Endoplasmic reticulum stress involved in the course of lipogenesis in fatty acids-induced hepatic steatosis.
OBJECTIVE
The aim of the present study is to elucidate whether endoplasmic reticulum stress involved in the course of lipogenesis in fatty acids induced hepatic steatosis and the potential effect of metformin on endoplasmic reticulum stress.


METHODS
HepG2 cells were exposed to different types of culture media. After incubation for 24 h, cells were harvested to evaluate cell survival rate and lipid level among different groups. Moreover, reverse transcriptase polymerase chain reaction and western blot for glucose-regulated protein-78 (GRP78), sterol response element-binding protein-1c (SREBP1c) and fatty acid synthase (FAS) were applied.


RESULTS
The levels of triglyceride (TG), mRNA of FAS, mRNA and protein of GRP78 and SREBP1c significantly increased in the free fatty acids (FFA)-induced hepatic steatosis group. Then, HepG2 cells with hepatic steatosis induced by FFA were treated by metformin, levels of TG, GRP78 mRNA, SREBP1c mRNA and FAS mRNA as well as GRP78 and SREBP1 protein levels were partially decreased but without significant differences.


CONCLUSIONS
Endoplasmic reticulum stress might be involved in lipogenesis in fatty acids-induced hepatic steatosis. Therefore, endoplasmic reticulum stress might serve as a novel target in the pathogenesis and therapy of non-alcoholic fatty liver disease.
Liu
Jiang
J
Department of Gastroenterology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Jin
Xi
X
Yu
Chao-Hui
CH
Chen
Shao-Hua
SH
Li
Wei-Ping
WP
Li
You-Ming
YM
D015153:Blotting, Western; D002470:Cell Survival; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005227:Fatty Acids / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005234:Fatty Liver / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D066298:In Vitro Techniques; D050155:Lipogenesis / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D000091342:Endoplasmic Reticulum Chaperone BiP; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D018840:HSP70 Heat-Shock Proteins; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D007004:Hypoglycemic Agents; D008565:Membrane Proteins; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; C018551:glucose-regulated proteins; D008687:Metformin