Lei Shi, Sun Run-Zhu, Wang Di, Gong Mei-Zhen, Su Xiang-Ping, Yi Fei, Peng Zheng-Wu
College of Biological and Pharmaceutical Sciences, China Three Gorges University Yichang, China.
Department of Psychiatry, Xijing Hospital, Fourth Military Medical University Xi'an, China.
Front Physiol. 2016 Jul 12;7:270. doi: 10.3389/fphys.2016.00270. eCollection 2016.
Hyperlipidemia is one of the major risk factors of atherosclerosis and other cardiovascular diseases. This study aimed to investigate the impact of leucine rich pentatricopeptide repeat containing protein (LRPPRC)-driven hepatic oxidative phoshorylation on blood lipid levels. The hepatic LRPPRC level was modulated by liver-specific transgenic or adeno-associated virus 8 carried shRNA targeting Lrpprc (aav-shLrpprc). Mice were fed with a high fat diet to induce obesity. Gene expression was analyzed by quantitative real-time PCR and / or western blot. The hepatic ATP level, hepatic and serum lipids contents, and mitochondria oxidative phosphorylation (OxPhos) complex activities were measured using specific assay kits. The uptake and oxidation of fatty acid by hepatocytes were assessed using (14)C-palmitate. LRPPRC regulated the expression of genes encoded by mitochondrial genome but not those by nuclear genome involved in mitochondria biogenesis, OxPhos, and lipid metabolism. Increased OxPhos in liver mediated by LRPPRC resulted in the increase of hepatic ATP level. Lrpprc promoted palmitate uptake and oxidation by hypatocytes. The hepatic and serum triglyceride and total cholesterol levels were inversely associated with the hepatic LRPPRC level. These data demonstrated that LRPPRC-driven hepatic OxPhos could promote fatty acids uptake and oxidation by hepatocytes and reduce both hepatic and circulating triglyceride and cholesterol levels.
高脂血症是动脉粥样硬化和其他心血管疾病的主要危险因素之一。本研究旨在探讨富含亮氨酸的五肽重复序列蛋白（LRPPRC）驱动的肝脏氧化磷酸化对血脂水平的影响。通过肝脏特异性转基因或携带靶向Lrpprc的短发夹RNA的腺相关病毒8（aav-shLrpprc）来调节肝脏LRPPRC水平。给小鼠喂食高脂饮食以诱导肥胖。通过定量实时PCR和/或蛋白质印迹分析基因表达。使用特定的检测试剂盒测量肝脏ATP水平、肝脏和血清脂质含量以及线粒体氧化磷酸化（OxPhos）复合物活性。使用（14）C-棕榈酸评估肝细胞对脂肪酸的摄取和氧化。LRPPRC调节线粒体基因组编码的基因表达，但不调节参与线粒体生物发生、氧化磷酸化和脂质代谢的核基因组编码的基因表达。由LRPPRC介导的肝脏氧化磷酸化增加导致肝脏ATP水平升高。Lrpprc促进肝细胞对棕榈酸的摄取和氧化。肝脏和血清甘油三酯及总胆固醇水平与肝脏LRPPRC水平呈负相关。这些数据表明，LRPPRC驱动的肝脏氧化磷酸化可促进肝细胞对脂肪酸的摄取和氧化，并降低肝脏和循环中的甘油三酯及胆固醇水平。
