Effects of vitamin A (Retinoic Acid) on liver triglycerides and diacylglycerol acyltransferase2 (DGAT2) gene expression in high cholesterol diet- induced steatosis rat model

Abstract

Non-acholic fatty liver disease is the main hepatic manifestation of metabolic syndrome. It characterizes when macrovesicular steatosis find in ≥5% of liver cells in the absence of secondary triggering factors. The incidence of Non-alcoholic fatty liver disease (NAFLD) is increasing worldwide, however, to date no single effective treatment is available. In many studies, depending on the severity of the disease, serum level of retinoic acid was found to be low in NAFLD patients. Different therapeutic agents were studied but the effects of retinoic acid on NAFLD have not yet been well studied. This study was conducted to investigate the effects of retinoic acid on liver triglyceride level and Diacylglycerol acyltransferase 2 (DGAT2) gene expression in high cholesterol diet-induced steatosis rats. Forty male Sprague-Dawley rats were divided into five groups (n=8/group). Group A and B received normal diet while, group C, D and E fed high cholesterol diet (HCD) for the first four weeks to induce steatosis. For the second four weeks they received either a standard diet (Group A), a standard diet with retinoic acid (7.5mg/kg) subcutaneously twice weekly (Group B), a high cholesterol diet (Group C), high cholesterol diet and vehicle (Olive oil) (Group D), or a high cholesterol diet with retinoic acid (7.5mg/kg) subcutaneously twice weekly (Group E), respectively. At the end of the experiment, the rats were fasted overnight and euthanized with an overdose mixture of anesthesia. The liver tissue was collected, processed, and stored at -80°C for further biochemical and molecular studies. Liver triglyceride levels were determined using Bligh & Dyer method and the hepatic expression of the DGAT2 gene was quantified using Real-Time TaqMan qPCR. Retinoic acid-treated groups showed a reduced pattern in hepatic DGAT2 gene expression and liver triglyceride levels when compared with standard and high cholesterol diet groups. However, liver triglyceride levels and DGAT2 gene expression were not statistically significant (P>0.05). These findings suggest that retinoic acid administration might reduce the liver triglyceride level through its action on DGAT2 gene expression. However, further studies are required to confirm retinoic acid as a potential candidate for improving NAFLD.