DataVXAdvanced SciencePaper
journal article·2023-09Open access

Rna M6a Methylation Regulates Glycolysis of Beige Fat and Contributes to Systemic Metabolic Homeostasis

Yu Li, Yankang Zhang, Ting Zhang, Xiaodan Ping, Dongmei Wang, Yanru Chen, Jian Yu, Caizhi Liu, Ziqi Liu, Yuhan Zheng, Yongfeng Yang, Chengchao Ruan, Dali Li, Zhenyu Du, Jiqiu Wang, Lingyan Xu, Xinran Ma

Advanced Science· Volume 10· Issue 25
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Abstract

Abstract N6‐methyladenosine (m6A) modification has been implicated in the progression of obesity and metabolic diseases. However, its impact on beige fat biology is not well understood. Here, via m6A‐sequencing and RNA‐sequencing, this work reports that upon beige adipocytes activation, glycolytic genes undergo major events of m6A modification and transcriptional activation. Genetic ablation of m6A writer Mettl3 in fat tissues reveals that Mettl3 deficiency in mature beige adipocytes leads to suppressed glycolytic capability and thermogenesis, as well as reduced preadipocytes proliferation via glycolytic product lactate. In addition, specific modulation of Mettl3 in beige fat via AAV delivery demonstrates consistently Mettl3's role in glucose metabolism, thermogenesis, and beige fat hyperplasia. Mechanistically, Mettl3 and m6A reader Igf2bp2 control mRNA stability of key glycolytic genes in beige adipocytes. Overall, these findings highlight the significance of m6A on fat biology and systemic energy homeostasis.
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Research context

OpenAlex topics: RNA modifications and cancer · Adipose Tissue and Metabolism · Cancer-related molecular mechanisms research

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

Affiliations

Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and 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

Department of Endocrinology and Metabolism Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 China

Department of Endocrinology and Metabolism Fengxian Central Hospital Affiliated to Southern Medical University Shanghai 201499 China

Department of Physiology and Pathophysiology School of Basic Medical Sciences Fudan University Shanghai 200032 China

Shanghai Frontiers Science Center of Genome Editing and Cell Therapy Shanghai Key Laboratory of Regulatory Biology and School of Life Sciences East China Normal University Shanghai 200241 China

Funding

National Natural Science Foundation of China · National Key Research and Development Program of China · Science and Technology Commission of Shanghai Municipality · Fundamental Research Funds for the Central Universities

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