Details

Autor(en) / Beteiligte

• Lee, Seung-Min
• Lee, Seol Hee
• Jung, Youngae
• Lee, Younglang
• Yoon, Jong Hyun
• Choi, Jeong Yi
• Hwang, Chae Young
• Son, Young Hoon
• Park, Sung Sup
• Hwang, Geum-Sook
• Lee, Kwang-Pyo
• Kwon, Ki-Sun

Titel

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

Ist Teil von

• Nature communications, 2020-11, Vol.11 (1), p.5661-5661, Article 5661

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2020

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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. Ageing leads to a loss of muscle mass and strength, called sarcopenia. Here, the authors show that fatty acid binding protein 3 (FABP3), a lipid chaperone, drives age-dependent lipidome remodeling in skeletal muscle and deteriorates muscle mass and contractility by modulating membrane fluidity and ER stress signaling.