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1 Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai 200241, China.
2 Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
3 Department of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
4 Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai 200241, 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.
5 Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai 200241, China. Electronic address: qzhang@bio.ecnu.edu.cn.
6 Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China; Department of Endocrinology and Metabolism, Fengxian Central Hospital Affiliated to Southern Medical University, Shanghai 201499, China. Electronic address: alfredhc@sjtu.edu.cn.
7 Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai 200241, 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. Electronic address: lyxu@bio.ecnu.edu.cn.
8 Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai 200241, China; Department of Endocrinology and Metabolism, Fengxian Central Hospital Affiliated to Southern Medical University, Shanghai 201499, 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. Electronic address: xrma@bio.ecnu.edu.cn.
1 Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai 200241, China.
2 Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
3 Department of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
4 Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai 200241, 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.
5 Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai 200241, China. Electronic address: qzhang@bio.ecnu.edu.cn.
6 Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China; Department of Endocrinology and Metabolism, Fengxian Central Hospital Affiliated to Southern Medical University, Shanghai 201499, China. Electronic address: alfredhc@sjtu.edu.cn.
7 Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai 200241, 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. Electronic address: lyxu@bio.ecnu.edu.cn.
8 Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai 200241, China; Department of Endocrinology and Metabolism, Fengxian Central Hospital Affiliated to Southern Medical University, Shanghai 201499, 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. Electronic address: xrma@bio.ecnu.edu.cn.
Beige fat plays key roles in the regulation of systemic energy homeostasis; however, detailed mechanisms and safe strategy for its activation remain elusive. In this study, we discovered that local hyperthermia therapy (LHT) targeting beige fat promoted its activation in humans and mice. LHT achieved using a hydrogel-based photothermal therapy activated beige fat, preventing and treating obesity in mice without adverse effects. HSF1 is required for the effects since HSF1 deficiency blunted the metabolic benefits of LHT. HSF1 regulates Hnrnpa2b1 (A2b1) transcription, leading to increased mRNA stability of key metabolic genes. Importantly, analysis of human association studies followed by functional analysis revealed that the HSF1 gain-of-function variant p.P365T is associated with improved metabolic performance in humans and increased A2b1 transcription in mice and cells. Overall, we demonstrate that LHT offers a promising strategy against obesity by inducing beige fat activation via HSF1-A2B1 transcriptional axis.
Keywords:
HNRNPA2B1; HSF1; beige fat; local hyperthermia therapy; obesity; thermogenesis.
