The Role of Leptin in Human Obesity and Disease: A Review of Current Evidence

PURPOSE: To review recent advances in the pathophysiology and potential clinical applications of leptin, an adipose tissue-derived hormone. DATA SOURCES: A MEDLINE search of the literature on leptin and the bibliographies of relevant papers. STUDY SELECTION: All 1320 publications on leptin. DATA EXTRACTION: All identified articles were reviewed. Cited publications were selected on the basis of study quality and relevance to human obesity and disease. DATA SYNTHESIS: Leptin is a 16-kilodalton adipocyte-derived hormone that circulates in the serum in the free and bound form. Serum levels of leptin reflect the amount of energy stored in adipose tissue. Short-term energy imbalance as well as serum levels of several cytokines and hormones influence circulating leptin levels. Leptin acts by binding to specific receptors in the hypothalamus to alter the expression of several neuropeptides that regulate neuroendocrine function and energy intake and expenditure. Thus, leptin plays an important role in the pathogenesis of obesity and eating disorders and is thought to mediate the neuroendocrine response to food deprivation. Phase I and II trials recently showed that leptin administration to humans is safe, and ongoing phase III trials are assessing the efficacy of leptin as a treatment for obesity and related disorders. Availability of leptin or smaller and more soluble leptin analogues for clinical studies in humans is expected to significantly advance understanding of the mechanisms underlying energy homeostasis in humans. CONCLUSIONS: Leptin is significantly broadening our understanding of the mechanisms underlying neuroendocrine function, body weight, and energy homeostasis. Elucidation of these mechanisms is expected to result in the development of novel therapeutic approaches for obesity and eating disorders.