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 (Gja1adipoqKO) 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. Gja1adipoqKO 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 Gja1adipoqKO mice. Inhibition of Cx43 in cultured adipocytes increased the generation of reactive oxygen species and induction of autophagy during β-adrenergic stimulation. Gja1adipoqKO 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.

Details

Title
Connexin 43 is required for the maintenance of mitochondrial integrity in brown adipose tissue
Author
Sang-Nam, Kim 1 ; Hyun-Jung, Kwon 1 ; Seo-Woo Im 1 ; Yeon-Ho Son 1 ; Akindehin, Seun 1 ; Young-Suk, Jung 2 ; Se Jeong Lee 3 ; Im, Joo Rhyu 3 ; Il Yong Kim 4 ; Je-Kyoung Seong 4 ; Lee, Jinu 1 ; Hee-Chan, Yoo 1 ; Granneman, James G 5 ; Yun-Hee, Lee 1   VIAFID ORCID Logo 

 College of Pharmacy, Yonsei University, Incheon, South Korea 
 College of Pharmacy, Pusan National University, Busan, South Korea 
 Department of Anatomy, Korea University College of Medicine, Seoul, South Korea 
 Laboratory of Developmental Biology and Genomics, College of Veterinary Medicine, Seoul National University, Korea Mouse Phenotyping Center (KMPC), Seoul, South Korea 
 Center for Integrative Metabolic and Endocrine Research, Wayne State University School of Medicine, Detroit, MI, USA 
Pages
1-12
Publication year
2017
Publication date
Aug 2017
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1954582095
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.