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ADH5-mediated NO bioactivity maintains metabolic homeostasis in brown adipose tissue.
Cell Rep. 37:110003 (2021)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Adh5 ; Bat ; Hsf1 ; Alcohol Dehydrogenase 5 ; Brown Adipose Tissue ; Heat Shock Factor 1 ; Nitrosative Stress ; Obesity; S-nitrosoglutathione Reductase; Nitric-oxide Synthase; Beige Fat Development; Insulin-resistance; Mitochondrial Biogenesis; Blood-flow; Nitrosylation; Obesity; Thermogenesis; Gsnor
ISSN (print) / ISBN
2211-1247
e-ISSN
2211-1247
Journal
Cell Reports
Quellenangaben
Volume: 37,
Issue: 7,
Article Number: 110003
Publisher
Cell Press
Publishing Place
50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes and Cancer (IDC)
Grants
NIH
American Diabetes Association Innovative Basic Science Award
American Heart Association predoctoral award
American Diabetes Association Innovative Basic Science Award
American Heart Association predoctoral award