Vitamin A Prevents High Fat Diet-Induced ACF Development and Modifies the Pattern of Expression of Peroxisome Proliferator and Retinoic Acid Receptor m-RNA

Abstract

Some dietary compounds, among them fats, are modulators of colon cancer risk. This study reports the modulating effects of n-6, with or without vitamin A, on promotion of colon preneoplasic lesions induced by 1,2-dimethylhydrazine (DMH) and on the expression of nuclear receptors (PPARγ, RXRα, and RARβ). One group of male Fisher rats was fed a basic diet (5% safflower oil) and two groups were fed a high-fat diet (HFD, 25% safflower oil). Of these, one was supplemented with 200 IU vitamin A for 5 mo. The safflower oil contained polyunsaturated fatty acids, mainly linoleic acid (73%). The data showed an increasing effect of safflower oil-enriched diet on aberrant crypt foci occurrence and multiplicity. This effect was impaired by vitamin A supplementation. In addition, an HFD-related up-regulation of PPARγ and a concomitant down-regulation of RARβ mRNA expression were observed with or without chemical initiation and were prevented by vitamin A. Moreover, when treated with DMH, HFD rats exhibited a dramatically decreased expression of RXRα mRNA (-49%). It was hypothesized that HFD, leading to hyperexpression of PPARγ, would produce an alteration of retinoic acid signaling and, in this way, create a background modulating colon cancer risk.