GPX4 is not required for the thermogenesis function of brown adipose tissue in mice
*Correspondence to:
Zhenyu Ju, Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Department of Developmental & Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, Guangdong, China.
E-mail: zhenyuju2016@jnu.edu.cn
Fudi Wang, The Second Affiliated Hospital, School of Public Health, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang, China. E-mail: fwang@zju.edu.cn
Qian Hu, Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Department of Developmental & Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, Guangdong, China. E-mail: huqian@jnu.edu.cn
Fudi Wang, The Second Affiliated Hospital, School of Public Health, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang, China. E-mail: fwang@zju.edu.cn
Qian Hu, Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Department of Developmental & Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, Guangdong, China. E-mail: huqian@jnu.edu.cn
Ferroptosis Oxid Stress. 2026;2:202616. 10.70401/fos.2026.0033
Received: April 14, 2026Accepted: June 18, 2026Published: June 18, 2026
This manuscript is made available in its unedited form to allow early access to the
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Abstract
Aims: Brown adipose tissue (BAT) relies heavily on mitochondrial activity and reactive oxygen species homeostasis to regulate thermogenesis and metabolic balance. However, the specific role of glutathione peroxidase 4 (GPX4), a critical antioxidant enzyme and central regulator of ferroptosis, in BAT remains unclear. This study aims to investigate the necessity of GPX4 for the functional integrity and thermogenic capacity of BAT.
Methods: We generated a genetically engineered mouse model with a BAT-specific knockout of the Gpx4 gene. The physiological and metabolic impacts of GPX4 deficiency were evaluated across three different dietary contexts: cold exposure condition, high-fat diet, and vitamin E-deficient diet. Furthermore, RNA sequencing (RNA-seq) was conducted to analyze transcriptomic changes within the tissue.
Results: Phenotypic and metabolic analyses indicated that the absence of GPX4 does not impair the thermogenic function of BAT under any of the tested dietary conditions. Consistent with these physiological findings, RNA-seq revealed that GPX4 deficiency does not significantly alter the expression levels of genes associated with ferroptosis or thermogenic pathways.
Conclusion: Despite its crucial role in preventing ferroptosis in other tissues, GPX4 is not essential for maintaining the functional integrity and thermogenesis of BAT in mice under the specific physiological conditions tested.
Keywords
Glutathione peroxidase 4, thermogenesis, brown adipose tissue
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Zhang Y, Li C, Liu Y, Wang W, You W, Ju Z, et al. GPX4 is not required for the thermogenesis function of brown adipose tissue in mice. Ferroptosis Oxid Stress. 2026;2:202616. https://doi.org/10.70401/fos.2026.0033
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Zhang Y, Li C, Liu Y, Wang W, You W, Ju Z, et al. GPX4 is not required for the thermogenesis function of brown adipose tissue in mice. Ferroptosis Oxid Stress. 2026;2:202616. https://doi.org/10.70401/fos.2026.0033
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