ADH5-mediated NO bioactivity maintains metabolic homeostasis in brown adipose tissue

Summary: Brown adipose tissue (BAT) thermogenic activity is tightly regulated by cellular redox status, but the underlying molecular mechanisms are incompletely understood. Protein S-nitrosylation, the nitric-oxide-mediated cysteine thiol protein modification, plays important roles in cellular redox...

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Autores principales:	Sara C. Sebag, Zeyuan Zhang, Qingwen Qian, Mark Li, Zhiyong Zhu, Mikako Harata, Wenxian Li, Leonid V. Zingman, Limin Liu, Vitor A. Lira, Matthew J. Potthoff, Alexander Bartelt, Ling Yang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	alcohol dehydrogenase 5 ADH5 brown adipose tissue BAT heat shock factor 1 HSF1 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/fa993ffe513b402bb490e9e9850283d2
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spelling	oai:doaj.org-article:fa993ffe513b402bb490e9e9850283d22021-11-18T04:47:51ZADH5-mediated NO bioactivity maintains metabolic homeostasis in brown adipose tissue2211-124710.1016/j.celrep.2021.110003https://doaj.org/article/fa993ffe513b402bb490e9e9850283d22021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211124721014819https://doaj.org/toc/2211-1247Summary: Brown adipose tissue (BAT) thermogenic activity is tightly regulated by cellular redox status, but the underlying molecular mechanisms are incompletely understood. Protein S-nitrosylation, the nitric-oxide-mediated cysteine thiol protein modification, plays important roles in cellular redox regulation. Here we show that diet-induced obesity (DIO) and acute cold exposure elevate BAT protein S-nitrosylation, including UCP1. This thermogenic-induced nitric oxide bioactivity is regulated by S-nitrosoglutathione reductase (GSNOR; alcohol dehydrogenase 5 [ADH5]), a denitrosylase that balances the intracellular nitroso-redox status. Loss of ADH5 in BAT impairs cold-induced UCP1-dependent thermogenesis and worsens obesity-associated metabolic dysfunction. Mechanistically, we demonstrate that Adh5 expression is induced by the transcription factor heat shock factor 1 (HSF1), and administration of an HSF1 activator to BAT of DIO mice increases Adh5 expression and significantly improves UCP1-mediated respiration. Together, these data indicate that ADH5 controls BAT nitroso-redox homeostasis to regulate adipose thermogenesis, which may be therapeutically targeted to improve metabolic health.Sara C. SebagZeyuan ZhangQingwen QianMark LiZhiyong ZhuMikako HarataWenxian LiLeonid V. ZingmanLimin LiuVitor A. LiraMatthew J. PotthoffAlexander BarteltLing YangElsevierarticlealcohol dehydrogenase 5ADH5brown adipose tissueBATheat shock factor 1HSF1Biology (General)QH301-705.5ENCell Reports, Vol 37, Iss 7, Pp 110003- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	alcohol dehydrogenase 5 ADH5 brown adipose tissue BAT heat shock factor 1 HSF1 Biology (General) QH301-705.5
spellingShingle	alcohol dehydrogenase 5 ADH5 brown adipose tissue BAT heat shock factor 1 HSF1 Biology (General) QH301-705.5 Sara C. Sebag Zeyuan Zhang Qingwen Qian Mark Li Zhiyong Zhu Mikako Harata Wenxian Li Leonid V. Zingman Limin Liu Vitor A. Lira Matthew J. Potthoff Alexander Bartelt Ling Yang ADH5-mediated NO bioactivity maintains metabolic homeostasis in brown adipose tissue
description	Summary: Brown adipose tissue (BAT) thermogenic activity is tightly regulated by cellular redox status, but the underlying molecular mechanisms are incompletely understood. Protein S-nitrosylation, the nitric-oxide-mediated cysteine thiol protein modification, plays important roles in cellular redox regulation. Here we show that diet-induced obesity (DIO) and acute cold exposure elevate BAT protein S-nitrosylation, including UCP1. This thermogenic-induced nitric oxide bioactivity is regulated by S-nitrosoglutathione reductase (GSNOR; alcohol dehydrogenase 5 [ADH5]), a denitrosylase that balances the intracellular nitroso-redox status. Loss of ADH5 in BAT impairs cold-induced UCP1-dependent thermogenesis and worsens obesity-associated metabolic dysfunction. Mechanistically, we demonstrate that Adh5 expression is induced by the transcription factor heat shock factor 1 (HSF1), and administration of an HSF1 activator to BAT of DIO mice increases Adh5 expression and significantly improves UCP1-mediated respiration. Together, these data indicate that ADH5 controls BAT nitroso-redox homeostasis to regulate adipose thermogenesis, which may be therapeutically targeted to improve metabolic health.
format	article
author	Sara C. Sebag Zeyuan Zhang Qingwen Qian Mark Li Zhiyong Zhu Mikako Harata Wenxian Li Leonid V. Zingman Limin Liu Vitor A. Lira Matthew J. Potthoff Alexander Bartelt Ling Yang
author_facet	Sara C. Sebag Zeyuan Zhang Qingwen Qian Mark Li Zhiyong Zhu Mikako Harata Wenxian Li Leonid V. Zingman Limin Liu Vitor A. Lira Matthew J. Potthoff Alexander Bartelt Ling Yang
author_sort	Sara C. Sebag
title	ADH5-mediated NO bioactivity maintains metabolic homeostasis in brown adipose tissue
title_short	ADH5-mediated NO bioactivity maintains metabolic homeostasis in brown adipose tissue
title_full	ADH5-mediated NO bioactivity maintains metabolic homeostasis in brown adipose tissue
title_fullStr	ADH5-mediated NO bioactivity maintains metabolic homeostasis in brown adipose tissue
title_full_unstemmed	ADH5-mediated NO bioactivity maintains metabolic homeostasis in brown adipose tissue
title_sort	adh5-mediated no bioactivity maintains metabolic homeostasis in brown adipose tissue
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/fa993ffe513b402bb490e9e9850283d2
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ADH5-mediated NO bioactivity maintains metabolic homeostasis in brown adipose tissue

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