M.A. Pelleymounter Pages 85 - 98 ( 14 )
The regulation of body weight is a complex phenomena that is still poorly understood. It is generally accepted that body weight and adiposity are maintained through a feedback mechanism involving central nervous system integration of peripheral signalling pathways. The recently cloned Ob gene, which is synthesized in adipose tissue, may provide information to the central nervous system about adiposity. It can be measured in serum, and correlates with adiposity. In addition, Ob receptors are localized in the hypothalamus, a brain area associated with control of appetite and metabolism. Finally, exogenous administration of the Ob gene product, leptin, has been shown to reduce body weight, food consumption and adiposity in obese mice lacking functional leptin (ob/ob). Recent work, however, has suggested that the role of leptin may be more complex than that of a peripheral feedback signal of adiposity level. For example, leptin may play a role in starvation/refeeding, and may have direct effects on peripheral tissues. The impact of these findings on theories about the physiology and mechanism of action for exogenous leptin are discussed in this review.