1. Fettsucht Lajos Szollár Semmelweis Universität Fakultät für Medizin Institut für Pathophysiologie 2006

3. Obesity  Definition of obesity: Increase of adipose tissue  Criteria of obesity, grade of severity  Broca-index, relatíve weight, ideal weight, body mass index  Frequency, geographical distribution, time-trends  Effects on mortality and morbidity  Consequences and complications  Classification of obesity  Hypertrophic-hyperplastic  Central-peripheral  Pathogenesis of obesity

4. Body fat in obesity

5. ENERGY RESERVES IN LEAN AND OBESE SUBJECTS (After Bray, 1976 ) Body weight 70 100 Fat (triglyceride) 15 564.840 40 1.506.240 Proteine (muscle) 6 100.416 7 117.152 Glycogen 0.07 1.170 0.07 1.170 kg kJ kg kJ Lean Obese

6. Obesity  Definition of obesity: Increase of adipose tissue  Criteria of obesity, grade of severity  Broca-index, relatíve weight, ideal weight, body mass index  Frequency, geographical distribution, time-trends  Effects on mortality and morbidity  Consequences and complications  Classification of obesity  Hypertrophic-hyperplastic  Central-peripheral  Pathogenesis of obesity

7. Clinically useful anthropometric methods  Broca-index: ideal weight=body height (cm)-100  Modified Broca-index: ideal weight=((body height (cm)-100))-10 %  Relatíve weight: actual weight / ideal weight x 100 obese > 120  BMI (Body Mass Index), Quetelet-index: body weight (kg) / body height 2 (m 2 ) desirable 30

8. BMI (body mass index)

11. Obesity  Definition of obesity: Increase of adipose tissue  Criteria of obesity, grade of severity  Broca-index, relatíve weight, ideal weight, body mass index  Frequency, geographical distribution, time-trends  Effects on mortality and morbidity  Consequences and complications  Classification of obesity  Hypertrophic-hyperplastic  Central-peripheral  Pathogenesis of obesity

14. Prevalence of Obesity Adults Worldwide 1998—World Health Organization 1998—Geneva, WHO

15. Prevalence of Overweight in Girls and Boys by Race and Age Ogden CL, et al. JAMA 2002;288:1730

17. Total Prevalence of Obesity in the U.S.: Men and Women (Ages 20-74 years) Prevalence % Flegal KM, et al. JAMA 2002;288:1724

19. Historic, current and projected obesity prevalence rates (BMI > 30) Kopelman, Nature 404:635, 2000

20. Obesity  Definition of obesity: Increase of adipose tissue  Criteria of obesity, grade of severity  Broca-index, relatíve weight, ideal weight, body mass index  Frequency, geographical distribution, time-trends  Effects on mortality and morbidity  Consequences and complications  Classification of obesity  Hypertrophic-hyperplastic  Central-peripheral  Pathogenesis of obesity

21. BMI and mortality

25. Obesity  Definition of obesity: Increase of adipose tissue  Criteria of obesity, grade of severity  Broca-index, relatíve weight, ideal weight, body mass index  Frequency, geographical distribution, time-trends  Effects on mortality and morbidity  Consequences and complications  Classification of obesity  Hypertrophic-hyperplastic  Central-peripheral  Pathogenesis of obesity

26. Mortality in obesity Cause Non- obese mortality=100 Men Women Diabetes mellitus 383 372 Gallstones 206 284 Post surgery 200 300 Cardiovascular and kidney 149 177 Accidents 111 135 Malignant diseases 97 100 Suicide 79 73 Tuberculosis 21 35

27. Health Consequences of Obesity Cardiovascular disease Dyslipidemia Type II diabetes mellitus Hypertension Cancer, some common types Degenerative joint disease Gallstones Gynecologic irregularities Sleep apnea syndrome

30. 26 -Year Incidence/10,000 of Coronary Heart Disease in Women and Men by BMI BMI Levels Hubert HB et al. Circulation 1983;67:968-977.

