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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number7658
JournalScientific reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

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Connexin 43
Brown Adipose Tissue
Maintenance
Adipocytes
Autophagy
High Fat Diet
Mitochondria
White Adipose Tissue
Adrenergic Agonists
Immunoblotting
Knockout Mice
Adrenergic Agents
Adrenergic Receptors
Reactive Oxygen Species
Electron Microscopy
Immunohistochemistry
Insulin

All Science Journal Classification (ASJC) codes

  • General

Cite this

Kim, S. N., Kwon, H. J., Im, S. W., Son, Y. H., Akindehin, S., Jung, Y. S., ... Lee, Y. H. (2017). Connexin 43 is required for the maintenance of mitochondrial integrity in brown adipose tissue. Scientific reports, 7(1), [7658]. https://doi.org/10.1038/s41598-017-07658-y
Kim, Sang Nam ; Kwon, Hyun Jung ; Im, Seo Woo ; Son, Yeon Ho ; Akindehin, Seun ; Jung, Young Suk ; Lee, Se Jeong ; Rhyu, Im Joo ; Kim, Il Yong ; Seong, Je Kyoung ; Lee, Jinu ; Yoo, Hee Chan ; Granneman, James G. ; Lee, Yun Hee. / Connexin 43 is required for the maintenance of mitochondrial integrity in brown adipose tissue. In: Scientific reports. 2017 ; Vol. 7, No. 1.
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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.",
author = "Kim, {Sang Nam} and Kwon, {Hyun Jung} and Im, {Seo Woo} and Son, {Yeon Ho} and Seun Akindehin and Jung, {Young Suk} and Lee, {Se Jeong} and Rhyu, {Im Joo} and Kim, {Il Yong} and Seong, {Je Kyoung} and Jinu Lee and Yoo, {Hee Chan} and Granneman, {James G.} and Lee, {Yun Hee}",
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Kim, SN, Kwon, HJ, Im, SW, Son, YH, Akindehin, S, Jung, YS, Lee, SJ, Rhyu, IJ, Kim, IY, Seong, JK, Lee, J, Yoo, HC, Granneman, JG & Lee, YH 2017, 'Connexin 43 is required for the maintenance of mitochondrial integrity in brown adipose tissue', Scientific reports, vol. 7, no. 1, 7658. https://doi.org/10.1038/s41598-017-07658-y

Connexin 43 is required for the maintenance of mitochondrial integrity in brown adipose tissue. / Kim, Sang Nam; Kwon, Hyun Jung; Im, Seo Woo; Son, Yeon Ho; Akindehin, Seun; Jung, Young Suk; Lee, Se Jeong; Rhyu, Im Joo; Kim, Il Yong; Seong, Je Kyoung; Lee, Jinu; Yoo, Hee Chan; Granneman, James G.; Lee, Yun Hee.

In: Scientific reports, Vol. 7, No. 1, 7658, 01.12.2017.

Research output: Contribution to journalArticle

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AU - Kim, Sang Nam

AU - Kwon, Hyun Jung

AU - Im, Seo Woo

AU - Son, Yeon Ho

AU - Akindehin, Seun

AU - Jung, Young Suk

AU - Lee, Se Jeong

AU - Rhyu, Im Joo

AU - Kim, Il Yong

AU - Seong, Je Kyoung

AU - Lee, Jinu

AU - Yoo, Hee Chan

AU - Granneman, James G.

AU - Lee, Yun Hee

PY - 2017/12/1

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N2 - 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.

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