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

Nutr Res. 2015 Apr;35(4):337-45. doi: 10.1016/j.nutres.2015.02.008. Epub 2015 Feb 28.

Abstract

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.

Keywords: Abca1; Fas; Flavonoids; MicroRNAs; Obesity; Rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cholesterol / blood
  • Diet, High-Fat / adverse effects
  • Dose-Response Relationship, Drug
  • Dyslipidemias / drug therapy
  • Dyslipidemias / etiology
  • Female
  • Grape Seed Extract / pharmacology*
  • Lipid Metabolism / drug effects
  • Liver / drug effects*
  • Liver / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Obesity / drug therapy*
  • Proanthocyanidins / pharmacology*
  • Rats
  • Rats, Wistar
  • Triglycerides / blood

Substances

  • Grape Seed Extract
  • Grape Seed Proanthocyanidins
  • MIRN122 microRNA, rat
  • MIRN33 microRNA, rat
  • MicroRNAs
  • Proanthocyanidins
  • Triglycerides
  • Cholesterol