Evidence map›Paper›PMID 40971725›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

NRF2-REGγ-ACADM/KLF15 Signaling Pathway Regulates the Browning of White Adipose Tissue to Modulate Obesity.

Hui Chen, Qiujing Guan, Shuangming Gong, Yingying Du, Zhidan Zhang, Yan Liu, Lei Zhou, Lin Liu, Baoquan Xin, Yilan Guo and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
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

16 authors.

Hui ChenDepartment of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, 200240, China.
Qiujing GuanShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Shuangming GongShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Yingying DuShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Zhidan ZhangDepartment of Preventive Treatment of disease by Traditional Chinese Medicine, Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China.
Yan LiuShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Lei ZhouDepartment of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.
Lin LiuShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Baoquan XinDepartment of Orthopaedic Oncology, Changzheng Hospital, Navy Medical University, Shanghai, 200003, China.
Yilan GuoThe Key Laboratory of Adolescent Health Assessment and Exercise Intervention of the Ministry of Education, East China Normal University, Shanghai, 200241, China.
Hui ZhangDepartment of Clinical Laboratory, Shanghai Fifth People's Hospital, Fudan University, Shanghai, 200240, China.
Ziyang ZhouDepartment of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, 200240, China.
Tongchao PeiDepartment of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, 200240, China.
Guohong YuDepartment of Emergency Medicine, Baoshan Second People's Hospital, Baoshan College of Traditional Chinese Medicine, 678000, Yunnan, China.
Sokun YinDepartment of Emergency Medicine, Luoping County People's Hospital, 655800, Yunnan, China.
Lei LiJoint Center for Translational Medicine, Shanghai Fifth People's Hospital, Fudan University, and School of Life Science, East China Normal University, Shanghai, 200241, China.ORCID https://orcid.org/0000-0002-3114-1653

Funding

National Natural Proton Cluster Incubation Project of Shanghai Fifth People's Hospital 2024GZRZZTFY01National Natural Science Foundation of China 82372456Natural Science Foundation of Chongqing CSTB2024NSCQ-JQX0009Shanghai Pilot Program for Basic Research TQ20240208Talent Development Project of Shanghai Fifth People's Hospital 2024WYRCJY02
6 · The paper itself

Abstract

Obesity is a significant risk factor for diabetes, cardiovascular diseases, and certain cancers, and manifests as excessive fat accumulation. The browning of white adipose tissue (WAT) represents one of the most promising strategies for preventing and treating obesity and metabolic diseases. To date, an increasing number of studies have focused on key molecular mechanisms regulating fat thermogenesis, laying the foundation for effective intervention strategies. Here, REGγ expression is shown to be significantly upregulated in adipose tissue of obese individuals and in inguinal WAT (iWAT) of obese mice. Deficiency in REGγ expression reduces fat deposition, increases energy expenditure in adipose tissue, and protects mice from HFD-induced obesity and insulin resistance. Mechanistically, REGγ expression regulates browning of WAT by modulating ACADM and KLF15-UCP1 signaling in a ubiquitin-independent degradation manner. Overactivation of the NRF2-REGγ axis facilitates adipose tissue function to cause obesity. Notably, inhibition of REGγ in the iWAT alleviates HFD-induced obesity, thereby identifying REGγ as a latent target for obesity treatment. Together, the findings provide new targets for intervening in obesity and might ultimately offer new options for treating obesity.

Indexed as

Adipose Tissue, BrownAdipose Tissue, WhiteKruppel-Like Transcription FactorsNF-E2-Related Factor 2ObesityAnimalsHumansMaleMiceMice, Inbred C57BLSignal TransductionThermogenesisKlf15 protein, mouseKruppel-Like Transcription FactorsNfe2l2 protein, mouseNF-E2-Related Factor 2browning of white adipose tissueobesityPSME3ubiquitin‐independent protein degradation

Identifiers

PMID40971725
PMCPMC12697771

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.