Dietary cholesterol induces hepatic inflammation and blunts mitochondrial function in the liver of high-fat-fed mice

卷:27

Li, Songpei ; Zeng, Xiao-Yi ; Zhou, Xiu ; Wang, Hao ; Ja, Eunjung ; Robinson, Stephen R. ; Xu, Aimin ; Ye, Ji-Ming

RMIT Univ

关键词: Dietary cholesterol;    High fat diet;    Inflammation;    Mitochondrial function;    Nonalcoholic fatty liver disease;   

DOI  :  10.1016/j.jnutbio.2015.08.021

学科分类：食品科学和技术

【 摘 要 】

The present study investigated the role of dietary cholesterol and fat in the development of nonalcoholic fatty liver disease, a common liver disease in metabolic disorders. Mice were fed a diet of regular chow (CH), chow supplemented with 0.2% w/w cholesterol (CHC), high fat (HF, 45 kcal%) or HF with cholesterol (HFC) for 17 weeks. While both HF and HFC groups displayed hepatic steatosis and metabolic syndrome, only HFC group developed the phenotype of liver injury, as indicated by an increase in plasma level of alanine transaminase (ALT, by 50-80%). There were similar to 2-fold increases in mRNA expression of tumor necrosis factor et, interleukin 113 and monocyte chemotactic protein 1 in the liver of HFC-fed mice (vs. HF) but no endoplasmic reticulum stress or oxidative stress was observed. Furthermore, cholesterol suppressed HF-induced increase of peroxisome proliferator-activated receptor gamma coactivator lot and mitochondrial transcription factor A expression and blunted fatty acid oxidation. Interestingly, after switching HFC to HF diet for 5 weeks, the increases in plasma ALT and liver inflammatory markers were abolished but the blunted of mitochondrial function remained. These findings suggest that cholesterol plays a critical role in the conversion of a simple fatty liver toward nonalcoholic steatohepatitis possibly by activation of inflammatory pathways together with retarded mitochondria( function. (C) 2015 Elsevier Inc. All rights reserved.