Leptin receptor signaling: pathways to leptin resistance

Citations Over TimeTop 10% of 2011 papers

Abstract

The identification of spontaneous mutations in the leptin- and leptin receptor (ObR)-encoding ob and db gene, respectively, opened up a new field in obesity research. Leptin, an adipocyte-derived hormone, mirrors the body's fat stores and thereby informs the brain about the body's energy status. In the hypothalamus, leptin triggers specific neuronal subpopulations, like POMC and AgRP/NPY neurons, and activates several intracellular signaling events, including the JAK/STAT, MAPK, PI3K and mTOR pathway, which eventually translates into decreased food intake and increased energy expenditure. Leptin is also involved in the regulation of other physiological processes including reproduction, bone homeostasis and immune function. Here, we review the pathways that are activated upon ObR activation, how ObR expression is controlled and the molecular mechanisms leading to leptin resistance, i.e. the inability to adequately respond to elevated leptin levels and therefore a primary risk factor for obesity.

Related Papers

• → Leptin and leptin receptor: Analysis of a structure to function relationship in interaction and evolution from humans to fish(2012)90 cited
• → Normal Leptin Expression, Lower Adipogenic Ability, Decreased Leptin Receptor and Hyposensitivity to Leptin in Adolescent Idiopathic Scoliosis(2012)35 cited
• → Phenotypic Consequences of a Nonsense Mutation in the Leptin Receptor Gene (fak) in Obese Spontaneously Hypertensive Koletsky Rats (SHROB)(1998)55 cited
• → In vivo and in vitro evidence for a hepatic modulation of the leptin signal in rats(2004)21 cited
• → Mapping leptin's link to reproduction(2012)4 cited