Local hyperthermia therapy induces browning of white fat and treats obesity

Yu Li; Dongmei Wang; Xiaodan Ping; Yankang Zhang; Ting Zhang; Li Wang; Li Jin; Wenjun Zhao; Mingwei Guo; Fei Shen; Meiyao Meng; Xin Chen; Ying Zheng; Jiqiu Wang; Dali Li; Qiang Zhang; Cheng Hu; Lingyan Xu; Xinran Ma

doi:10.1016/j.cell.2022.02.004

Local hyperthermia therapy induces browning of white fat and treats obesity

Cell. 2022 Mar 17;185(6):949-966.e19. doi: 10.1016/j.cell.2022.02.004. Epub 2022 Mar 4.

Authors

Yu Li¹, Dongmei Wang¹, Xiaodan Ping¹, Yankang Zhang¹, Ting Zhang¹, Li Wang¹, Li Jin², Wenjun Zhao¹, Mingwei Guo¹, Fei Shen¹, Meiyao Meng¹, Xin Chen¹, Ying Zheng¹, Jiqiu Wang³, Dali Li⁴, Qiang Zhang⁵, Cheng Hu⁶, Lingyan Xu⁷, Xinran Ma⁸

Affiliations

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.

PMID: 35247329
DOI: 10.1016/j.cell.2022.02.004

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue, Beige* / metabolism
Adipose Tissue, Brown / metabolism
Adipose Tissue, White* / metabolism
Animals
Hyperthermia, Induced*
Mice
Mice, Inbred C57BL
Obesity / metabolism
Obesity / therapy*