32. BMI and relative risk (a=woman b=men) Kopelman, Nature 404:635, 2000

34. Type 2 diabetes and obesity

36. Osteoarthrosis and obesity

37. Infertility and obesity

38. Gout and obesity

39. Obesity and ovarian cancer

40. Consequences of obesity  Cardiovascular system  Arteriosclerosis  Congestív heart failure, cor pulmonale  Venous disorders, thrombophlebitis  Hypertension  Diabetes mellitus  Alveolar hypoventilation (Pickwick-syndrome)  Gastrointestinal disorders (fatty liver,gallstones)  Kidney  Arthrosis  Endocrine system (reproductive and menstrual disorders, toxaemia)  Other (intertrigosus dermatosis, hiatus hernia, endometrial carcinoma)

42. Obesity  Definition of obesity: Increase of adipose tissue  Criteria of obesity, grade of severity  Broca-index, relatíve weight, ideal weight, body mass index  Frequency, geographical distribution, time-trends  Effects on mortality and morbidity  Consequences and complications  Classification of obesity  Hypertrophic-hyperplastic  Central-peripheral  Pathogenesis of obesity

50. Assessment of accumulation of abdominal fat by measurement of waist at mid-distance between bottom of rib cage and iliac crest. Amount of visceral adipose tissue that can be assessed by CT can be estimated by waist measurement Despres et al. BMJ 322:716,2001

51. The Metabolic Syndrome and Associated CVD Risk Factors Insulin Resistance Atherosclerosis Endothelial Dysfunction Hypertension Abdominal obesity Hyperinsulinaemia Dyslipidaemia high TGs small dense LDL low HDL-C Diabetes Hypercoagulability Deedwania PC. Am J Med 1998;105(1A);1S-3S.

52. HBP Inflam- mation  Insulin Diabetes  TG Dense LDL-C Low HDL-C  Coag. Interrelationships Between Insulin Resistance and Atherosclerosis Insulin Resistance Endothelial dysfunction Atherosclerosis Obesity

54. Obesity  Definition of obesity: Increase of adipose tissue  Criteria of obesity, grade of severity  Broca-index, relatíve weight, ideal weight, body mass index  Frequency, geographical distribution, time-trends  Effects on mortality and morbidity  Consequences and complications  Classification of obesity  Hypertrophic-hyperplastic  Central-peripheral  Pathogenesis of obesity

55.  Pathogenesis of Obesity  „Pure” Overeating  Disturbances in Appetite Regulation  Disturbances in Intermediate Metabolism  Defective Thermogenesis  „Thrifty” Gen Expression  Treatments Available  Diet  Drug  Surgery

57. Energy intake and demand in developped countries in the XX. Century Energy intake Energia demand kcal

64. Prevalence of overweight and intake of fat

66. Ludwig

70. Energy intake and demand in developped countries in the XX. Century Energy intake Energia demand kcal

72. Obesity and lifestyle

73. Percent of Adults Physically Inactive Age-Groups Percent Source—Advance Data from Vital and Health Statistics. #325, April 7, 2002 Ages 45-54 Ages 55-64 Percent of Adults with Diabetes

75.  Pathogenesis of Obesity  „Pure” Overeating  Disturbances in Appetite Regulation  Imbalance in Energy Expenditure  Defective Thermogenesis  „Thrifty” Gen Expression  Treatments Available  Diet  Drug  Surgery

76. Hypothalamic areas implicated in eating behaviour

77.  Pathogenesis of Obesity  „Pure” Overeating  Disturbances in Appetite Regulation  Imbalance in Energy Expenditure  Defective Thermogenesis  „Thrifty” Gen Expression  Treatments Available  Diet  Drug  Surgery

79. „Thrifty” gen and obesity

80. Genes and environment in type 2 diabetes and atherosclerosis

81. Pima Indians Thrifty genes

82. Thermogenesis in men

87.  Pathogenesis of Obesity  „Pure” Overeating  Disturbances in Appetite Regulation  Imbalance in Energy Expenditure  Defective Thermogenesis  „Thrifty” Gen Expression  Leptin  Treatments Available  Diet  Drug  Surgery

92. Monogenic obesity in rodents  Spontaneous  Lack of leptin (ob/ob)  Leptin receptor defect (db/db)  Ectopic Agouti expressio (Ay)  „Fat rich” (fa/fa)  Genetically manipulated  Serotonin 2C-receptor KO  Melanocortin-4 receptor KO  Agouti related protein (AgRP) hyperexpressio  Neuropeptid Y (NPY) receptor KO  CRH hyperexpession  Bombesin B-3 receptor KO  Glut-4 hyperexpression

93. The ob/ob mouse and its normal counterpart

94. Serum leptin and body fat

95. Soluble leptin receptors, immunoreactive leptin and BMI Shimizu et al., Nutrition 18:309 (2002)

96. Hypothetical risk of obesity Hill et al., Science 280:1371 (1998)