Cargando…
SORCS1 and SORCS3 control energy balance and orexigenic peptide production
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 a...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891432/ https://www.ncbi.nlm.nih.gov/pubmed/29440124 http://dx.doi.org/10.15252/embr.201744810 |
_version_ | 1783313005053739008 |
---|---|
author | 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 |
author_facet | 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 |
author_sort | Subkhangulova, Aygul |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5891432 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-58914322018-04-13 SORCS1 and SORCS3 control energy balance and orexigenic peptide production 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 EMBO Rep Articles 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. John Wiley and Sons Inc. 2018-02-12 2018-04 /pmc/articles/PMC5891432/ /pubmed/29440124 http://dx.doi.org/10.15252/embr.201744810 Text en © 2018 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles 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 SORCS1 and SORCS3 control energy balance and orexigenic peptide production |
title |
SORCS1 and SORCS3 control energy balance and orexigenic peptide production |
title_full |
SORCS1 and SORCS3 control energy balance and orexigenic peptide production |
title_fullStr |
SORCS1 and SORCS3 control energy balance and orexigenic peptide production |
title_full_unstemmed |
SORCS1 and SORCS3 control energy balance and orexigenic peptide production |
title_short |
SORCS1 and SORCS3 control energy balance and orexigenic peptide production |
title_sort | sorcs1 and sorcs3 control energy balance and orexigenic peptide production |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891432/ https://www.ncbi.nlm.nih.gov/pubmed/29440124 http://dx.doi.org/10.15252/embr.201744810 |
work_keys_str_mv | AT subkhangulovaaygul sorcs1andsorcs3controlenergybalanceandorexigenicpeptideproduction AT malikannar sorcs1andsorcs3controlenergybalanceandorexigenicpeptideproduction AT hermeyguido sorcs1andsorcs3controlenergybalanceandorexigenicpeptideproduction AT poppoliver sorcs1andsorcs3controlenergybalanceandorexigenicpeptideproduction AT dittmargunnar sorcs1andsorcs3controlenergybalanceandorexigenicpeptideproduction AT rathjenthomas sorcs1andsorcs3controlenergybalanceandorexigenicpeptideproduction AT poymatthewn sorcs1andsorcs3controlenergybalanceandorexigenicpeptideproduction AT stumpfalexander sorcs1andsorcs3controlenergybalanceandorexigenicpeptideproduction AT beedprateepsanker sorcs1andsorcs3controlenergybalanceandorexigenicpeptideproduction AT schmitzdietmar sorcs1andsorcs3controlenergybalanceandorexigenicpeptideproduction AT breiderhofftilman sorcs1andsorcs3controlenergybalanceandorexigenicpeptideproduction AT willnowthomase sorcs1andsorcs3controlenergybalanceandorexigenicpeptideproduction |