Skeletal muscle-secreted DLPC orchestrates systemic energy homeostasis by enhancing adipose browning

Xiaodi Hu, Mingwei Sun, Qian Chen, Yixia Zhao, Na Liang, Siyuan Wang, Pengbin Yin, Yuanping Yang, Sin Man Lam, Qianying Zhang, Alimujiang Tudiyusufu, Yingying Gu, Xin Wan, Meihong Chen, Hu Li, Xiaofei Zhang, Guanghou Shui, Suneng Fu, Licheng Zhang, Peifu Tang, Catherine C. L. Wong, Yong Zhang () and Dahai Zhu ()
Additional contact information
Xiaodi Hu: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College
Mingwei Sun: Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory)
Qian Chen: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College
Yixia Zhao: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College
Na Liang: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College
Siyuan Wang: Chinese Academy of Medical Science & Peking Union Medical College
Pengbin Yin: The Fourth Medical Center of Chinese PLA General Hospital
Yuanping Yang: Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory)
Sin Man Lam: LipidALL Technologies Company Limited
Qianying Zhang: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College
Alimujiang Tudiyusufu: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College
Yingying Gu: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College
Xin Wan: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College
Meihong Chen: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College
Hu Li: Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory)
Xiaofei Zhang: Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory)
Guanghou Shui: LipidALL Technologies Company Limited
Suneng Fu: Guangzhou Laboratory
Licheng Zhang: The Fourth Medical Center of Chinese PLA General Hospital
Peifu Tang: The Fourth Medical Center of Chinese PLA General Hospital
Catherine C. L. Wong: Chinese Academy of Medical Science & Peking Union Medical College
Yong Zhang: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College
Dahai Zhu: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract MyoD is a skeletal muscle-specifically expressed transcription factor and plays a critical role in regulating myogenesis during muscle development and regeneration. However, whether myofibers-expressed MyoD exerts its metabolic function in regulating whole body energy homeostasis in vivo remains largely unknown. Here, we report that genetic deletion of Myod in male mice enhances the oxidative metabolism of muscle and, intriguingly, renders the male mice resistant to high fat diet-induced obesity. By performing lipidomic analysis in muscle-conditioned medium and serum, we identify 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC) as a muscle-released lipid that is responsible for MyoD-orchestrated body energy homeostasis in male Myod KO mice. Functionally, the administration of DLPC significantly ameliorates HFD-induced obesity in male mice. Mechanistically, DLPC is found to induce white adipose browning via lipid peroxidation-mediated p38 signaling in male mice. Collectively, our findings not only uncover a novel function of MyoD in controlling systemic energy homeostasis through the muscle-derived lipokine DLPC but also suggest that the DLPC might have clinical potential for treating obesity in humans.

Date: 2023
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DOI: 10.1038/s41467-023-43402-z

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