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.
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DOI：
10.1038/s41467-020-19501-6
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发表时间：
2020-11-09
影响因子：
16.6
通讯作者：
Kwon KS
中科院分区：
文献类型：
--
作者：
Lee SM;Lee SH;Jung Y;Lee Y;Yoon JH;Choi JY;Hwang CY;Son YH;Park SS;Hwang GS;Lee KP;Kwon KS
骨骼肌减少症的特征是骨骼肌质量和功能随着年龄的增长而下降。衰老的肌肉改变了脂质组成；然而，脂质的作用和调节尚不清楚。在这里，我们报道FABP3在老年骨骼肌中上调，通过脂质重塑破坏体内平衡。脂质组学分析显示，年轻肌肉中FABP3的过表达通过减少多不饱和磷脂酰基链，增加鞘磷脂和溶血磷脂酰胆碱，改变了膜脂组成与老年肌肉的结构。fabp3依赖的膜脂重塑通过PERK-eIF2α途径引起内质网应激，抑制蛋白质合成，限制固定后的肌肉恢复。FABP3基因敲低可诱导衰老肌肉中类似年轻人的脂质组成，减少内质网应激，促进蛋白质合成和肌肉恢复。此外，FABP3降低了膜的流动性，而敲低则增加了体外流动性，可能导致内质网应激。因此，FABP3驱动膜脂成分介导的内质网应激来调节衰老过程中的肌肉稳态，是肌少症的一个有价值的靶点。衰老会导致肌肉量和力量的减少，称为肌肉减少症。在这里，作者表明脂肪酸结合蛋白3 (FABP3)，一种脂质伴侣，驱动骨骼肌中年龄依赖性脂质组重塑，并通过调节膜流动性和内质网应激信号恶化肌肉质量和收缩性。
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.
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影响因子：
82.9
作者：
Erbay, Ebru;Babaev, Vladimir R.;Mayers, Jared R.;Makowski, Liza;Charles, Khanichi N.;Snitow, Melinda E.;Fazio, Sergio;Wiest, Michelle M.;Watkins, Steven M.;Linton, MacRae F.;Hotamisligil, Goekhan S.
通讯作者：
Hotamisligil, Goekhan S.
DOI：
10.1038/nrrheum.2017.60
发表时间：
2017-06
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
Dennison EM;Sayer AA;Cooper C
通讯作者：
Cooper C
影响因子：
5.5
作者：
Blondelle J;Ohno Y;Gache V;Guyot S;Storck S;Blanchard-Gutton N;Barthélémy I;Walmsley G;Rahier A;Gadin S;Maurer M;Guillaud L;Prola A;Ferry A;Aubin-Houzelstein G;Demarquoy J;Relaix F;Piercy RJ;Blot S;Kihara A;Tiret L;Pilot-Storck F
通讯作者：
Pilot-Storck F
影响因子：
4
作者：
Dupont, Jolan;Dedeyne, Lenore;Gielen, Evelien
通讯作者：
Gielen, Evelien
影响因子：
4.5
作者：
Devkota R;Svensk E;Ruiz M;Ståhlman M;Borén J;Pilon M
通讯作者：
Pilon M