XBP-1重塑脂代谢延长线虫寿命,补充油酸也延寿
创作:FU 审核:mildbreeze 2019年08月10日
  • 线虫中,转录因子XBP-1s可活化内质网未折叠蛋白反应,延长寿命;
  • 在神经系统或肠道中表达XBP-1s可重塑线虫的脂质代谢,通过活化溶酶体脂肪酶和Δ9去饱和酶FAT-6,来降低甘油三酯水平、增加油酸(OA,一种单不饱和脂肪酸)水平,延长线虫寿命;
  • OA补充剂可延长野生型线虫的寿命,但无法进一步延长表达XBP-1s的线虫(OA水平已经升高)的寿命;
  • OA补充剂可改善线虫的蛋白质稳态,保护线虫免受蛋白毒性的伤害。
主编推荐语
mildbreeze
内质网未折叠蛋白反应(UPRER)是一种细胞应激反应,可维持分泌途径的稳态、调节葡萄糖和脂质代谢、影响寿命。Cell Reports上发表的一项线虫研究表明,表达UPRER转录因子XBP-1s可影响线虫的脂质代谢,增加油酸水平,延长线虫寿命。给线虫通过食物补充油酸也有延寿作用,与改善蛋白质稳态有关。
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Cell Reports [IF:7.815]

XBP-1 Remodels Lipid Metabolism to Extend Longevity

XBP-1重塑脂质代谢以延长寿命

10.1016/j.celrep.2019.06.057

2019-07-16, Article

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The endoplasmic reticulum unfolded protein response (UPR) is a cellular stress response that maintains homeostasis within the secretory pathway, regulates glucose and lipid metabolism, and influences longevity. To ask whether this role in lifespan determination depends upon metabolic intermediaries, we metabotyped C. elegans expressing the active form of the UPR transcription factor XBP-1, XBP-1s, and found many metabolic changes. These included reduced levels of triglycerides and increased levels of oleic acid (OA), a monounsaturated fatty acid associated with lifespan extension in C. elegans. Here, we show that constitutive XBP-1s expression increases the activity of lysosomal lipases and upregulates transcription of the Δ9 desaturase FAT-6, which is required for the full lifespan extension induced by XBP-1s. Dietary OA supplementation increases the lifespan of wild-type, but not xbp-1s-expressing animals and enhances proteostasis. These results suggest that modulation of lipid metabolism by XBP-1s contributes to its downstream effects on protein homeostasis and longevity.

First Authors:
Soudabeh Imanikia,Ming Sheng

Correspondence Authors:
Rebecca C Taylor

All Authors:
Soudabeh Imanikia,Ming Sheng,Cecilia Castro,Julian L Griffin,Rebecca C Taylor

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