : severe weight loss and is life threatening

85. Types and approaches to obesity treatment

86. 1.Do it yourself programs 2.Non-clinical programs 3.Clinical programs Individual heath care professional Multidisciplinary group of professionals (physician,dietitian,exercise and psychological counselors )

87. Evaluation of the program by the physician The match between the program and the consumers The soundness and safety of the program: 1.Assessment of physical health and psychological status 2.Attention to diet and pharmacotherapy 3.Attention to physical activity 4.Program safety Outcome of the program 1.Long-term weight loss 2.Improvement in obesity related comorbidities 3.Improved heath practice 4.Monitoring adverse effects that might result from the program

88. Caloric restriction Normal caloric intake 20-25 calories for each Kg of the body weight or According to Harris-Benedict equation: for males RMR= 66.4+ 13.8 W + 5H – 6.8A for females RMR= 665+ 9.6W+ 1.8H – 4.7A W=weight (kg), H = height (cm), and A= age (yr) e.g. weight : 120 kg H= 175 A=35 RMR= 66.4 + 13.8(120)+5(175) – 6.8(35)=2359.5 Less than 500 calories deficit per day ➞ weight loss of.5 Kg per week

89. Side effects of very low caloric diets < RMR Rebound effect ( leptin) Insufficient vitamines (ADEK) and minerals (Ca,zinc,iron and folic acid) Fatigue,intolerance to cold,hair loss, gall stone formation,gout, and menstrual irregularities Hypokalemia due to diuresis ➞ arrhythmias Hyponatremia ➞ fatigue, dizziness, confusion and coma Constipation (absence of insoluble fibres)

90. Macronutrient composition of diets

91. Traditionally,a low fat –high carbohydrate diet has been recommended to help obese patients lose weight National institute of health,national heart,lung and blood institute,and national institutes of diabetes and digestive and kidney diseases.clinical guidelines on the identification,evaluation,and treatment of overweight and obesity in adults.Bethesda,MD:NIH;1998

92. Data from a recent meta analysis that evaluated randomized clinical trials that compared fat- restricted and calorie restricted diets has found no difference in weight loss between diet groups Pirozzo S,etal.Cochrane Database Syst Rev.2002;2:Cd003640

93. The results from four randomized controlled trials that compared the effect of low carbohydrate diet with a low fat diet on body weight in adult obese subjects have recently been published Brehm, et al. (2003) A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women J Clin Endocrinol Metab. 88,1617-1623 Samaha, et al (2003) A low-carbohydrate as compared with a low-fat diet in severe obesity N Engl J Med. 348,2074-2081 Foster, et al (2003) A randomized trial of a low-carbohydrate diet for obesity N Engl J Med. 348,2082-2090 Yancy, WS,et al. (2004) A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: a randomized, controlled trial Ann Intern Med. 140,769-777 Stern, et al (2004) The effects of low-carbohydrate versus conventional weight loss diets in severely obese adults: one-year follow up of a randomized trial Ann Intern Med. 140,778-785

94. A consistent difference in weight loss at 6 months has been observed between groups across studies; subjects randomized to the low-carbohydrate diet lost 4 to 5 kg more weight than those randomized to the low-fat diet. However, weight loss was no different between groups at 1 year. In addition, in subjects who had type 2 diabetes, there were greater improvements in fasting blood glucose concentrations and insulin sensitivity with a low- carbohydrate than with a low-fat diet. The data from these studies has also found greater improvements in serum triglyceride and high-density lipoprotein-cholesterol concentrations, but not in serum low-density lipoprotein-cholesterol concentrations, in the low-carbohydrate than the low- fat group.

95. Mitochondrial uncouplings All UCPs may lower mitochondrial ATP production through respiratory uncoupling,thus stimulating substrate oxidation in mitochondria Ricquier D, etal. Biochem J.2000;345:161- Fink BD,etal. J Biol Chem.2002;277:3918 In transgenic mice,high fat diet stimulates respiratory uncoupling in white adipose tissue and may lower plasma lipids by inducing fat oxidation. Martin R,etal.Obes Res.2005;13:835.

96. Energy Density Definition : the energy (kilocalories) present in a certain weight (grams) of food. It can affect the total caloric intake. Energy-dense foods are usually high in fat (e.g.,butter) and/or are dry (e.g.,fruits) Moreover, the results of short-term studies have suggested that manipulating energy density might be a useful approach to noncognitively regulate total energy intake

97. At present, it is unlikely that one diet is optimal for all overweight or obese persons, and dietary guidance should be individualized to allow for specific food preferences and individual approaches to reducing weight.

98. Walking is metabolically expensive for obese : 1.Greater body mass and heavier legs 2.Decreased stability,wider stance and wider lateral leg swing. Energy cost of walking is 20-100%greater for obese Walking slower for a set distance is an appropriate exercise recommendation for weight management prescription in obese adults Raymond,etal. Obes Res.2005;13:891

99. Spot reduction Mentioned to be condemned

100. Why treat overweight and obesity? Not only to improve the BODY IMAGE But also to reduce the OBESITY –RELATED COMORBIDITIES