Journal article
ADH5-mediated NO bioactivity maintains metabolic homeostasis in brown adipose tissue
Cell reports (Cambridge), Vol.37(7), pp.110003-110003
11/16/2021
DOI: 10.1016/j.celrep.2021.110003
PMID: 34788615
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.
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•Thermogenesis induces BAT protein S-nitrosylation modification•ADH5 is required for maintaining BAT metabolic homeostasis•Diet-induced obesity suppresses BAT HSF1-mediated activation of Adh5•ADH5 overexpression ameliorates BAT metabolic dysfunction in the context of obesity
Sebag et al. report that ADH5-mediated nitroso-redox homeostasis regulates brown adipose thermogenesis, and loss of HSF1-Adh5 activation leads to obesity-associated metabolic dysfunction.
Details
- Title: Subtitle
- ADH5-mediated NO bioactivity maintains metabolic homeostasis in brown adipose tissue
- Creators
- Sara C Sebag - University of Iowa, Anatomy and Cell BiologyZeyuan ZhangQingwen Qian - University of Iowa, Anatomy and Cell BiologyMark Li - University of IowaZhiyong Zhu - University of Iowa, Internal MedicineMikako HarataWenxian LiLeonid V Zingman - University of Iowa, Internal MedicineLimin Liu - Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USAVitor A Lira - University of Iowa, Health, Sport, and Human PhysiologyMatthew J Potthoff - University of Iowa, Neuroscience and PharmacologyAlexander Bartelt - Institute for Cardiovascular Prevention, Ludwig Maximilians University Munich Pettenkoferstr. 9, 80336 Munich, GermanyLing Yang - University of Iowa, Anatomy and Cell Biology
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.37(7), pp.110003-110003
- DOI
- 10.1016/j.celrep.2021.110003
- PMID
- 34788615
- NLM abbreviation
- Cell Rep
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100000968, name: American Heart Association, award: 19PRE34380258; DOI: 10.13039/100000002, name: National Institutes of Health, award: R01 DK108835-01A1; DOI: 10.13039/100000041, name: American Diabetes Association, award: 1-18-IBS-149
- Language
- English
- Date published
- 11/16/2021
- Academic Unit
- Molecular Physiology and Biophysics; Anatomy and Cell Biology; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Health, Sport, and Human Physiology ; Internal Medicine
- Record Identifier
- 9984203957802771
Metrics
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