The therapeutic effects of berberine plus sitagliptin in a rat model of fatty liver disease

Objective(s): Fatty liver disease (FLD) is a disorder related to accumulation of excess fat within the hepatocytes. In this study, the effects of berberine, a natural compound, and sitagliptin as a DPP-4 inhibitor, were observed in a rat model of FLD. Materials and Methods: Forty male rats were divided into five groups (n=6) including the control group (normal food and water), high-fat group (high-fat diet (HF) for 6 weeks), berberine group (HF with oral administration of berberine at 150 mg/kg for 6 weeks), sitagliptin group (HF with oral administration of sitagliptin at 10 mg/kg for 6 weeks), and berberine/ sitagliptin group (HF diet within combination with oral administration of berberine 75 mg/kg and sitagliptin 5 mg/kg for 6 weeks). Animals were examined for weight gain, serum and hepatic biochemical parameters, tissue histology, expression of glucose transporter type 4 (GLUT4) mRNA, and protein expression of Adiponectin receptor2 (AdipoR2) and extracellular signal-regulated kinase (ERK) and phoERK. Results: The results showed that ALT, AST, lipid profile, insulin, glucose, MDA, and TNF-α were significantly improved in high-fat rats treated with berberine/ sitagliptin compared with HF and sitagliptin, and berberine alone groups. SOD and adiponectin levels in berberine/ sitagliptin group were also significantly increased compared with the other groups. Immunoblot analysis showed that the expression of pho-ERK/ERK was significantly decreased and expression of AdipoR2 significantly increased in the berberine/ sitagliptin group compared with other groups. Conclusion: Co-administration of berberine and sitagliptin is an effective therapeutic regimen for conditions associated with hyperlipidemia.