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Vitamin E impacts cholesterol metabolism in the intestine

By Jeremy Cockerill | February 17, 2010

Source: MedWire News

Vitamin E decreases endogenous cholesterol synthesis and apolipoprotein-AI-mediated cholesterol secretion in intestinal cells, French scientists have shown.

In a series of experiments using Caco-2 cells as a model of human enterocytes, they reveal the influence of tocopherols on cholesterol metabolism and elucidate the underlying molecular and genetic pathways.

Jean-François Landrier (University Aix-Marseille) and team evaluated the ability of α- and γ-tocopherol – the two forms of vitamin E found in the human diet – to modulate cholesterol metabolism in the intestine. These compounds are already known to impact cholesterol metabolism in the liver.

They cultivated Caco-2 monolayers then applied dietary concentrations of either α- or γ-tocopherol to the apical side. Both compounds resulted in a significant 20% decrease in cholesterol efflux with no impact on cholesterol uptake.

Further experiments revealed that application of α- and γ-tocopherol decreased de novo cholesterol synthesis by 16% and 63%, respectively.

To study the molecular mechanisms underlying these effects, the researchers performed microarray experiments. These revealed that tocopherols diminish transcription of between one-third and one-half of genes involved in the cholesterol synthesis pathway.

Further, they showed that tocopherols decrease intracellular oxysterol levels via downregulation of the enzyme CYP27A1, an effect that was correlated with the decrease in cholesterol synthesis.

Finally, they demonstrated that tocopherols significantly reduce ATP-binding cassette mRNA, an effect mediated by CYP27A1, oxysterols, and the liver X receptor.

Landrier and co-authors say their study shows for the first time that tocopherols inhibit the de novo synthesis of cholesterol within human intestinal cells and also have non-antioxidant properties. These findings could explain the inhibitory effect of tocopherols on blood high-density lipoprotein cholesterol, they suggest.

“Moreover, in pathophysiologic states, such as insulin resistance and diabetes, where the intestinal cholesterol synthesis is increased, the effect of tocopherols could limit, at least in part, cholesterol overproduction,” the authors conclude.

“These data reinforce the hypothesis that vitamin E strongly impacts cholesterol metabolism in the intestine.”