Effect of lipoic acid on the expression of nonalcoholic fatty liver disease-associated genes in the liver of rats fed a hypercaloric choline-deficient diet

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver pathologies. Molecular mechanisms of NAFLD pathogenesis are complex and still require further clarification. Thus, this study aimed to investigate the impact of lipoic acid (LA), widely used as an antioxidant, on the development of different links of NAFLD, including de novo lipogenesis, antioxidant and xenobiotic-metabolizing enzymes by gene expression analysis. The experiment was carried out on three groups of male Wistar rats received control diet, hypercaloric choline-deficient diet (HCCD) or HCCD with LA (HCCD+LA). In the liver of rats the expression of acetyl-CoA carboxylase 1 (Acaca), fatty acid synthase (Fasn), stearoyl-CoA desaturase (Scd) and transcriptional regulators sterol-regulatory element-binding protein SREBP (Srebf1), carbohydrate response element-binding protein ChREBP (Mlxipl), peroxisome proliferator-activated receptor alpha PPARα (Ppara), heme oxygenase-1 HO-1 (Hmox1) and nuclear erythroid 2-related factor 2 Nrf2 (Nrf2), cytochrome P450 1A1 CYP1A1 (CYP1A1) and aryl hydrocarbon receptor AhR (AhR), cytochrome P450 2E1 CYP2E1 (CYP2E1) genes were evaluated. Supplementation of HCCD with LA led to an even greater than in HCCD group decrease in Scd gene expression by 88% (p<0.05), as well as a marked suppression of Ppara and Mlxipl by 37% (p<0.05) and 27% (p<0.05), to an 80% (p<0.05) elevation of Hmox1 gene expression relative to the HCCD group, had no pronounced effect on CYP1A1 and AhR gene expression but resulted in a 38% (p<0.05) suppression of CYP2E1 expression compared with that slightly elevated by HCCD. In conclusion, the current study showed that LA reduces lipogenesis de novo, restores the expression of Hmox1 gene of the antioxidant enzyme HO-1, diminished by the HCCD diet, and decreases HCCD-induced level of the expression of CYP2E1 gene of CYP2E1 enzyme, a potential source of free radicals.