Anthocyanin-rich bilberry extract and resveratrol as protectors against mitochondrial dysfunction induced by mixed micelles in Caco-2 intestinal epithelial cells.

Abstract

Healthy and efficient mitochondria have a critical role in maintaining intestinal cell function and preventing pathological conditions. The influence of dietary fat, and possible protection by dietary polyphenols, on mitochondrial function in intestinal epithelial cells, however, is relatively unexplored. In this study we aimed to test the influence of dietary fat on mitochondrial content and function in intestinal epithelial cells, possible protection by berry anthocyanins and resveratrol, and the mechanisms involved. Caco-2 intestinal epithelial cells were exposed to 0.4 or 0.1 mM mixed micelles (MM) composed of lipids and bile acid in the absence or presence of 20 µM resveratrol or anthocyanins in an anthocyanin-rich bilberry extract (ARBE), added 5h or 2h, respectively prior to MM. After 24 h, indices of mitochondrial content and function were measured. MM exposure decreased measures of mitochondrial function (membrane potential and respiratory functions), as well as citrate synthase activity and expression of mRNA for mtDNA-encoded respiratory complex proteins (MTND1, MTCYB, MTCO1, MTATP) (P<0.05). Treatment with resveratrol increased mitochondrial content and transcription of genes involved in mitochondrial biogenesis (PGC-1α, NRF-1, TFAM) (P<0.05) but did not significantly protect against MM-induced declines in mitochondrial functions. Conversely, ARBE protected against decreases in parameters of mitochondrial function (P<0.05) but had little effect on indices of mitochondrial content and biogenesis. Neither resveratrol nor ARBE protected against the MM-induced decrease in expression of mtDNA-encoded mRNAs. The results support that MM, representing emulsified dietary fat, produce mitochondrial dysfunction in intestinal epithelial cells, and that berry anthocyanins, unlike resveratrol, can protect intestinal cell mitochondria by a direct mechanism not involving mitochondrial biogenesis.