Leptin at 20: an overview

Historically, adipose tissue was considered to be a passive storage vessel discharging nutrients in times of famine and accumulating fat in times of surfeit. This view changed with the identification of leptin as an adipocyte hormone. Leptin functions as an afferent signal in a negative feedback loop that regulates food intake and metabolism to maintain homeostatic control of adipose tissue mass. Before this, the existence of a system maintaining homeostatic control of energy balance was unclear. The identification of leptin has thus uncovered a new endocrine system that also links changes in nutrition to adaptive responses in most if not all other physiologic systems. Further studies have revealed a set of clinical syndromes caused by leptin deficiency, including lipodystrophy and hypothalamic amenorrhea. This work has led to new therapeutic approaches for a number of human conditions and has also established a conceptual framework for studying the pathogenesis of obesity.