Identification of a distal enhancer of Ucp1 essential for thermogenesis and mitochondrial function in brown fat
Su D., Jiang T., Song Y., Li D., Zhan S., Zhong T.
Animal Study, published in Commun Biol (2025) — summary generated from the PubMed abstract.
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Animal Study
- Journal
- Commun Biol (2025)
- Reported sample size
- —
- Source database
- Europe PMC
- PMID
- 39789228
- PMCID
- PMC11718246
- DOI
- 10.1038/s42003-025-07468-3
- Citations
- 3
Abstract (original English)
Uncoupling protein 1 (UCP1) is a crucial protein located in the mitochondrial inner membrane that mediates nonshivering thermogenesis. However, the molecular mechanisms by which enhancer-promoter chromatin interactions control Ucp1 transcriptional regulation in brown adipose tissue (BAT) are unclear. Here, we employed circularized chromosome conformation capture coupled with next-generation sequencing (4C-seq) to generate high-resolution chromatin interaction profiles of Ucp1 in interscapular brown adipose tissue (iBAT) and epididymal white adipose tissue (eWAT) and revealed marked changes in Ucp1 chromatin interaction between iBAT and eWAT. Next, we identified four iBAT-specific active enhancers of Ucp1, and three of them were activated by cold stimulation. Transcriptional repression of the Ucp1-En4 or Ucp1-En6 region significantly downregulated Ucp1 and impaired mitochondrial function in brown adipocytes. Furthermore, depletion of the cohesin subunit RAD21 decreased the interaction intensity between Ucp1-En4 and the Ucp1 promoter and downregulated Ucp1. EBF2 cooperated with the acetyltransferase CBP to regulate Ucp1-En4 activity and increase Ucp1 transcriptional activity. In vivo, lentivirus-mediated repression of Ucp1-En4 was injected into iBAT, resulting in impacted iBAT thermogenic capacity and impaired iBAT mitochondrial function under cold acclimation conditions. Studyin
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
- • This is preclinical work; animal or laboratory results cannot be applied to humans.
Evidence level
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
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