Naringenin improves muscle endurance via activation of the Sp1-ERRγ transcriptional axis

Zhenyu Lv; Jiao Meng; Sheng Yao; Fu Xiao; Shilong Li; Haoyang Shi; Chen Cui; Kaixian Chen; Xiaomin Luo; Yang Ye; Chang Chen

doi:10.1016/j.celrep.2023.113288

Naringenin improves muscle endurance via activation of the Sp1-ERRγ transcriptional axis

Cell Rep. 2023 Nov 28;42(11):113288. doi: 10.1016/j.celrep.2023.113288. Epub 2023 Oct 23.

Authors

Zhenyu Lv¹, Jiao Meng², Sheng Yao³, Fu Xiao⁴, Shilong Li¹, Haoyang Shi¹, Chen Cui⁵, Kaixian Chen⁶, Xiaomin Luo⁷, Yang Ye⁸, Chang Chen⁹

Affiliations

¹ National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
² National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
³ State Key Laboratory of Drug Research and Natural Products Chemistry Department, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China.
⁴ School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; Drug and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
⁵ University of Chinese Academy of Sciences, Beijing 100049, China; Drug and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
⁶ University of Chinese Academy of Sciences, Beijing 100049, China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; Drug and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
⁷ University of Chinese Academy of Sciences, Beijing 100049, China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; Drug and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: xmluo@simm.ac.cn.
⁸ State Key Laboratory of Drug Research and Natural Products Chemistry Department, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201203, China. Electronic address: yye@simm.ac.cn.
⁹ National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China. Electronic address: changchen@moon.ibp.ac.cn.

PMID: 37874675
DOI: 10.1016/j.celrep.2023.113288

Abstract

Skeletal muscle function declines in the aging process or disease; however, until now, skeletal muscle has remained one of the organs most undertreated with medication. In this study, naringenin (NAR) was found to build muscle endurance in wild-type mice of different ages by increasing oxidative myofiber numbers and aerobic metabolism, and it ameliorates muscle dysfunction in mdx mice. The transcription factor Sp1 was identified as a direct target of NAR and was shown to mediate the function of NAR on muscle. Moreover, the binding site of NAR on Sp1 was further validated as GLN-110. NAR enhances the binding of Sp1 to the CCCTGCCCTC sequence of the Esrrg promoter by promoting Sp1 phosphorylation, thus upregulating Esrrg expression. The identification of the Sp1-ERRγ transcriptional axis is of great significance in basic muscle research, and this function of NAR has potential implications for the improvement of muscle function and the prevention of muscle atrophy.

Keywords: CP: Metabolism; CP: Molecular biology; Duchenne muscular dystrophy; energy metabolism; fiber type; muscle atrophy; naringenin; skeletal muscle.

Publication types

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

MeSH terms

Animals
Mice
Mice, Inbred mdx
Muscle, Skeletal / metabolism
Muscular Dystrophy, Duchenne* / metabolism
Promoter Regions, Genetic / genetics

Substances

naringenin