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Secreted EMC10 is upregulated in human obesity and its neutralizing antibody prevents diet-induced obesity in mice
Secreted isoform of endoplasmic reticulum membrane complex subunit 10 (scEMC10) is a poorly characterized secreted protein of largely unknown physiological function. Here we demonstrate that scEMC10 is upregulated in people with obesity and is positively associated with insulin resistance. Consisten...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9705309/ https://www.ncbi.nlm.nih.gov/pubmed/36443308 http://dx.doi.org/10.1038/s41467-022-34259-9 |
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author | Wang, Xuanchun Li, Yanliang Qiang, Guifen Wang, Kaihua Dai, Jiarong McCann, Maximilian Munoz, Marcos D. Gil, Victoria Yu, Yifei Li, Shengxian Yang, Zhihong Xu, Shanshan Cordoba-Chacon, Jose De Jesus, Dario F. Sun, Bei Chen, Kuangyang Wang, Yahao Liu, Xiaoxia Miao, Qing Zhou, Linuo Hu, Renming Ding, Qiang Kulkarni, Rohit N. Gao, Daming Blüher, Matthias Liew, Chong Wee |
author_facet | Wang, Xuanchun Li, Yanliang Qiang, Guifen Wang, Kaihua Dai, Jiarong McCann, Maximilian Munoz, Marcos D. Gil, Victoria Yu, Yifei Li, Shengxian Yang, Zhihong Xu, Shanshan Cordoba-Chacon, Jose De Jesus, Dario F. Sun, Bei Chen, Kuangyang Wang, Yahao Liu, Xiaoxia Miao, Qing Zhou, Linuo Hu, Renming Ding, Qiang Kulkarni, Rohit N. Gao, Daming Blüher, Matthias Liew, Chong Wee |
author_sort | Wang, Xuanchun |
collection | PubMed |
description | Secreted isoform of endoplasmic reticulum membrane complex subunit 10 (scEMC10) is a poorly characterized secreted protein of largely unknown physiological function. Here we demonstrate that scEMC10 is upregulated in people with obesity and is positively associated with insulin resistance. Consistent with a causal role for scEMC10 in obesity, Emc10(-/-) mice are resistant to diet-induced obesity due to an increase in energy expenditure, while scEMC10 overexpression decreases energy expenditure, thus promoting obesity in mouse. Furthermore, neutralization of circulating scEMC10 using a monoclonal antibody reduces body weight and enhances insulin sensitivity in obese mice. Mechanistically, we provide evidence that scEMC10 can be transported into cells where it binds to the catalytic subunit of PKA and inhibits its stimulatory action on CREB while ablation of EMC10 promotes thermogenesis in adipocytes via activation of the PKA signalling pathway and its downstream targets. Taken together, our data identify scEMC10 as a circulating inhibitor of thermogenesis and a potential therapeutic target for obesity and its cardiometabolic complications. |
format | Online Article Text |
id | pubmed-9705309 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-97053092022-11-30 Secreted EMC10 is upregulated in human obesity and its neutralizing antibody prevents diet-induced obesity in mice Wang, Xuanchun Li, Yanliang Qiang, Guifen Wang, Kaihua Dai, Jiarong McCann, Maximilian Munoz, Marcos D. Gil, Victoria Yu, Yifei Li, Shengxian Yang, Zhihong Xu, Shanshan Cordoba-Chacon, Jose De Jesus, Dario F. Sun, Bei Chen, Kuangyang Wang, Yahao Liu, Xiaoxia Miao, Qing Zhou, Linuo Hu, Renming Ding, Qiang Kulkarni, Rohit N. Gao, Daming Blüher, Matthias Liew, Chong Wee Nat Commun Article Secreted isoform of endoplasmic reticulum membrane complex subunit 10 (scEMC10) is a poorly characterized secreted protein of largely unknown physiological function. Here we demonstrate that scEMC10 is upregulated in people with obesity and is positively associated with insulin resistance. Consistent with a causal role for scEMC10 in obesity, Emc10(-/-) mice are resistant to diet-induced obesity due to an increase in energy expenditure, while scEMC10 overexpression decreases energy expenditure, thus promoting obesity in mouse. Furthermore, neutralization of circulating scEMC10 using a monoclonal antibody reduces body weight and enhances insulin sensitivity in obese mice. Mechanistically, we provide evidence that scEMC10 can be transported into cells where it binds to the catalytic subunit of PKA and inhibits its stimulatory action on CREB while ablation of EMC10 promotes thermogenesis in adipocytes via activation of the PKA signalling pathway and its downstream targets. Taken together, our data identify scEMC10 as a circulating inhibitor of thermogenesis and a potential therapeutic target for obesity and its cardiometabolic complications. Nature Publishing Group UK 2022-11-28 /pmc/articles/PMC9705309/ /pubmed/36443308 http://dx.doi.org/10.1038/s41467-022-34259-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Wang, Xuanchun Li, Yanliang Qiang, Guifen Wang, Kaihua Dai, Jiarong McCann, Maximilian Munoz, Marcos D. Gil, Victoria Yu, Yifei Li, Shengxian Yang, Zhihong Xu, Shanshan Cordoba-Chacon, Jose De Jesus, Dario F. Sun, Bei Chen, Kuangyang Wang, Yahao Liu, Xiaoxia Miao, Qing Zhou, Linuo Hu, Renming Ding, Qiang Kulkarni, Rohit N. Gao, Daming Blüher, Matthias Liew, Chong Wee Secreted EMC10 is upregulated in human obesity and its neutralizing antibody prevents diet-induced obesity in mice |
title | Secreted EMC10 is upregulated in human obesity and its neutralizing antibody prevents diet-induced obesity in mice |
title_full | Secreted EMC10 is upregulated in human obesity and its neutralizing antibody prevents diet-induced obesity in mice |
title_fullStr | Secreted EMC10 is upregulated in human obesity and its neutralizing antibody prevents diet-induced obesity in mice |
title_full_unstemmed | Secreted EMC10 is upregulated in human obesity and its neutralizing antibody prevents diet-induced obesity in mice |
title_short | Secreted EMC10 is upregulated in human obesity and its neutralizing antibody prevents diet-induced obesity in mice |
title_sort | secreted emc10 is upregulated in human obesity and its neutralizing antibody prevents diet-induced obesity in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9705309/ https://www.ncbi.nlm.nih.gov/pubmed/36443308 http://dx.doi.org/10.1038/s41467-022-34259-9 |
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