title: Leptin: From structural insights to the design of antagonists.
abstract: After its discovery in 1994, it soon became clear that leptin acts as an adipocyte-derived hormone with a central role in the control of body weight and energy homeostasis. However, a growing body of evidence has revealed that leptin is a pleiotropic cytokine with activities on many peripheral cell types. Inappropriate leptin signaling can promote autoimmunity, certain cardiovascular diseases, elevated blood pressure and cancer, which makes leptin and the leptin receptor interesting targets for antagonism. Profound insights in the leptin receptor (LR) activation mechanisms are a prerequisite for the rational design of these antagonists. In this review, we focus on the molecular mechanisms underlying leptin receptor activation and signaling. We also discuss the current strategies to interfere with leptin signaling and their therapeutic potential.
authors.affiliation: Flanders Institute for Biotechnology (VIB), Department of Medical Protein Research, Faculty of Medicine and Health Sciences, Ghent University, A. Baertsoenkaai 3, 9000 Ghent, Belgium.
authors.forename: Lennart
authors.initials: L
authors.lastname: Zabeau
authors.affiliation: Flanders Institute for Biotechnology (VIB), Department of Medical Protein Research, Faculty of Medicine and Health Sciences, Ghent University, A. Baertsoenkaai 3, 9000 Ghent, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Peelman
authors.affiliation: Flanders Institute for Biotechnology (VIB), Department of Medical Protein Research, Faculty of Medicine and Health Sciences, Ghent University, A. Baertsoenkaai 3, 9000 Ghent, Belgium. Electronic address: jan.tavernier@vib-ugent.be.
authors.forename: Jan
authors.initials: J
authors.lastname: Tavernier
mesh_terms: D006801:Humans; D020738:Leptin / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D054411:Receptors, Leptin / Q000037:antagonists & inhibitors*; D015398:Signal Transduction
chemical_list: D020738:Leptin; D054411:Receptors, Leptin
keywords: antagonism; leptin; leptin receptor; modeling; structure