{"doi":"10.1016/j.celrep.2021.110003","title":"ADH5-mediated NO bioactivity maintains metabolic homeostasis in brown adipose tissue","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.","journal":"Cell Reports","year":2021,"id":172062,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":26,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.95,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":695415,"name":"Zeyuan Zhang","orcid":"0000-0002-6372-0086","position":1,"is_corresponding":false},{"id":696058,"name":"Qingwen Qian","orcid":null,"position":2,"is_corresponding":false},{"id":406959,"name":"Mark Li","orcid":"0000-0003-2289-663X","position":3,"is_corresponding":false},{"id":413571,"name":"Zhiyong Zhu","orcid":"0009-0009-7671-7490","position":4,"is_corresponding":false},{"id":571439,"name":"Mikako Harata","orcid":"0000-0003-0459-9412","position":5,"is_corresponding":false},{"id":707604,"name":"Wenxian Li","orcid":"0000-0003-1618-373X","position":6,"is_corresponding":false},{"id":413573,"name":"Leonid V. Zingman","orcid":"0000-0002-7566-4616","position":7,"is_corresponding":false},{"id":707605,"name":"Limin Liu","orcid":"0000-0003-0670-5338","position":8,"is_corresponding":false},{"id":612656,"name":"Vitor A. Lira","orcid":"0000-0002-3162-3804","position":9,"is_corresponding":false},{"id":239933,"name":"Matthew J. Potthoff","orcid":"0000-0001-9158-5128","position":10,"is_corresponding":false},{"id":484611,"name":"Alexander Bartelt","orcid":"0000-0001-7840-3991","position":11,"is_corresponding":false},{"id":510394,"name":"Ling Yang","orcid":"0000-0002-3105-3063","position":12,"is_corresponding":false},{"id":708229,"name":"Sara C. Sebag","orcid":null,"position":0,"is_corresponding":true}],"reference_count":112,"raw_metadata":null,"created_at":"2026-07-18T23:46:37.150824Z","pmid":"34788615","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}