Endocrine Abstracts

Leptin, a 167 aminoacid protein product of the ob gene, is an adipocyte-derived hormone that acts as a major regulator for food intake and energy homeostasis. Leptin is expressed mainly in white adipose tissue, but also in stomach and placenta. Leptin circulates in the serum in a free form or bound to leptin-binding proteins. Since its discovery, our understanding of leptin’s biological functions has expanded from antiobesity to broad effects on reproduction, hematopoiesis, angiogenesis, blood pressure, bone mass, lymphoid organ homeostasis, and T lymphocyte systems. Leptin orchestrates complex biological effects through its receptors, expressed both centrally and peripherally. Leptin deficiency or resistance can result in profound obesity, diabetes, and infertility in humans.

Leptin concentrations correlate linearly with increasing amounts of fat mass. Although the amount of fat is an important determinant of leptin concentrations, other factors are also relevant, including sex, adipose tissue-specific factors/site, hormones and cytokines. Importantly, women have higher leptin concentrations than men even after adjusting for body-mass index, which may be due to differential body-fat distribution or the effects of sex steroids. However, it has been realised that leptin might be more important at the other end of the energy homoeostasis spectrum — energy deprivation rather than obesity. Studies in animals and human beings have shown that low concentrations of leptin are fully or partly responsible for starvation-induced changes in neuroendocrine axes including low reproductive, thyroid, and insulin-like growth factor (IGF) hormones and such as exercise-induced amenorrhoea, non-athletic forms of hypothalamic amenorrhoea, and anorexia nervosa. Interestingly, clinical studies have shown that leptin and its receptors exhibit diurnal variation, are influenced by growth hormone status, and are influenced by insulin and glucocorticoids. These findings support the hypothesis that leptin expands function.