The Impact of the Nrf2 Activator CDDO-Im on Hepatic Steatosis in High-fat Diet-induced Obese Mice
Objective:To investigate the effects of the Nrf2 activator CDDO-Im on hepatic steatosis in high-fat diet-induced obese mice.Methods:Thirty-three male C57BU6J mice were randomly divided into two groups:one group of 16 mice was fed a normal diet,while the other group of 17 mice was fed a high-fat diet to establish an obesity model.After successful modeling,the mice were randomly divided into four groups:normal diet solvent control group(Control ND group),normal diet Nrf2 activator group(Nrf2(+)ND group),high-fat diet solvent control group(Control HFD group),and high-fat diet Nrf2 activator group(Nrf2(+)HFD group).Nrf2 activator CDDO-Im and an equal volume of solvent were administered by gavage for 6 weeks,and the serum triglycerides(TG),total cholesterol(T-CHO),and low-density lipoprotein cholesterol(LDL-C)levels were measured in all groups.Hematoxylin-eosin(HE)staining was performed to observe the morphological changes in liver tissues.RT-qPCR was used to detect the mRNA expression levels of liver Nrf2 downstream antioxidant genes Nqo1,Ho1,and Gclc,while Western Blot was used to assess the protein expression levels of NQO1,HO-1,and GCLC in the liver.Results:Compared with that in the normal mice,body weight,TG,LDL-C and hepatic steatosis in obese mice increased(P＜0.05),while protein expression of GCLC decreased(P＜0.05).In obese mice,compared with that in the solvent control group,body weight,serum TG levels and hepatic steatosis of mice in the Nrf2 activator group reduced(P＜0.05),mRNA expression levels of Nqol and Gclc increased(P＜0.05),and protein expression levels of NQO1 and GCLC elevated(P＜0.05).Conclusion:The Nrf2 activator CDDO-Im can ameliorate hepatic steatosis in high-fat diet-induced obese mice,and its mechanism may be through upregulating the expression of antioxidant genes,thus inhibits hepatic oxidative stress.
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