Skeletal muscle-secreted DLPC orchestrates systemic energy homeostasis by enhancing adipose browning
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Published:2023-11-30
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Hu Xiaodi, Sun Mingwei, Chen Qian, Zhao Yixia, Liang Na, Wang Siyuan, Yin PengbinORCID, Yang Yuanping, Lam Sin ManORCID, Zhang Qianying, Tudiyusufu Alimujiang, Gu Yingying, Wan XinORCID, Chen Meihong, Li Hu, Zhang XiaofeiORCID, Shui GuanghouORCID, Fu Suneng, Zhang Licheng, Tang Peifu, Wong Catherine C. L.ORCID, Zhang YongORCID, Zhu DahaiORCID
Abstract
AbstractMyoD 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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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