Effects Of Metformin Versus Dietary Intervention On The Expressions Of Adiponectin And Its Receptors In The Liver Of NAFLD Rats

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is a liver diseasecorrelated with obesity deficient in specific therapy. Adiponectin is an adipokine thathave anti-inflammtion、antidiabetic and anti-atherosclerosis properties. We aim toinvestigate the role of adiponectin in the pathogenesis of NAFLD and the therapeuticeffects of dietary intervention or metformin treatment on the NAFLD.Methods: Forty-eight male SD rats were randomized to six groups, including twonormal control groups (NC1,8thweek and NC2,16thweek), two HFD groups (HFD1,8thweek and HFD2,16thweek), one dietary intervention group (DIET group) and onemetformin treatment group (HFD+M group). The serum adiponectin concentrationand biochemical assays were detected through enzyme-linked immunosorbent assay(ELISA).The protein or mRNA expressions of hepatic adiponectin and its receptorswere detected through western blotting and immunohistochemistry or RT-PCRrespectively.Results: The NAFLD activity score (NAS) in HFD group rats from3.7±0.52(8thweek) to6.57±0.79(16thweek)(P<0.001) reflected the progress of NAFLD histology.NAS of16thweek was diagnosed as having NASH. The immunohistochemmicalscores of adiponectin and its receptors correlated with grade of inflammation, fatpercent, ballooning degeneration (P<0.001, respectively) negatively. In contrast to theHFD2group, after dietary intervention or metformin treatment, the samples both hadalleviation in the steatosis and ballooning degeneration. It is dietary intervention(0.86±0.38vs2.14±0.38, P<0.001) but not metformin treatment (2±0.63vs2.14±0.38,P>0.05) alleviated the inflammation as compared to HFD2group. Protein and mRNAexpressions of adiponectin and its receptors in liver tissues decreased in HFD fedgroups, concomitantly with elevated liver enzymes, dyslipidemia and insulinresistance. Dietary intervention increased the protein and gene levels of adiponectin and its receptors, concomitantly with ameliorating the biochemical assays.Nevertheless, metformin did not work in altering the expressions of adiponectinsystem (adiponectin and its receptors) or the biochemical assays and caused damageon the liver function. Metformin worsened the level of ALT compared to HFD2grouprats (P<0.05).Conclusions: The rat NAFLD model could be built successfully by feeding high fatdiet. Adiponectin may play a role in the pathogenesis of NAFLD, especially fromsteatosis to NASH. Dietary intervention could ameliorate the hepatic steatosis,ballooning degeneration and inflammation by up-regulatting the expressions ofadiponectin and its receptors of the liver tissue. Metformin had no impact on theexpressions of adiponectin and its receptors, and this could explain the noamelioration of hepatic inflammation. Dietary intervention must be the cornerstone inthe treatment of NASH doubtlessly.