Leptin

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Leptin

Leptin is an adipocyte hormone that functions as the afferent signal in a negative feedback loop regulating body weight. The levels of protein are increased in several genetic and environmentally induced forms of rodent obesity and in obese humans. Leptin is not the only afferent signal that regulates food intake and body weight. The systems that control feeding behavior and energy balance appear to be comprised of a short-term and a long-term system. The short-term system regulates meal pattern and feeding throughout the day. Previous work indicates that changes in plasma glucose concentration, body temperature, plasma amino acids, cholecystokinin, and other hormones can all modulate meal patterns.12 The long-term system balances food intake and energy expenditure and thus plays a dominant role in ultimately regulating the size of the body’s energy stores. Leptin appears to function largely within the long-term system and influences the quantity of food consumed relative to the amount of energy that is expended.

Leptin resistance has been implicated in the pathogenesis of obesity-related complications involving abnormalities of lipid metabolism that resemble those of old age. Because deficiency of and unresponsiveness to leptin result in the ectopic overaccumulation of lipids secondary to underexpression of PPARa and the enzymes of FA oxidation, it seemed possible that loss of sensitivity to leptin might be a cause of age-related ectopic accumulation of unoxidized lipids. The report that activators of PPARa can correct age-related dysfunction of redox balance would be consistent with the posit that the cellular damage is, at least in part, the result of FA excess secondary to leptin resistance.