Human Leptin: An Adipocyte Hormone with Weight-Regulatory and Endocrine Functions

Abstract

Leptin is synthesized and secreted primarily by adipocytes, and is present in serum in direct proportion to the amount of adipose tissue. The primary role of leptin is to provide to the central nervous system a signal of energy intake and energy stores in the body so that the hypothalamus can efficiently maintain a stable body weight. The receptor for leptin in the hypothalamus signals by activation of an associated janus kinase which phosphorylates signal transducer and activator of transcription (STAT) proteins that regulate neuronal gene expression. Genetic mutations in leptin and its receptor can result in obesity in both rodents and humans, supporting a central role for leptin in the regulation of body weight. Leptin has also been implicated in a variety of physiological processes other than body weight homeostasis. Many of these functions are mediated through the central nervous system; however, the presence of leptin receptors in tissues throughout the body suggests that leptin can also have direct effects on cells and tissues. Serum leptin levels have been associated with cardiovascular risk factors after correction for adiposity. Leptin can promote platelet aggregation, which requires expression of functional leptin receptors on the platelet. Leptin-induced increases in sympathetic nerve activity have been suggested to contribute to hypertension, and leptin has been observed to increase oxidative stress in cultured endothelial cells. Many of these pathophysiologic effects of leptin on the vasculature are most likely of importance when leptin levels are elevated in obese subjects due to resistance to the weight-reducing effects of the hormone. An improved understanding of the effects of leptin on the vasculature will provide valuable insight into the relationship between obesity and cardiovascular disease.