ArticlePLoS genetics2025
A distal enhancer of Pparα regulates thermogenesis and mitochondrial function in brown fat.
Article in PLoS genetics, 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
- Mechanisms of energy metabolism reprogramming and homeostasis maintenance in overwintering hibernating animals.Frontiers in veterinary science · 2026Review
- Brown adipose tissue in ruminants: development, thermogenic function, and nutritional regulation.Frontiers in veterinary science · 2026Review
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Authors and funding
12 authors.
Funding
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Abstract
Peroxisome proliferator-activated receptor α (PPARα) is a crucial transcription factor in regulating brown adipose tissue (BAT) physiological function. However, the mechanisms of enhancer-promoter chromatin interactions that control transcription regulation of Pparα in BAT remain unclear. In this study, we used circularized chromosome conformation capture coupled with next-generation sequencing (4C-seq) to reveal distinct differences in Pparα-associated chromatin interactions between intrascapular BAT (iBAT) and epididymal white adipose tissue (eWAT). In addition, we identified an iBAT-specific active enhancer (Pparα-En4) that was activated by cold stimulation. Functional assays demonstrated that targeted repression of Pparα-En4 region significantly decreased Pparα expression and impaired brown adipocyte differentiation and thermogenesis. Moreover, the transcription factor CREB regulated Pparα-En4 activity and increased Pparα expression in cooperation with the acetyltransferase CBP. Repression of Pparα-En4 using a lentiviral system in iBAT resulted in reduced thermogenic capacity and mitochondrial damage during cold acclimation conditions in vivo. These findings reveal that Pparα-En4 is a critical regulatory element in thermogenesis and mitochondrial function, and provide important insights into enhancer-mediated transcriptional regulation of Pparα expression in BAT.
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Registered trials
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