Macrophage SREBP1 regulates skeletal muscle regeneration

• DOI: 10.3389/fimmu.2023.1251784
• Publication Date: 2024-01-08T04:20:51Z
• Authors: Yumiko Oishi; Hiroyuki Koike; Naoki Kumagami; Yoshimi Nakagawa; Masaya Araki; Yoshitaka Taketomi; Yoshimi Miki; Shigeru Matsuda; Hyeree Kim; Takashi Matsuzaka; Hitoshi Ozawa; Hitoshi Shimano; Makoto Murakami; Ichiro Manabe
• Keywords: 0303 health sciences; Macrophages; Immunology; macrophage; RC581-607; SREBP (sterol regulatory element-binding protein) pathway; Mice; 03 medical and health sciences; fatty acid metabolism; skeletal muscle regeneration; Regeneration; Animals; Immunologic diseases. Allergy; Muscle, Skeletal; Sterol Regulatory Element Binding Protein 1; Phospholipids; EPA - 20:5n-3

Macrophages are essential for the proper inflammatory and reparative processes that lead to regeneration of skeletal muscle after injury. Recent studies have demonstrated close links between function activated macrophages their cellular metabolism. Sterol regulatory element-binding protein 1 (SREBP1) is a key regulator lipid metabolism has been shown affect states macrophages. However, its role in tissue repair poorly understood. Here we show systemic deletion Srebf1, encoding SREBP1, or macrophage-specific Srebf1a, SREBP1a, delays resolution inflammation impairs Srebf1 deficiency mitochondrial suppresses accumulation at sites Lipidomic analyses showed reduction major phospholipid species -/- myeloid cells. Moreover, diet supplementation with eicosapentaenoic acid restored gene expression improved regeneration. Collectively, our results demonstrate SREBP1 injury suggest SREBP1-mediated fatty remodeling critical macrophage repair.