The discovery of
leptin was intrinsically associated with its ability to regulate
body weight. However, the effects of
leptin are more far-reaching and include profound
glucose-lowering and anti-lipogenic effects, independent of
leptin's regulation of
body weight. Regulation of
glucose metabolism by
leptin is mediated both centrally and via peripheral tissues and is influenced by the activation status of
insulin signaling pathways. Ectopic fat accumulation is diminished by both central and peripheral
leptin, an effect that is beneficial in
obesity-associated disorders. The magnitude of
leptin action depends upon the tissue, sex, and context being examined. Peripheral tissues that are of particular relevance include the endocrine pancreas, liver, skeletal muscle, adipose tissues, immune cells, and the cardiovascular system. As a result of its potent metabolic activity,
leptin is used to control
hyperglycemia in patients with
lipodystrophy and is being explored as an adjunct to
insulin in patients with
type 1 diabetes. To fully understand the role of
leptin in physiology and to maximize its therapeutic potential, the mechanisms of
leptin action in these tissues needs to be further explored.