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Naltrexone changes the expression of lipid metabolism‐related proteins in the endoplasmic reticulum stress induced hepatic steatosis in mice
Author(s) -
Moslehi Azam,
Nabavizadeh Fatemeh,
Zekri Ali,
Amiri Fatemeh
Publication year - 2017
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12695
Subject(s) - steatosis , naltrexone , endocrinology , medicine , unfolded protein response , nonalcoholic fatty liver disease , fatty liver , endoplasmic reticulum , atf6 , triglyceride , chemistry , cholesterol , biochemistry , opioid , disease , receptor
Summary Endoplasmic reticulum ( ER ) stress is closely associated with several chronic diseases such as obesity, atherosclerosis, type 2 diabetes, and hepatic steatosis. Steatosis in hepatocytes may also lead to disorders such as nonalcoholic fatty liver disease ( NAFLD ) and nonalcoholic steatohepatitis ( NASH ), fibrosis, and possibly cirrhosis. Opioid peptides are involved in triglyceride and cholesterol dysregulation. Naltrexone also attenuates ER stress induced hepatic steatosis in mice. In this study, we evaluated the effects of naltrexone on the expression of lipid metabolism‐related nuclear factors and enzymes in the ER stress induced hepatic steatosis. C57/ BL 6 mice received saline, DMSO and naltrexone as control groups. In a fourth group, ER stress was induced by tunicamycin ( TM ) injection and in the last group, naltrexone was given before TM administration. Histopathological evaluations, real‐time RT ‐ PCR and western blot were performed. We found that GRP 78, IRE 1α, PERK and ATF 6 gene expression and steatosis significantly reduced in naltrexone treated animals. Naltrexone alleviated the gene and protein expression of SREBP 1c. Expression of ACAT 1, apolipoprotein B (ApoB) and PPAR α also increased after naltrexone treatment. In conclusion, this study, for the first time, shows that naltrexone has a considerable role in attenuation of ER stress‐induced liver injury.