Naltrexone changes the expression of lipid metabolism-relatedproteins in the endoplasmic reticulum stress induced hepatic steatosis in mice

Azam Moslehi,1,* Fatemeh nabavizadeh ,2 Ali zekri,3 Fatemeh amiri,4

1. Qom University of Medical Sciences, Qom
2. Tehran University of Medical Sciences, Tehran
3. Iran University of Medical Sciences,Tehran
4. Institute for Research and Education in Transfusion Medicine, Tehran

Abstract

Introduction

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 cirrhosis. opioids are involved in triglyceride and cholesterol dysregulation. previously, we showed naltrexone attenuated 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.

Methods

C57/bl6 mice received saline, dmso and naltrexone as control groups. in a fourth group, er stress was induced by 2 mg/kg tunicamycin (tm) injection and in the last group; naltrexone was given 30 minutes before tm administration (tm plus naltrexone group). histopathological evaluation, real-time rt-pcr and western blot analysis were performed.

Results

We found that in the er stress group, grp78, ire1α, perk and atf6 (as er stress markers) gene expressions increased, oil red o staining showed lipid droplets accumulation in the hepatocytes. srbp1-c expression was upregulated and in contrast, pparα, apolipiprotein b and acetyltransferase (acat1) expression downregulated. our findings demonstrated that after naltrexone treatment grp78, ire1α, atf6 and perk gene expression decreased. mrna and protein expressions of srebp1c, a lipogenic factor, decreased and pparα, a lipolysis transcription factor, increased. furthermore, gene expression of apolipiprotein b and acat1 was upregulated in the tm plus naltrexone group. steatosis reduced after naltrexone treatment.

Conclusion

This study demonstrated that naltrexone alleviate the expression of grp78, ire1α, atf6, perk and srebp1c and increase acat1, apob and pparα expressions. also, improve liver steatosis.

Keywords

Liver, steatosis, er stress, naltrexone