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

Sebag, Sara C.; Zhang, Zeyuan; Qian, Qingwen; Li, Mark; Zhu, Zhiyong; Harata, Mikako; Li, Wenxian; Zingman, Leonid V.; Liu, Limin; Lira, Vitor A.; Potthoff, Matthew J.; Bartelt, Alexander und Yang, Ling (2021): ADH5-mediated NO bioactivity maintains metabolic homeostasis in brown adipose tissue. In: Cell Reports, Bd. 37, Nr. 7, 110003

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2211-1247
• Sprache: Englisch