DataVXAdvanced SciencePaper
journal article·2025-12Open access

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, Hui Zhang, Ziyang Zhou, Tongchao Pei, Guohong Yu, Sokun Yin, Lei Li

Advanced Science· Volume 12· Issue 46
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Abstract

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.
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Research context

Materials processing

OpenAlex topics: Adipose Tissue and Metabolism · Adipokines, Inflammation, and Metabolic Diseases · Cardiovascular Disease and Adiposity

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Trauma‐Emergency & Critical Care Medicine Shanghai Fifth People's Hospital Fudan University Shanghai 200240 China

Joint Center for Translational Medicine Shanghai Fifth People's Hospital Fudan University, and School of Life Science East China Normal University Shanghai 200241 China

Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences School of Life Sciences East China Normal University Shanghai 200241 China

Department of Preventive Treatment of disease by Traditional Chinese Medicine Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai 200062 China

Department of Orthopedics Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200080 China

Department of Orthopaedic Oncology Changzheng Hospital Navy Medical University Shanghai 200003 China

The Key Laboratory of Adolescent Health Assessment and Exercise Intervention of the Ministry of Education East China Normal University Shanghai 200241 China

Department of Clinical Laboratory Shanghai Fifth People's Hospital Fudan University Shanghai 200240 China

Department of Emergency Medicine Baoshan Second People's Hospital Baoshan College of Traditional Chinese Medicine 678000 Yunnan China

Department of Emergency Medicine Luoping County People's Hospital 655800 Yunnan China

School of Life Sciences East China Normal University Shanghai 200241 China

Chongqing Key Laboratory of Precision Optics Chongqing Institute of East China Normal University Chongqing 401120 China

Funding

National Natural Science Foundation of China · Natural Science Foundation of Chongqing Municipality

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