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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
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
_version_ 1784848360164818944
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
work_keys_str_mv AT chenqingbo abrownfatenrichedadipokineadisspcontrolsadiposethermogenesisandglucosehomeostasis
AT huanglei abrownfatenrichedadipokineadisspcontrolsadiposethermogenesisandglucosehomeostasis
AT pandongning abrownfatenrichedadipokineadisspcontrolsadiposethermogenesisandglucosehomeostasis
AT hukai abrownfatenrichedadipokineadisspcontrolsadiposethermogenesisandglucosehomeostasis
AT lirui abrownfatenrichedadipokineadisspcontrolsadiposethermogenesisandglucosehomeostasis
AT friedlinerandallh abrownfatenrichedadipokineadisspcontrolsadiposethermogenesisandglucosehomeostasis
AT kimjasonk abrownfatenrichedadipokineadisspcontrolsadiposethermogenesisandglucosehomeostasis
AT zhulihuajulie abrownfatenrichedadipokineadisspcontrolsadiposethermogenesisandglucosehomeostasis
AT guertindavida abrownfatenrichedadipokineadisspcontrolsadiposethermogenesisandglucosehomeostasis
AT wangyongxu abrownfatenrichedadipokineadisspcontrolsadiposethermogenesisandglucosehomeostasis
AT chenqingbo brownfatenrichedadipokineadisspcontrolsadiposethermogenesisandglucosehomeostasis
AT huanglei brownfatenrichedadipokineadisspcontrolsadiposethermogenesisandglucosehomeostasis
AT pandongning brownfatenrichedadipokineadisspcontrolsadiposethermogenesisandglucosehomeostasis
AT hukai brownfatenrichedadipokineadisspcontrolsadiposethermogenesisandglucosehomeostasis
AT lirui brownfatenrichedadipokineadisspcontrolsadiposethermogenesisandglucosehomeostasis
AT friedlinerandallh brownfatenrichedadipokineadisspcontrolsadiposethermogenesisandglucosehomeostasis
AT kimjasonk brownfatenrichedadipokineadisspcontrolsadiposethermogenesisandglucosehomeostasis
AT zhulihuajulie brownfatenrichedadipokineadisspcontrolsadiposethermogenesisandglucosehomeostasis
AT guertindavida brownfatenrichedadipokineadisspcontrolsadiposethermogenesisandglucosehomeostasis
AT wangyongxu brownfatenrichedadipokineadisspcontrolsadiposethermogenesisandglucosehomeostasis