Connexin 43 is required for the maintenance of mitochondrial integrity in brown adipose tissue

Abstract We investigated the role of connexin 43 (Cx43) in maintaining the integrity of mitochondria in brown adipose tissue (BAT). The functional effects of Cx43 were evaluated using inducible, adipocyte-specific Cx43 knockout in mice (Gja1 adipoq KO) and by overexpression and knockdown of Cx43 in...

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Autores principales:	Sang-Nam Kim, Hyun-Jung Kwon, Seo-Woo Im, Yeon-Ho Son, Seun Akindehin, Young-Suk Jung, Se Jeong Lee, Im Joo Rhyu, Il Yong Kim, Je-Kyoung Seong, Jinu Lee, Hee-Chan Yoo, James G. Granneman, Yun-Hee Lee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/447d2147654f468aa1f2190154e48614
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spelling	oai:doaj.org-article:447d2147654f468aa1f2190154e486142021-12-02T15:05:00ZConnexin 43 is required for the maintenance of mitochondrial integrity in brown adipose tissue10.1038/s41598-017-07658-y2045-2322https://doaj.org/article/447d2147654f468aa1f2190154e486142017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07658-yhttps://doaj.org/toc/2045-2322Abstract We investigated the role of connexin 43 (Cx43) in maintaining the integrity of mitochondria in brown adipose tissue (BAT). The functional effects of Cx43 were evaluated using inducible, adipocyte-specific Cx43 knockout in mice (Gja1 adipoq KO) and by overexpression and knockdown of Cx43 in cultured adipocytes. Mitochondrial morphology was evaluated by electron microscopy and mitochondrial function and autophagy were assessed by immunoblotting, immunohistochemistry, and qPCR. The metabolic effects of adipocyte-specific knockout of Cx43 were assessed during cold stress and following high fat diet feeding. Cx43 expression was higher in BAT compared to white adipose tissue. Treatment with the β3-adrenergic receptor agonist CL316,243 increased Cx43 expression and mitochondrial localization. Gja1 adipoq KO mice reduced mitochondrial density and increased the presence of damaged mitochondria in BAT. Moreover, metabolic activation with CL316,243 further reduced mitochondrial integrity and upregulated autophagy in the BAT of Gja1 adipoq KO mice. Inhibition of Cx43 in cultured adipocytes increased the generation of reactive oxygen species and induction of autophagy during β-adrenergic stimulation. Gja1 adipoq KO mice were cold intolerant, expended less energy in response to β3-adrenergic receptor activation, and were more insulin resistant after a high-fat diet challenge. Collectively, our data demonstrate that Cx43 is required for maintaining the mitochondrial integrity and metabolic activity of BAT.Sang-Nam KimHyun-Jung KwonSeo-Woo ImYeon-Ho SonSeun AkindehinYoung-Suk JungSe Jeong LeeIm Joo RhyuIl Yong KimJe-Kyoung SeongJinu LeeHee-Chan YooJames G. GrannemanYun-Hee LeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sang-Nam Kim Hyun-Jung Kwon Seo-Woo Im Yeon-Ho Son Seun Akindehin Young-Suk Jung Se Jeong Lee Im Joo Rhyu Il Yong Kim Je-Kyoung Seong Jinu Lee Hee-Chan Yoo James G. Granneman Yun-Hee Lee Connexin 43 is required for the maintenance of mitochondrial integrity in brown adipose tissue
description	Abstract We investigated the role of connexin 43 (Cx43) in maintaining the integrity of mitochondria in brown adipose tissue (BAT). The functional effects of Cx43 were evaluated using inducible, adipocyte-specific Cx43 knockout in mice (Gja1 adipoq KO) and by overexpression and knockdown of Cx43 in cultured adipocytes. Mitochondrial morphology was evaluated by electron microscopy and mitochondrial function and autophagy were assessed by immunoblotting, immunohistochemistry, and qPCR. The metabolic effects of adipocyte-specific knockout of Cx43 were assessed during cold stress and following high fat diet feeding. Cx43 expression was higher in BAT compared to white adipose tissue. Treatment with the β3-adrenergic receptor agonist CL316,243 increased Cx43 expression and mitochondrial localization. Gja1 adipoq KO mice reduced mitochondrial density and increased the presence of damaged mitochondria in BAT. Moreover, metabolic activation with CL316,243 further reduced mitochondrial integrity and upregulated autophagy in the BAT of Gja1 adipoq KO mice. Inhibition of Cx43 in cultured adipocytes increased the generation of reactive oxygen species and induction of autophagy during β-adrenergic stimulation. Gja1 adipoq KO mice were cold intolerant, expended less energy in response to β3-adrenergic receptor activation, and were more insulin resistant after a high-fat diet challenge. Collectively, our data demonstrate that Cx43 is required for maintaining the mitochondrial integrity and metabolic activity of BAT.
format	article
author	Sang-Nam Kim Hyun-Jung Kwon Seo-Woo Im Yeon-Ho Son Seun Akindehin Young-Suk Jung Se Jeong Lee Im Joo Rhyu Il Yong Kim Je-Kyoung Seong Jinu Lee Hee-Chan Yoo James G. Granneman Yun-Hee Lee
author_facet	Sang-Nam Kim Hyun-Jung Kwon Seo-Woo Im Yeon-Ho Son Seun Akindehin Young-Suk Jung Se Jeong Lee Im Joo Rhyu Il Yong Kim Je-Kyoung Seong Jinu Lee Hee-Chan Yoo James G. Granneman Yun-Hee Lee
author_sort	Sang-Nam Kim
title	Connexin 43 is required for the maintenance of mitochondrial integrity in brown adipose tissue
title_short	Connexin 43 is required for the maintenance of mitochondrial integrity in brown adipose tissue
title_full	Connexin 43 is required for the maintenance of mitochondrial integrity in brown adipose tissue
title_fullStr	Connexin 43 is required for the maintenance of mitochondrial integrity in brown adipose tissue
title_full_unstemmed	Connexin 43 is required for the maintenance of mitochondrial integrity in brown adipose tissue
title_sort	connexin 43 is required for the maintenance of mitochondrial integrity in brown adipose tissue
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/447d2147654f468aa1f2190154e48614
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Connexin 43 is required for the maintenance of mitochondrial integrity in brown adipose tissue

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