CHAPTER 3

One Receptor for Multiple Pathways: Focus on Leptin Signaling

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RODOLFO GOMEZ, JAVIER CONDE, MORENA SCOTECE AND ORESTE GUALILLO*

Sergas (Servizo Galego de Saude), Research Laboratory 9 (NEIRID LAB: Neuroendocrine Interactions in Rheumatology and Inflammatory Disease), Institute of Medical Research (IDIS), Santiago University Clinical Hospital, Santiago de Compostela, 15706, Spain

3.1 Leptin

Leptin is a 16-kDa non-glycosylated polypeptide hormone encoded by the gene obese (ob), the murine homolog of the human gene LEP. From a structural viewpoint, leptin belongs to the type I cytokine superfamily with a four alpha helical bundle motif. It shares 84% homology between humans and mice.1 It is mainly produced by adipocytes.1,2 Although other cells or tissues produce leptin in a significant way, visceral and subcutaneous fat are responsible for more than 80% of total leptin production.3,4 Circulating leptin levels are modulated by several factors such as food intake, sex, hormones and cytokines; however, leptin levels are directly proportional to the white adipose tissue (WAT) mass. Likewise, they are negatively correlated with glucocorticoid levels.5–9

RSC Drug Discovery Series No. 10 Extracellular and Intracellular Signaling

Edited by James D. Adams, Jr. and Keith K. Parker r Royal Society of Chemistry 2011

Published by the Royal Society of Chemistry, www.rsc.org

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