2. Academic Validation
  3. FABP3-mediated membrane lipid saturation alters fluidity and induces ER stress in skeletal muscle with aging

FABP3-mediated membrane lipid saturation alters fluidity and induces ER stress in skeletal muscle with aging

  • Nat Commun. 2020 Nov 9;11(1):5661. doi: 10.1038/s41467-020-19501-6.
Seung-Min Lee 1,  Seol Hee Lee 1 2,  Youngae Jung 3,  Younglang Lee 4,  Jong Hyun Yoon 1 5,  Jeong Yi Choi 1,  Chae Young Hwang 1,  Young Hoon Son 1,  Sung Sup Park 1 2,  Geum-Sook Hwang 3,  Kwang-Pyo Lee 6 7 8,  Ki-Sun Kwon 9 10 11
Affiliations

Affiliations

  • 1 Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea.
  • 2 Department of Biomolecular Science, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon, 34113, Republic of Korea.
  • 3 Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul, 03759, Republic of Korea.
  • 4 Aventi Inc., Daejeon, 34141, Republic of Korea.
  • 5 Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon, 34113, Republic of Korea.
  • 6 Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea. [email protected].
  • 7 Department of Biomolecular Science, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon, 34113, Republic of Korea. [email protected].
  • 8 Aventi Inc., Daejeon, 34141, Republic of Korea. [email protected].
  • 9 Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea. [email protected].
  • 10 Aventi Inc., Daejeon, 34141, Republic of Korea. [email protected].
  • 11 Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon, 34113, Republic of Korea. [email protected].
PMID: 33168829 DOI: 10.1038/s41467-020-19501-6
Abstract

Sarcopenia is characterized by decreased skeletal muscle mass and function with age. Aged muscles have altered lipid compositions; however, the role and regulation of lipids are unknown. Here we report that FABP3 is upregulated in aged skeletal muscles, disrupting homeostasis via lipid remodeling. Lipidomic analyses reveal that FABP3 overexpression in young muscles alters the membrane lipid composition to that of aged muscle by decreasing polyunsaturated phospholipid acyl chains, while increasing sphingomyelin and lysophosphatidylcholine. FABP3-dependent membrane lipid remodeling causes ER stress via the PERK-eIF2α pathway and inhibits protein synthesis, limiting muscle recovery after immobilization. FABP3 knockdown induces a young-like lipid composition in aged muscles, reduces ER stress, and improves protein synthesis and muscle recovery. Further, FABP3 reduces membrane fluidity and knockdown increases fluidity in vitro, potentially causing ER stress. Therefore, FABP3 drives membrane lipid composition-mediated ER stress to regulate muscle homeostasis during aging and is a valuable target for sarcopenia.

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