Abstract
Obesity is an epidemic disease that threatens to inundate health care resources by increasing the incidence of diabetes, heart disease, hypertension, and cancer. These effects of obesity result from two factors: the increased mass of adipose tissue and the increased secretion of pathogenetic products from enlarged fat cells. This concept of the pathogenesis of obesity as a disease allows an easy division of disadvantages of obesity into those produced by the mass of fat and those produced by the metabolic effects of fat cells. In the former category are the social disabilities resulting from the stigma associated with obesity, sleep apnea that results in part from increased parapharyngeal fat deposits, and osteoarthritis resulting from the wear and tear on joints from carrying an increased mass of fat. The second category includes the metabolic factors associated with distant effects of products released from enlarged fat cells. The insulin-resistant state that is so common in obesity probably reflects the effects of increased release of fatty acids from fat cells that are then stored in the liver or muscle. When the secretory capacity of the pancreas is overwhelmed by battling insulin resistance, diabetes develops. The strong association of increased fat, especially visceral fat, with diabetes makes this consequence particularly ominous for health care costs. The release of cytokines, particularly IL-6, from the fat cell may stimulate the proinflammatory state that characterizes obesity. The increased secretion of prothrombin activator inhibitor-1 from fat cells may play a role in the procoagulant state of obesity and, along with changes in endothelial function, may be responsible for the increased risk of cardiovascular disease and hypertension. For cancer, the production of estrogens by the enlarged stromal mass plays a role in the risk for breast cancer. Increased cytokine release may play a role in other forms of proliferative growth. The combined effect of these pathogenetic consequences of increased fat stores is an increased risk of shortened life expectancy.