N-油酰(基)甘氨酸与油酸对线粒体UCP1非依赖产热的影响  

Effects of N-Oleoylglycine and Oleate on Mitochondrial UCP1-independent Thermogenesis

作　　者：高芸 徐美雪 于太永[1] 庞卫军[1] 杨公社[1] GAO Yun;XU Mei-Xue;YU Tai-Yong;PANG Wei-Jun;YANG Gong-She(Laboratory of Animal Fat Deposition and Muscle Development,Northwest A&F University,Yangling 712100,Shaanxi,China)

机构地区：[1]西北农林科技大学动物科技学院动物脂肪沉积与肌肉发育实验室,陕西杨凌712100

出　　处：《中国生物化学与分子生物学报》2021年第11期1482-1488,共7页Chinese Journal of Biochemistry and Molecular Biology

基　　金：陕西省重点研发计划项目(No.2018ZDCXL-NY-02-05);国家生猪产业技术体系项目(No.CARS-35)资助。

摘　　要：除了UCP1依赖性的脂肪产热途径外,UCP1非依赖产热途径也可增加脂肪消耗,进而抵抗肥胖。有研究提出N-脂酰(基)氨基酸(N-acyl amino acids,NAAs)可以作为线粒体产热的新型内源性解耦联剂来介导脂肪中的UCP1非依赖产热。本文利用不表达UCP1的C2C12小鼠成纤维细胞作为UCP1缺失细胞模型,选取高脂小鼠血浆中含量极高的一种NAA—N-油酰(基)甘氨酸(N-oleoylglycine),对比与其结构对应的普通脂肪酸—油酸(oleate),探究N-油酰(基)甘氨酸相比于油酸诱导线粒体产热的效果与机制。研究发现,添加60μmol/L的油酸可以诱导线粒体的氧化磷酸化蛋白质的表达,上调线粒体产热相关基因COX8b、DIO2和UCP3等的表达(P<0.05)。而添加60μmol/L的N-油酰(基)甘氨酸损伤了细胞线粒体生成和氧化磷酸化蛋白质的表达,显著降低产热基因PGC1a,COX8b、COX2、DIO2、UQCRFS1和UCP3的表达(P<0.01),诱导细胞线粒体自由基(reactive oxygen species,ROS)的产生,增强了细胞的氧化应激。本文的研究发现,在60μmol/L的添加浓度下,油酸可以诱导细胞的UCP1非依赖产热,而N-油酰(基)甘氨酸不能,反而会造成细胞的氧化应激。Besides UCP1-dependent thermogenesis pathways,UCP1-independent thermogenesis pathways also could increase heat production in adipose tissue to combat obesity.N-Acyl amino acids(NAAs)have been suggested as novel endogenous uncouplers to induce mitochondria UCP1-independent thermogenesis in adipose tissue.Here,we use mouse skeletal muscle C2 C12 cells which lack of UCP1 as UCP1 negative cell models.Comparing with its corresponding common fatty acid—oleate,one of the NAAs—N-Oleoylglycine(NOGly),which is highly expressed in the plasma of HFD mice,is selected to study their effects and mechanisms on mitochondrial thermogenesis.We found that 60μmol/L oleate could induce mitochondrial oxidative phosphorylation protein levels,as well as increase mitochondria thermogenesis-related genes(COX8b,DIO2,UCP3)expression(P<0.05).However,60μmol/L NOGly damaged the production and oxidative phosphorylation of mitochondria,significantly down-regulated expression of thermogenic genes(PGC1a,COX8b,COX2,DIO2,UQCRFS1 and UCP3)(P<0.01),induced the production of reactive oxygen species(ROS)in the mitochondria,and enhanced the oxidative stress in cells.Our study found that oleate can induce UCP1-independent thermogenesis under 60μmol/L addition dose,whereas NOGly does not due to the induction of oxidative stress in cells.

关 键 词：脂肪酸 线粒体 UCP1非依赖产热 C2C12小鼠成纤维细胞 

分 类 号：Q591[生物学—生物化学]