DataVXAdvanced SciencePaper
journal article·2026-02Open access

Gabpα‐Pparγ Complex Determines Glycolytic Capacity and Lactic Acid Homeostasis in Brown Fat

Zhihan Wang, Huanyu Wang, Qianqian Kang, Ruping Pan, Rui He, Min Yang, Jiadai Liu, Xuemin Peng, Yuyu Xie, Hongyan Deng, Wenshe Wang, Zengzhe Zhu, Jing Ge, Yulian Liu, Ronghui Gao, Yaming Guo, Peng Yu, Limeng Pan, Danpei Li, Pema Maretich, Xiaoping Luo, Xuefeng Yu, Yong Chen

Advanced Science· Volume 13· Issue 8
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Abstract

Abstract Glycolysis in brown adipose tissue (BAT) plays a critical role in fueling thermogenesis. However, the transcriptional control of glycolysis in brown fat remains poorly understood. Here, GA binding protein alpha chain (Gabpα) is identified as a key transcriptional regulator that sustains the glycolytic capacity of brown adipocytes. Gabpα is preferentially expressed in BAT, yet BAT‐specific ablation of Gabpα substantially impairs glycolytic flux and heat production, leading to reduced glucose tolerance and impaired cold tolerance. Mechanistically, the C‐terminus of the Gabpα protein directly interacts with peroxisome proliferator‐activated receptor‐γ (Pparγ) and synergistically promotes transcription of the glycolytic gene enolase 1 ( Eno1 ). Disruption of the Gabpα–Pparγ interaction in BAT significantly suppresses glycolysis, reduces energy expenditure, and induces cold intolerance in mice. Notably, inhibition of Gabpα‐Pparγ binding also decreases lactic acid concentration and downregulates lactate dehydrogenase (Ldh) expression, resulting in the suppression of uncoupling protein 1 (Ucp1) expression and thermogenesis. Conversely, adipose‐specific overexpression of Gabpα markedly enhances BAT glycolytic and thermogenic activity, protecting against cold challenge and high‐fat diet (HFD)‐induced obesity. Collectively, these results point to the Gabpα‐Pparγ complex as a potent regulator of glycolysis in BAT and may represent a promising therapeutic target for metabolic disease intervention.
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Research context

OpenAlex topics: Adipose Tissue and Metabolism · Adipokines, Inflammation, and Metabolic Diseases · Peroxisome Proliferator-Activated Receptors

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

Affiliations

Division of Endocrinology Department of Internal Medicine Tongji Hospital Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases Huazhong University of Science and Technology Wuhan 430030 China

Laboratory of Endocrinology and Metabolism Ministry of Education Key Laboratory of Vascular Aging Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430000 China

Department of Pediatrics Hubei Provincial Key Laboratory of Pediatric Genetic Metabolic and Endocrine Rare Diseases Hubei Provincial Clinical Research Center for Children's Growth and Development and Metabolic Diseases Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China

Department of Nuclear Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China

Research Laboratory of Electronics and Department of Biology Massachusetts Institute of Technology Cambridge MA 02139 USA

Hubei Clinical Medical Research Center for Endocrinology and Metabolic Diseases Branch of National Clinical Research Center for Metabolic Diseases Hubei 430000 China

Funding

National Natural Science Foundation of China · National Key Research and Development Program of China

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