Obesity is epidemic in the United States. Approximately 25% of the U.S. population older than the age of 20 is clinically obese. Because it is highly correlated with an increased incidence of several disease, it is important to define and recognize it to understant its causes and to be able to initiate appropriate measures to prevent it or to treat it.



How does one measure fat accumulation? There are several highly technical ways to approximate the measurement but for practical considerations the following ones are commonly used:

Some expression of weight in relation to height especially the measurement referred to as the body mass index

Skinfold measurements

Various body circumferences particularly the ratio of the waist to hip circumference

The etiology of obesity is complex and incompletely understood. However, simply put obesity is a disorder of energy balance. When food derived energy chronically exceeds energy balance. When food derived energy chronically exceeds energy expenditure the excess calories are stored as triglycerides in adipose tissue. The two sides of the energy equation, intake and expenditure are finely regulated by neural and hormonal mechanisms. In most individual when food intake increases, so does the consumption of calories and vice versa. Hence body weight is maintained within a narrow range for many years. Apparently this fine balance is maintained by an internal set point or lipostat that can sense the quantity of the energy stores and appropriately regulate the food intake as well as the energy expenditure. The molecular natue of the lipostat remained obscure for many years but starting in 1994.

It is now established that adipocytes communicate with hypothalamic centers that control appetite and energy expenditure by secreting a polypeptide hormone called leptin. Leptin acts as an antiobesity factor a notion that is buttressed by the studies of mice with mutations in the leptin gent. Leptin dificient mice are massively obese; the administration of leptin reduces their food intake and increases energy expenditure thus tending to ameliorate obesity. Leptin mediates its effects by binding to and activating leptin receptors in the hypothalamus. In experimental animals triggering of the leptin receptor inhibits appetite and increases energy expenditure physical activity and production of heat. Thermogenesis is controlled at least in part by leptin receptor mediataed hypothalamic signals that increase the release of norepinephrine from sympathetic nerve endings in the adipose tissue. The fat cells express ?-adrenergic receptors that when stimulated by norepinephrine cause fatty acid hydrolysis and also uncouple energy production from storage. Thus the fats are literally burned and the energy so produced is dissipated as heat. There are other catabolic effects mediated by leptin, all transduced by its hypothalamic receptor which in turn communicates with other endocrine glands through the hypothalamic- pituitary axis. The role of the leptin leptin receptor system in the regulation of body weight is also supported by the observation that mutant mice lacking leptin receptors are massively obese. Unlike the case with leptin deficient mice, the in leptin receptor deficient mice cannot be corrected by leptin admin istration. Indeed, leptin levels are markedly elevated in db.db mice. In these mice obesity occurs because the leptin mediated afferent signals impinging on the hypothalamus fail to regulate appetite and energy expenditure.

Because the uncoupling of the leptin leptin receptor system can give rise to obesity in mice much interest is focused on the effectors of leptin action in the hypothalamus. Prominent among the hypothalamic mediators of leptin signaling is neuropeptide Y. This polypeptide increases appetite and inhibits sympathic activity and the production of heat, thus favoring weight gain. It is postulated that leptin deficiency causes obesity by increasing the production of NPY and conversely signaling through the leptin receptor inhibits the synthesis of NPY. Despite compelling data for a role of NPY as the mediator of leptin action, animals genetically engineered to lack NPY do not have abnormalities in feeding behavior and leptin is still effective in these NPY knockout mice. Thus it seems that leptin must have other target in the hypothalamus and additional effector pathways that are regulated by leptin have been discovered.

, particularly central obesity increases the risk for a number of conditions including diabetes , hypertension, hypertriglyceridemia, low HDL cholesterol and possibly coronary artery disease. The mechanisms underlying these associations are complex and likely ot be interrelated. Obesity for instance is associated with insulin resistance and hyperinsulinemia important features of non insulin dependent or type 2 diabetes and weight loss is associated with improvement. It has been speculated that excess insulin in turn may play a role in the retention of excess insulin, in turn may play a role in the retention of sodium expansion of blood volume, production of excess nonrepinephrine, and smooth muscle proliferation that are the hallmarks of hypertension. Regardless of whether these pathogenic mechanisms are actually operative the risk of developing hypertension among previously normontensive persons increases proportionately with weight.