Trib1 deficiency causes brown adipose respiratory chain depletion and mitochondrial disorder

Abstract Tribbles homolog 1 (TRIB1) belongs to the Tribbles family of pseudokinases, which plays a key role in tumorigenesis and inflammation. Although genome-wide analysis shows that TRIB1 expression is highly correlated with blood lipid levels, the relationship between TRIB1 and adipose tissue met...

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Autores principales:	Xuelian Zhang, Bin Zhang, Chenyang Zhang, Guibo Sun, Xiaobo Sun
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/7c3a574735e44118a747b838ecc600d8
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spelling	oai:doaj.org-article:7c3a574735e44118a747b838ecc600d82021-11-28T12:04:35ZTrib1 deficiency causes brown adipose respiratory chain depletion and mitochondrial disorder10.1038/s41419-021-04389-x2041-4889https://doaj.org/article/7c3a574735e44118a747b838ecc600d82021-11-01T00:00:00Zhttps://doi.org/10.1038/s41419-021-04389-xhttps://doaj.org/toc/2041-4889Abstract Tribbles homolog 1 (TRIB1) belongs to the Tribbles family of pseudokinases, which plays a key role in tumorigenesis and inflammation. Although genome-wide analysis shows that TRIB1 expression is highly correlated with blood lipid levels, the relationship between TRIB1 and adipose tissue metabolism remains unclear. Accordingly, the aim of the present study was to explore the role of TRIB1 on mitochondrial function in the brown adipose tissue (BAT). Trib1-knockout mice were established using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology. The metabolic function of the BAT was induced by a β3-adrenoceptor agonist and the energy metabolism function of mitochondria in the BAT of mice was evaluated. Trib1-knockout mice exhibited obesity and impaired BAT thermogenesis. In particular, Trib1 knockout reduced the ability of the BAT to maintain body temperature, inhibited β3-adrenoceptor agonist-induced thermogenesis, and accelerated lipid accumulation in the liver and adipose tissues. In addition, Trib1 knockout reduced mitochondrial respiratory chain complex III activity, produced an imbalance between mitochondrial fusion and fission, caused mitochondrial structural damage and dysfunction, and affected heat production and lipid metabolism in the BAT. Conversely, overexpression of Trib1 in 3T3-L1 adipocytes increased the number of mitochondria and improved respiratory function. These findings support the role of Trib1 in regulating the mitochondrial respiratory chain and mitochondrial dynamics by affecting mitochondrial function and thermogenesis in the BAT.Xuelian ZhangBin ZhangChenyang ZhangGuibo SunXiaobo SunNature Publishing GrouparticleCytologyQH573-671ENCell Death and Disease, Vol 12, Iss 12, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Xuelian Zhang Bin Zhang Chenyang Zhang Guibo Sun Xiaobo Sun Trib1 deficiency causes brown adipose respiratory chain depletion and mitochondrial disorder
description	Abstract Tribbles homolog 1 (TRIB1) belongs to the Tribbles family of pseudokinases, which plays a key role in tumorigenesis and inflammation. Although genome-wide analysis shows that TRIB1 expression is highly correlated with blood lipid levels, the relationship between TRIB1 and adipose tissue metabolism remains unclear. Accordingly, the aim of the present study was to explore the role of TRIB1 on mitochondrial function in the brown adipose tissue (BAT). Trib1-knockout mice were established using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology. The metabolic function of the BAT was induced by a β3-adrenoceptor agonist and the energy metabolism function of mitochondria in the BAT of mice was evaluated. Trib1-knockout mice exhibited obesity and impaired BAT thermogenesis. In particular, Trib1 knockout reduced the ability of the BAT to maintain body temperature, inhibited β3-adrenoceptor agonist-induced thermogenesis, and accelerated lipid accumulation in the liver and adipose tissues. In addition, Trib1 knockout reduced mitochondrial respiratory chain complex III activity, produced an imbalance between mitochondrial fusion and fission, caused mitochondrial structural damage and dysfunction, and affected heat production and lipid metabolism in the BAT. Conversely, overexpression of Trib1 in 3T3-L1 adipocytes increased the number of mitochondria and improved respiratory function. These findings support the role of Trib1 in regulating the mitochondrial respiratory chain and mitochondrial dynamics by affecting mitochondrial function and thermogenesis in the BAT.
format	article
author	Xuelian Zhang Bin Zhang Chenyang Zhang Guibo Sun Xiaobo Sun
author_facet	Xuelian Zhang Bin Zhang Chenyang Zhang Guibo Sun Xiaobo Sun
author_sort	Xuelian Zhang
title	Trib1 deficiency causes brown adipose respiratory chain depletion and mitochondrial disorder
title_short	Trib1 deficiency causes brown adipose respiratory chain depletion and mitochondrial disorder
title_full	Trib1 deficiency causes brown adipose respiratory chain depletion and mitochondrial disorder
title_fullStr	Trib1 deficiency causes brown adipose respiratory chain depletion and mitochondrial disorder
title_full_unstemmed	Trib1 deficiency causes brown adipose respiratory chain depletion and mitochondrial disorder
title_sort	trib1 deficiency causes brown adipose respiratory chain depletion and mitochondrial disorder
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/7c3a574735e44118a747b838ecc600d8
work_keys_str_mv	AT xuelianzhang trib1deficiencycausesbrownadiposerespiratorychaindepletionandmitochondrialdisorder AT binzhang trib1deficiencycausesbrownadiposerespiratorychaindepletionandmitochondrialdisorder AT chenyangzhang trib1deficiencycausesbrownadiposerespiratorychaindepletionandmitochondrialdisorder AT guibosun trib1deficiencycausesbrownadiposerespiratorychaindepletionandmitochondrialdisorder AT xiaobosun trib1deficiencycausesbrownadiposerespiratorychaindepletionandmitochondrialdisorder
_version_	1718408206892400640

Trib1 deficiency causes brown adipose respiratory chain depletion and mitochondrial disorder

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