A heliocentric view of leptin

Leptin is significantly broadening our understanding of the mechanisms underlying neuroendocrine function. Initially, based on a rather static view of the hormone, most investigations focused on the effects of leptin on food intake control and body-weight homeostasis, with attention primarily focused on the implications of leptin as a lipostatic factor and central satiety agent. However, the almost ubiquitous distribution of leptin receptors in peripheral tissues provided a fertile area for investigation and a more dynamic view of leptin started to unfold. This adipocyte-derived circulating peptidic hormone, with a tertiary structure resembling that of members of the long-chain helical cytokine family, has generated an enormous interest in the interaction as well as integration between brain targets and peripheral signals. Considerable evidence for systemic effects of leptin on specific tissues and metabolic pathways indicates that leptin operates both directly and indirectly to orchestrate complex pathophysiological processes. Disentangling the biochemical and molecular mechanisms in which leptin is involved represents one of the major challenges ahead.