Evidence map›Paper›PMID 41129595›Full record

ArticlePLoS genetics2025

A distal enhancer of Pparα regulates thermogenesis and mitochondrial function in brown fat.

Tingting Jiang, Duo Su, Jing Ke, Xin Dai, Maohua Wang, Yan Wang, Siyuan Zhan, Tao Zhong, Jiazhong Guo, Li Li and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
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  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Tingting JiangState Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China.
Duo SuState Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China.ORCID https://orcid.org/0000-0002-1308-5862
Jing KeState Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China.ORCID https://orcid.org/0009-0007-9560-5334
Xin DaiState Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China.
Maohua WangState Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China.ORCID https://orcid.org/0009-0008-9585-2383
Yan WangKey Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China.
Siyuan ZhanKey Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China.ORCID https://orcid.org/0000-0003-3449-9682
Tao ZhongKey Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China.
Jiazhong GuoKey Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China.
Li LiKey Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China.
Honping ZhangKey Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China.
Linjie WangState Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China.ORCID https://orcid.org/0000-0001-9672-7703

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Adipose Tissue, BrownEnhancer Elements, GeneticMitochondriaPPAR alphaAdipocytesAdipose Tissue, WhiteAnimalsChromatinCold TemperatureCyclic AMP Response Element-Binding ProteinMaleMiceMice, Inbred C57BLPromoter Regions, GeneticThermogenesisUncoupling Protein 1ChromatinCreb1 protein, mouseCyclic AMP Response Element-Binding ProteinPPAR alphaPpara protein, mouseUcp1 protein, mouseUncoupling Protein 1

Identifiers

PMID41129595
PMCPMC12574865

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.