Increased hepatic fatty acids uptake and oxidation by LRPPRC-driven oxidative phosphorylation reduces blood lipid levels

Frontiers in Physiology

卷:7

Mei-zhen Gong¹  Shi Lei¹  Di Wang²  Wei He³  Jun-lin Li³  Xin-yan Wang⁴  Ping Zhou⁴  Chi Wei⁴ 

[1] China Three Gorges University;

[2] Huashan Hospital North, Shanghai Medical School, Fudan University;

[3] Northwest University;

[4] People's Liberation Army Air Force General Hospital;

关键词: Fatty Acids;    Mitochondria;    Oxidative Phosphorylation;    Triglycerides;    LRPPRC;   

DOI  :  10.3389/fphys.2016.00270

来源: DOAJ

【 摘 要 】

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 complex activities were measured using specific assay kits. The uptake and oxidation of fatty acid by hepatocytes were assessed using 14C-palmitate. LRPPRC regulated the expression of genes encoded by mitochondrial genome but not those by nuclear genome involved in mitochondria biogenesis, oxidative phosphorylation, and lipid metabolism. Increased oxidative phosphorylation 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 oxidative phosphorylation could promote fatty acids uptake and oxidation by hepatocytes and reduce both hepatic and circulating triglyceride and cholesterol levels.

【 授权许可】

Unknown