OBESITY - GENES, GLANDS OR GLUTTONY

Distribution as well as amount of fat has health implications; central abdominal fat seems to be the major contributor to insulin resistance and risk of diabetes, hypertension and cardiovascular disease. Physic al activity and diet affect overall adiposity; moreover, exercise spec ifically reduces visceral fat. The sexes differ in fat distribution; i n particular, pre-menopausal women, despite greater overall adiposity, have much less visceral fat than men. There is a strong genetic deter mination of overall obesity and central abdominal adiposity. Genes reg ulating obesity (e.g. Ob) could modulate appetite, satiety, metabolic rate or physical activity. Moderate obesity probably results from inte raction between genetic predisposition and an environment of abundant calories and reduced physical activity. Single gene mutations are bein g identified in a few morbidly obese people; however, the common genet ic predisposition for obesity may relate to more subtle variations in regulatory controls. Diet and exercise are effective for some, but the response is often disappointing. Definition of pathways controlling a ppetite, metabolic rate and lipid metabolism may generate improved pha rmacological compounds. Education and availability of lower-energy foo ds may help, but more radical approaches may be needed, such as enviro nmental restructuring to increase physical activity. The problem is gr eat, but failure will mean intolerably increased health costs.