ArticleExperimental & molecular medicine2025
SENP2 regulates UCP1-dependent thermogenesis in brown adipocytes via deSUMOylation of ERRα.
Article in Experimental & molecular medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Alternative Receptor Signaling for the Selective and Multifaceted Regulation of Human Brown Adipocytes.International journal of molecular sciences · 2026Review
- Bioactive Constituents and Therapeutic Mechanisms of Shenfu Decoction in a Rat Model of Seawater-Immersion-Induced Accidental Hypothermia.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Genomic Structural Equation Modeling Reveals Cardiovascular-Kidney-Metabolic Syndrome Genetic Architecture.Journal of diabetes · 2026Article
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7 authors.
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Abstract
Brown adipose tissue (BAT) is responsible for energy homeostasis and adaptive thermogenesis. SUMO-specific protease 2 (SENP2) plays an essential role in adipogenesis; however, the role of SENP2 in BAT metabolism has not been explored. Here we investigated the role of SENP2 in mature brown adipocytes with a brown adipocyte-specific SENP2 knockout (Senp2-BKO) mouse model generated using the uncoupling protein 1 (Ucp1)-Cre. High-fat diet-induced insulin resistance was aggravated in Senp2-BKO mice compared with control mice. In Senp2-BKO mice, adaptive thermogenesis upon acute cold exposure was impaired and UCP1 expression was barely induced upon cold or β-adrenergic stimulation. SENP2-mediated deSUMOylation of estrogen-related receptor alpha (ERRα) significantly enhanced Ucp1 promoter activity through activation of the ERRα/PGC1α complex. The absence of SENP2 inhibited formation of ERRα, cAMP-response element-binding protein (CREB) and RNA Polymerase II transcriptional complex at the Ucp1 promoter following β3-adrenergic stimulation. In addition, SUMOylation of ERRα severely interfered with binding of ERRα to its DNA-binding site (ERRE) in the promoter of Ucp1. Our findings revealed that SENP2 plays a role in the metabolic flexibility and thermogenic efficiency of BAT, particularly in response to β3-adrenergic activation.
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