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SORCS 1 and SORCS 3 control energy balance and orexigenic peptide production
Author(s) -
Subkhangulova Aygul,
Malik Anna R,
Hermey Guido,
Popp Oliver,
Dittmar Gunnar,
Rathjen Thomas,
Poy Matthew N,
Stumpf Alexander,
Beed Prateep Sanker,
Schmitz Dietmar,
Breiderhoff Tilman,
Willnow Thomas E
Publication year - 2018
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201744810
Subject(s) - orexigenic , peptide , chemistry , microbiology and biotechnology , food science , biochemistry , biology , neuropeptide , receptor , neuropeptide y receptor
SORCS 1 and SORCS 3 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.