Regulation of metabolism and body fat mass by leptin

The relative stability of body weight over the long term and under a variet y of environmental conditions that alter short-term energy intake and expen diture provides strong evidence for the regulation of body energy content. The lipostatic theory of energy balance regulation proposed 40 years ago th at circulating factors, generated in proportion to body fat stores, acted a s signals to the brain, eliciting changes in energy intake and expenditure. The discovery of leptin and its receptors has now provided a molecular bas is for this theory. Leptin functions as much more than an adipocyte-derived signal of lipid stores, however. Although suppression of food intake is an important centrally mediated effect of leptin, considerable evidence indic ates that leptin also functions both directly and indirectly, via the brain , to orchestrate complex metabolic changes in a number of organs and tissue s, altering nutrient flux to favor energy expenditure over energy storage.