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SORCS1 and SORCS3 control energy balance and orexigenic peptide production

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Item Type:Article
Title:SORCS1 and SORCS3 control energy balance and orexigenic peptide production
Creators Name:Subkhangulova, A. and Malik, A.R. and Hermey, G. and Popp, O. and Dittmar, G. and Rathjen, T. and Poy, M.N. and Stumpf, A. and Beed, P.S. and Schmitz, D. and Breiderhoff, T. and Willnow, T.E.
Abstract:SORCS1 and SORCS3 are two related sorting receptors expressed in neurons of the arcuate nucleus of the hypothalamus. Using mouse models with individual or dual receptor deficiencies, we document a previously unknown function of these receptors in central control of metabolism. Specifically, SORCS1 and SORCS3 act as intracellular trafficking receptors for tropomyosin-related kinase B to attenuate signaling by brain-derived neurotrophic factor, a potent regulator of energy homeostasis. Loss of the joint action of SORCS1 and SORCS3 in mutant mice results in excessive production of the orexigenic neuropeptide agouti-related peptide and in a state of chronic energy excess characterized by enhanced food intake, decreased locomotor activity, diminished usage of lipids as metabolic fuel, and increased adiposity, albeit at overall reduced body weight. Our findings highlight a novel concept in regulation of the melanocortin system and the role played by trafficking receptors SORCS1 and SORCS3 in this process.
Keywords:Adiposity, Agouti-Related Peptide, Brain-Derived Neurotrophic Factor, TrkB, VPS10P Domain Receptors, Animals, Mice
Source:EMBO Reports
ISSN:1469-221X
Publisher:EMBO Press (U.K.)
Volume:19
Number:4
Page Range:e44810
Date:1 April 2018
Official Publication:https://doi.org/10.15252/embr.201744810
PubMed:View item in PubMed

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