Leptin resistance

Abstract

Leptin is primarily produced by adipocytes. Its plasma concentration varies in proportion to fat mass. Binding of leptin to its receptors in the hypothalamus and brain stem orchestrates the activity of neuroendocrine ensembles that inhibit food intake and increase energy expenditure. Loss of function mutations of the leptin- or leptin receptor gene are associated with obesity and insulin resistance in rodents. Leptin deficient humans are also morbidly obese, which indicates that leptin plays a critical role in the control of energy balance in man as well as in rodents. Circulating leptin levels are high in most obese humans and apparently do not act to reduce adipose stores to their 'normal' size. Emerging evidence indicates that high fat feeding induces leptin resistance in rodents. Clinical evidence supports the notion that obese humans are leptin resistant as well. Leptin resistance may not only explain the propensity of people to grow obese, it may also underlie various metabolic features of obesity. This paper reviews current perceptions of the causes and consequences of leptin resistance in rodents and man.