Naltrexone changes the expression of lipid metabolism-related proteins in the endoplasmic reticulum stress induced hepatic steatosis in mice.
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/BL6 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 GRP78, IRE1α, PERK and ATF6 gene expression and steatosis significantly reduced in naltrexone treated animals. Naltrexone alleviated the gene and protein expression of SREBP1c. Expression of ACAT1, apolipoprotein B (ApoB) and PPARα 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.
Cellular& Molecular Research Center, Qom University of Medical Sciences, Qom, Iran.
Azam
A
Moslehi
Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Fatemeh
F
Nabavizadeh
Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran.|Physiology Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran.
Ali
A
Zekri
Physiology Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran.|Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.
Fatemeh
F
Amiri
D051702:Activating Transcription Factor 6 / Q000235:genetics; D000818:Animals; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000235:genetics; D004722:Endoribonucleases / Q000235:genetics; D005234:Fatty Liver / Q000378:metabolism / Q000517:prevention & control*; D015870:Gene Expression / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects*; D008810:Mice, Inbred C57BL; D009271:Naltrexone / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014415:Tunicamycin / Q000494:pharmacology; D019892:eIF-2 Kinase / Q000378:metabolism
D051702:Activating Transcription Factor 6; D000091342:Endoplasmic Reticulum Chaperone BiP; D004722:Endoribonucleases; D009271:Naltrexone; D017346:Protein Serine-Threonine Kinases; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D014415:Tunicamycin; D019892:eIF-2 Kinase; C497112:Atf6 protein, mouse; C000717248:Hspa5 protein, mouse; C497388:Srebf1 protein, mouse; C510185:Ern1 protein, mouse
endoplasmic reticulum stress; lipoprotein; liver; opioids; steatosis