Long-term supplementation with a low dose of proanthocyanidins normalized liver miR-33a and miR-122 levels in high-fat diet-induced obese rats.

Deregulation of miR-33 and miR-122, as major regulators of lipid metabolism in liver, has been related to obesity and metabolic syndrome. Proanthocyanidins repress these microRNAs in healthy animals. Hence, we hypothesized that long-term consumption of dietary proanthocyanidins can normalize the expression of miR-33a and miR-122. Therefore, the objective of this work was to determine whether the long-term consumption of proanthocyanidins could effectively normalize the expression of miR-33a and miR-122 in rats made obese by a high-fat diet and to determine the effective dose. Rats were maintained on the high-fat diet with or without supplementation with a grape seed proanthocyanidin extract at low, medium, or high dose in relation to human consumption. Results show that 3 weeks of supplementation with grape seed proanthocyanidin extract normalized the overexpression of miR-33a and miR-122 in obese rats' liver for all doses studied, with no dose-dependent outcome, and also reduced the levels of plasma and liver lipids in a dose-dependent manner. In conclusion, a low sustained dose of proanthocyanidins, lower than the estimated mean intake for a European population, is enough to normalize miR-33a and miR-122 levels in the livers of obese rats. Therefore, a proanthocyanidin-rich diet during obesity can improve some of the metabolic syndrome symptoms at least at the molecular level.