The groundbreaking discovery of leptin in 1994 ignited the field of obesity research by providing the first direct evidence for a hormonal system primarily involved in body weight regulation. Advances in this field over the past 15 years have led to a detailed understanding of the central targets and mechanisms of leptin action. Although the arcuate melanocortin pathway is currently the best described target of leptin action, in this article we review recent evidence pointing to a system in which leptin acts at distinct sites and through different mechanisms within the central nervous system (CNS) to mediate energy homeostasis and feeding behavior. It appears that leptin controls feeding not just by providing physiological satiety signal, but also by mediating “synaptic plasticity” as well as modulating the perception of reward associated with feeding. Furthermore, we also review advances in our understanding of leptin resistance, a critical consequence and possible precursor of obesity.
wal A, Yeo G. Leptin and the Control of Body Weight: A Review of Its Diverse Central Targets, Signaling Mechanisms, and Role in the Pathogenesis of Obesity Obesity 2010 February Metabolic Research Labs, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.