Open Access
Leptin receptor signaling: pathways to leptin resistance
Joris Wauman1,Jan Tavernier1
Department of Medical Protein Research, Flanders Interuniversity Institute for Biotechnology (VIB), Ghent University, Albert Baertsoenkaai 3, B-9000 Ghent, Belgium
DOI: 10.2741/3885 Volume 16 Issue 7, pp.2771-2793
Published: 01 June 2011
(This article belongs to the Special Issue Regulation of signalling in health and disease)

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.

Share and Cite
Joris Wauman, Jan Tavernier. Leptin receptor signaling: pathways to leptin resistance. Frontiers in Bioscience-Landmark. 2011. 16(7); 2771-2793.