The role of ADIPOQ methylation in curcumin-administrated experimental nonalcoholic fatty liver disease.

OBJECTIVE: To investigate the role of adiponectin precursor (ADIPOQ) DNA methylation in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and the effect of curcumin on the development of NAFLD using rat models.

METHODS: Male Sprague-Dawley rats were divided into the control, NAFLD and curcumin-treated groups. The genetic and epigenetic features of each rat were measured and recorded. Real-time polymerase chain reaction (PCR), Western blot and bisulfite sequencing PCR (BSP) were used to quantify the ADIPOQ mRNA and protein expressions, and DNA methylation status, respectively.

RESULTS: Serum levels of alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC) and fasting blood glucose in the NAFLD group were significantly increased compared with the control group. The genetic and epigenetic features were reversed after curcumin treatment. The ADIPOQ mRNA and protein expressions in the livers of the NAFLD rats was lower compared with the control and the curcumin-treated groups. ADIPOQ methylation rate in the NAFLD group was significantly higher than in the control group, which was declined slightly following curcumin treatment. A negative correlation was found between the degrees of DNA methylation and ADIPOQ mRNA expression. ALT, TC, TG and homeostatic model assessment insulin resistance index had a positive correlation with ADIPOQ DNA methylation, showing that curcumin might affect the gene expression involved in lipid and glucose metabolism by influencing ADIPOQ DNA methylation modifications, which contributed to alleviation of NAFLD.

CONCLUSION: Altering the DNA methylation of ADIPOQ is one of the mechanisms by which curcumin executes its hepatoprotective function in NAFLD.