Effects of Moderate Ethanol Consumption on Lipid Metabolism and Inflammation Through Regulation of Gene Expression in Rats

Wistar rats exposed for 3 months to a 20% ethanol intermittent-access voluntary drinking paradigm displayed a reduction in epididymal fat, blood glucose and non-HDL and total cholesterol. These effects were accompanied by decreased expression of Hmgcr, Srebp-2, Cox-2 and RelA, indicating downregulation of genes involved in cholesterol synthesis and inflammation. Abstract Aims Epidemiological studies and experimental data from rodent models have reported a non-linear relationship between consumption of alcohol and cardiovascular disease (CVD) risk that suggests that light-to-moderate drinking as opposed to excessive consumption may provide some cardiovascular benefits. The present study examined potential mechanisms by which moderate alcohol consumption may provide a protective effect against CVD. Short summary Wistar rats exposed for 3 months to a 20% ethanol intermittent-access voluntary drinking paradigm displayed a reduction in epididymal fat, blood glucose and non-HDL and total cholesterol. These effects were accompanied by decreased expression of Hmgcr, Srebp-2, Cox-2 and RelA, indicating downregulation of genes involved in cholesterol synthesis and inflammation. Methods Twenty-four male Wistar rats voluntarily consumed a 20% v/v ethanol solution on alternate days for 13 weeks (ethanol-treated) or were given access to water alone (non-ethanol-exposed control). Results There was no difference in body weight gain between the two groups, however, epididymal fat weight was lower in ethanol-fed rats (P = 0.030). Blood glucose, total cholesterol, non-high-density lipoprotein (HDL) and oxidized low-density lipoprotein (LDL) levels were lower in the ethanol group compared to controls (P < 0.05). There was a significant reduction in the expression of hydroxymethylglutaryl-coenzyme A reductase and sterol regulatory element-binding protein-2 in ethanol-treated rats (P < 0.05), suggesting that ethanol may have lowered cholesterol levels via downregulation of genes involved in cholesterol synthesis. Paraoxonase-1, which is associated with inhibition of LDL cholesterol oxidation, was upregulated in the ethanol group (P = 0.029). Ethanol-treated rats exhibited significantly lower levels of high-mobility box group protein 1 (P 0.05). Cyclooxygenase-2 and RelA gene expression were significantly lower in ethanol-treated rats (P < 0.05), indicating possible anti-inflammatory effects. Conclusions These findings suggest that moderate ethanol consumption may potentially contribute to improved cardiovascular outcomes by reducing body fat, improving blood cholesterol and blood glucose, and modulation of gene expression involved in inflammation and/or cholesterol synthesis.