The role of endoplasmic reticulum stress in the formation of fatty liver in high-fat diet fed mice
10.3760/cma.j.issn.1008-1372.2017.10.006
- VernacularTitle:内质网应激在高脂饲养小鼠脂肪肝形成中的作用
- Author:
Ni QIU
1
;
510095 广州,广州医科大学附属肿瘤医院乳腺外科
;
Xuemei WEI
;
Xiaomei LI
;
Yan XIONG
Author Information
1. 511436 广州,广州医科大学药学院,广州蛇毒研究所;510095 广州,广州医科大学附属肿瘤医院乳腺外科
- Keywords:
Endoplasmic reticulum stress;
High-fat diet;
Fatty liver;
De novo lipid synthesis
- From:
Journal of Chinese Physician
2017;19(10):1474-1478
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the influence of endoplasmic reticulum stress on fatty liver in mice feeding with high-fat diet.Methods The 8-week-old male C57BL/6J mice were randomly divided into two groups:high-fat diet group (with 60％ calories by high saturated fatty acid) and control group (with chow diet),both groups had been fed for 16 weeks.H&E-staining and Sudan Ⅳ-staining reflected lipid deposition in liver.The levels of 78-kDa glucose-regulated protein (GRP78),protein kinase R-like endoplasmic reticulum kinase (PERK),phosphorylated α subunit of eukaryotic initiation factor 2 (p-eIF1 α),C/EBP homologous protein (CHOP),steroid regulated element binding proteins 1 (SREBP-1),and fatty acid synthetase (FAS) protein were determined by Western blot to reflect the endoplasmic reticulum stress and lipid synthesis.Results In liver of high fat diet (HFD) group,H&E staining showed that the cytoplasm of hepatocytes were filled with vacuoles,Sudan Ⅳ staining also displayed that many different sizes of red lipid drops exist in hepatocytes.Compared to the liver of control group,high-fat diet induced endoplasmic reticulum stress and elevated lipid synthesis,as evidenced by increases in the level of peroxisome proliferator-activated receptor alpha (PPARα) mRNA expression,and the protein levels of GRP78,PERK,phosphorylated eIF2α,CHOP were also significantly increased.In primary normal hepatocytes incubated with exogenous oleic acid intervention for 24-72 hours,the expression of GRP78,PERK,phosphorylated eIF2α,CHOP protein levels,and the expression of SREBP-1 and FAS protein were significantly increased in dose-dependent manner.Conclusions Feeding with high-fat diet led to accumulation of lipid deposition in liver and fatty liver,the underlying mechanisms might be related to induction of endoplasmic reticulum stress.
