Regulation and possible significance of leptin in humans: leptin in healthand disease

Interest in the regulation of body weight and the pathophysiology of obesit y has been rekindled by the cloning of the obese (ob) gene and identificati on of its product, leptin. Lepting impressive metabolic effects in mice (in hibition of food intake, stimulation of energy expenditure, reversal of obe sity, and amelioration of insulin resistance), though most desirable, are y et to be demonstrated in humans. However, numerous studies in humans indica te that leptin is a regulated hormone that may be involved in diverse physi ological and pathophysiological processes, The physiological factors that m odulate plasma leptin levels include sex, body fat, exercise, and fluctuati ons in caloric supply. Plasma leptin levels exhibit a peripubertal surge an d a postmenopausal decline, and they are responsive to hormonal manipulatio ns. Hormones that increase leptin production include insulin, glucocorticoi ds, estradiol, and growth hormone; those that decrease leptin levels includ e testosterone, somatostatin, and insulin-like growth factor I, End-stage r enal disease, a catabolic and anorectic state, is associated with marked el evation in plasma leptin levels. These and other data documenting the prese nce of leptin in placenta, cord blood, and breast milk and alterations in c ertain disease states are reviewed in this review focusing on leptin measur ement in humans. Understanding the role and regulation of leptin in health and disease is a prereguisite to a rational utilization of leptin-based reg imens in the treatment of disorders of human metabolism.