Leptin in Leanness and Obesity

Highlights

• Leptin is an important regulator of neuroendocrine function and energy homeostasis, and blood levels of leptin reflect energy stores, fat mass, or energy deprivation.

• Treatment with leptin can be effective in patients with certain cardiometabolic diseases associated with leptin deficiency but not in common obesity.

• Additional physiological studies and clinical trials are needed to explore potential clinical applications of next-generation leptin analogs.

Abstract

Leptin has emerged over the past 2 decades as a key hormone secreted by adipose tissue that conveys information on energy stores. Leptin is considered an important regulator of both neuroendocrine function and energy homeostasis. Numerous studies (mainly preclinical and much less in humans) have investigated the mechanisms of leptin’s actions both in the healthy state as well as in a wide range of metabolic diseases. In this review, the authors present leptin physiology and review the main findings from animal studies, observational and interventional studies, and clinical trials in humans that have investigated the role of leptin in metabolism and cardiometabolic diseases (energy deficiency, obesity, diabetes, cardiovascular diseases, nonalcoholic fatty liver disease). The authors discuss the similarities and discrepancies between animal and human biology and present clinical applications of leptin, directions for future research, and current approaches for the development of the next-generation leptin analogs.