A brown fat-enriched adipokine Adissp controls adipose thermogenesis and glucose homeostasis
The signaling mechanisms underlying adipose thermogenesis have not been fully elucidated. Particularly, the involvement of adipokines that are selectively expressed in brown adipose tissue (BAT) and beige adipocytes remains to be investigated. Here we show that a previously uncharacterized adipokine...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9741603/ https://www.ncbi.nlm.nih.gov/pubmed/36496438 http://dx.doi.org/10.1038/s41467-022-35335-w |
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author | Chen, Qingbo Huang, Lei Pan, Dongning Hu, Kai Li, Rui Friedline, Randall H. Kim, Jason K. Zhu, Lihua Julie Guertin, David A. Wang, Yong-Xu |
author_facet | Chen, Qingbo Huang, Lei Pan, Dongning Hu, Kai Li, Rui Friedline, Randall H. Kim, Jason K. Zhu, Lihua Julie Guertin, David A. Wang, Yong-Xu |
author_sort | Chen, Qingbo |
collection | PubMed |
description | The signaling mechanisms underlying adipose thermogenesis have not been fully elucidated. Particularly, the involvement of adipokines that are selectively expressed in brown adipose tissue (BAT) and beige adipocytes remains to be investigated. Here we show that a previously uncharacterized adipokine (UPF0687 protein / human C20orf27 homolog) we named as Adissp (Adipose-secreted signaling protein) is a key regulator for white adipose tissue (WAT) thermogenesis and glucose homeostasis. Adissp expression is adipose-specific and highly BAT-enriched, and its secretion is stimulated by β3-adrenergic activation. Gain-of-functional studies collectively showed that secreted Adissp promotes WAT thermogenesis, improves glucose homeostasis, and protects against obesity. Adipose-specific Adissp knockout mice are defective in WAT browning, and are susceptible to high fat diet-induced obesity and hyperglycemia. Mechanistically, Adissp binds to a putative receptor on adipocyte surface and activates protein kinase A independently of β-adrenergic signaling. These results establish BAT-enriched Adissp as a major upstream signaling component in thermogenesis and offer a potential avenue for the treatment of obesity and diabetes. |
format | Online Article Text |
id | pubmed-9741603 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-97416032022-12-12 A brown fat-enriched adipokine Adissp controls adipose thermogenesis and glucose homeostasis Chen, Qingbo Huang, Lei Pan, Dongning Hu, Kai Li, Rui Friedline, Randall H. Kim, Jason K. Zhu, Lihua Julie Guertin, David A. Wang, Yong-Xu Nat Commun Article The signaling mechanisms underlying adipose thermogenesis have not been fully elucidated. Particularly, the involvement of adipokines that are selectively expressed in brown adipose tissue (BAT) and beige adipocytes remains to be investigated. Here we show that a previously uncharacterized adipokine (UPF0687 protein / human C20orf27 homolog) we named as Adissp (Adipose-secreted signaling protein) is a key regulator for white adipose tissue (WAT) thermogenesis and glucose homeostasis. Adissp expression is adipose-specific and highly BAT-enriched, and its secretion is stimulated by β3-adrenergic activation. Gain-of-functional studies collectively showed that secreted Adissp promotes WAT thermogenesis, improves glucose homeostasis, and protects against obesity. Adipose-specific Adissp knockout mice are defective in WAT browning, and are susceptible to high fat diet-induced obesity and hyperglycemia. Mechanistically, Adissp binds to a putative receptor on adipocyte surface and activates protein kinase A independently of β-adrenergic signaling. These results establish BAT-enriched Adissp as a major upstream signaling component in thermogenesis and offer a potential avenue for the treatment of obesity and diabetes. Nature Publishing Group UK 2022-12-10 /pmc/articles/PMC9741603/ /pubmed/36496438 http://dx.doi.org/10.1038/s41467-022-35335-w 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 Chen, Qingbo Huang, Lei Pan, Dongning Hu, Kai Li, Rui Friedline, Randall H. Kim, Jason K. Zhu, Lihua Julie Guertin, David A. Wang, Yong-Xu A brown fat-enriched adipokine Adissp controls adipose thermogenesis and glucose homeostasis |
title | A brown fat-enriched adipokine Adissp controls adipose thermogenesis and glucose homeostasis |
title_full | A brown fat-enriched adipokine Adissp controls adipose thermogenesis and glucose homeostasis |
title_fullStr | A brown fat-enriched adipokine Adissp controls adipose thermogenesis and glucose homeostasis |
title_full_unstemmed | A brown fat-enriched adipokine Adissp controls adipose thermogenesis and glucose homeostasis |
title_short | A brown fat-enriched adipokine Adissp controls adipose thermogenesis and glucose homeostasis |
title_sort | brown fat-enriched adipokine adissp controls adipose thermogenesis and glucose homeostasis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9741603/ https://www.ncbi.nlm.nih.gov/pubmed/36496438 http://dx.doi.org/10.1038/s41467-022-35335-w |
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