Purpose of review
This article summarizes recent clinical investigations involving leptin administration in a variety of human disease states and presents new information regarding the role of leptin in the neuroendocrine control of energy homeostasis, reproduction, and immune function in humans.
Accumulating data from basic science laboratories as well as observational studies in humans have led to hypotheses and recent proof-of-concept clinical trials successfully exploring the role of leptin in several disease states characterized by leptin deficiency. These leptin deficiency states include states of absolute leptin deficiency, due to inactivating mutations of the leptin gene, or states of relative leptin deficiency and hypoleptinemia accompanying negative energy balance in subjects with anorexia nervosa or hypothalamic amenorrhea and generalized lipoatrophy, either congenital or acquired in the context of the highly active antiretroviral therapy-induced metabolic syndrome. Leptin treatment, in replacement doses, normalizes neuroendocrine, metabolic, and immune function in leptin deficiency states and may prove of therapeutic significance.
Recent proof-of-concept studies involving leptin administration to humans with leptin deficiency support its critical role in regulating energy homeostasis, neuroendocrine and immune function, and insulin resistance and serve as the foundation for future clinical trials involving leptin administration to prove its potential role in the treatment of several disease states, including hypothalamic amenorrhea, inflammation (immune dysfunction), metabolism, and insulin resistance (diabetes).