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

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

Body fat in obesity

ENERGY RESERVES IN LEAN AND OBESE SUBJECTS (After Bray, 1976 ) Body weight Fat (triglyceride) Proteine (muscle) Glycogen kg kJ kg kJ Lean Obese

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

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

BMI (body mass index)

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

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

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

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

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

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

BMI and mortality

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

Mortality in obesity Cause Non- obese mortality=100 Men Women Diabetes mellitus Gallstones Post surgery Cardiovascular and kidney Accidents Malignant diseases Suicide Tuberculosis 21 35

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

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

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

Type 2 diabetes and obesity

Osteoarthrosis and obesity

Infertility and obesity

Gout and obesity

Obesity and ovarian cancer

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)

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

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

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.

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

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

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

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

Prevalence of overweight and intake of fat

Ludwig

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

Obesity and lifestyle

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

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

Hypothalamic areas implicated in eating behaviour

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

„Thrifty” gen and obesity

Genes and environment in type 2 diabetes and atherosclerosis

Pima Indians Thrifty genes

Thermogenesis in men

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

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

The ob/ob mouse and its normal counterpart

Serum leptin and body fat

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

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