Obesity and the Regulation of Energy Balance.

Obesity is defined medically as a state of increased body weight, more specifically adipose tissue, of sufficient magnitude to produce adverse health consequences. There has been an alarming increase recently in the prevalence of this heterogeneous group of disorders in the Western world (Kuczmarski et al., 1994). Fully one-third of the American population is now considered obese, and the prevalence of obesity in children is escalating dramatically, presaging even greater medical harm in the decades to come (Troiano and Flegal, 1999). What accounts for this epidemic of energy storage? Body weight and composition, and the storage of energy as triglyceride in adipose tissue, are determined by the interaction between genetic, environmental, and psychosocial factors. These influences ultimately act by changing the energy balance equation, that is, the long-term balance between energy intake and expenditure. Physiologic studies had previously suggested that body weight and energy stores are homeostatically regulated, with either weight loss or gain producing concerted changes in energy intake and expenditure that resist the initial perturbation. Recent cloning of several obesity genes has revealed the initial molecular components of a coherent physiologic system for energy homeostasis (Barsh et al., 2000). Studies of obesity pathogenesis must now attempt to explain the disorder in the context of this physiologic system.