Gene expression microarray analysis of the effects of grape anthocyanins in mice: a test of a hypothesis-generating paradigm

Abstract

The mechanism(s) through which fruits, vegetables and whole grains favorably affect health is not well established. Employing an anthocyanin-rich grape as a model, we examined the ability of an agnostic analytical approach employing gene expression microarrays, to generate novel testable hypotheses regarding the mechanisms of action of potentially healthful foods and food components. C57Bl/6 mice were divided into two groups and fed a proatherogenic diet with or without a semi-purified anthocyanin extract (70% anthocyanins) incorporated at a level of 0.1 mg/ml into the drinking water. After six weeks, compared to control mice, mice supplemented with anthocyanins tended to gain more weight and have increased adipose tissue mass, although these effects did not achieve statistical significance. Anthocyanin supplemented mice had significantly reduced relative liver weights and heart weights. Serum lipids and inflammatory cytokines were not different between the groups. Gene expression microarray analysis of the liver and skeletal muscle identified a number molecular pathways significantly affected by anthocyanin treatment. Two distinct clusters emerged. The first cluster included down-regulated pathways in both muscle and liver involving cellular defense while the second included hepatic genes involved in energy metabolism. From these data three hypotheses were developed for future investigation.

Nutrigenomic analysis of the protective effects of bilberry anthocyanin-rich extract in apo E-deficient mice

“…Using C57BL/6 J mice fed with an atherogenic diet, Lefevre et al demonstrated that supplementation with an anthocyanin-rich extract from grapes significantly affected cholesterol biosynthesis and fatty acid b-oxidation, both pathways being regulated by nuclear receptors such as liver x-receptor (LXR) or peroxisome proliferator-activated receptors (PPARs) [15]. The authors suggested that grape anthocyanins could alter lipid metabolism in the liver through the modulation of the activities of these receptors.…”

“…Global genomic approach, using microarray technology, allows studying the effects of foods or food-derived bioactive components at a genome-wide level. Up to now, only two studies using microarrays have reported effects of anthocyanins or anthocyanin-rich extracts on global gene expression [14,15]. A bilberry extract has been found to attenuate the expression of inflammation and cell defencerelated genes in cultured mouse macrophages [14].…”

“…A bilberry extract has been found to attenuate the expression of inflammation and cell defencerelated genes in cultured mouse macrophages [14]. Moreover, Lefevre et al reported that a 6-week grape anthocyanin supplementation in C57BL/6 J mice modulated the expression of genes involved in the inflammatory response in both liver and skeletal muscle [15]. No similar genomic study has so far been carried out on the anti-atherosclerotic properties of anthocyanins or anthocyanin-rich extract.…”

Wild blueberries attenuate risk factors of the metabolic syndrome

“…Feeding anthocyanin-rich extracts to mice on a high-fat diet resulted in decreased TNF-␣ expression [19,20], and the same outcome was observed in mice adipocytes when 4% whole blueberry powder was added for 8 weeks to a high-fat diet [21]. In hypercholesterolemic humans, decreased levels of serum CRP were measured in after 24 weeks of consumption of a purified anthocyanin mixture (320 mg twice a day) [22].…”

Effects of Thai black sticky rice extract on oxidative stress and lipid metabolism gene expression in HepG2 cells

“…Since the present study showed that ARE induces the expression of LDLR and PPARg genes, these particular genes may regulate energy metabolism in the HepG2 cells. According to microarray analysis, gene expression patterns of liver and skeletal muscles were significantly affected by treatment with anthocyanins (Lefevre et al, 2008). In particular, the first set discovered included down-regulated pathways in both muscle and liver involved in cellular defense (inflammatory response genes and oxidative stress genes), whereas another set included hepatic genes involved in energy metabolism in the liver, with major metabolic pathways down-regulated such as the TCA cycle, fatty acid β-oxidation, and cholesterol biosynthesis.…”