Fatty acid synthase methylation levels in adipose tissue: effects of an obesogenic diet and phenol compounds

DNA methylation is an epigenetic mechanism that can inhibit gene transcription. The aim of this study was to assess changes induced by an obesogenic diet in the methylation profile of genes involved in adipose tissue triacylglycerol metabolism, and to determine whether this methylation pattern can be altered by resveratrol and pterostilbene. Rats were divided into four groups. The control group was fed a commercial standard diet, and the other three groups were fed a commercial high-fat, high-sucrose diet (6 weeks): the high-fat, high-sucrose group, the resveratrol-treated group (RSV; 30 mg/kg/day), and the pterostilbene-treated group (PT; 30 mg/kg/day). Gene expression was measured by RT-PCR and gene methylation by pyrosequencing. The obesogenic diet induced a significant increase in adipose tissue weight. Resveratrol and pterostilbene partially prevented this effect. Methylation pattern of ppnla2 and pparg genes was similar among the experimental groups. In fasn, significant hypomethylation in -90-bp position and significant hypermethylation in -62-bp position were induced by obesogenic feeding. Only pterostilbene reversed the changes induced by the obesogenic diet in fasn methylation pattern. By contrast, the addition of resveratrol to the diet did not induce changes. Both phenolic compounds averted fasn up-regulation. These results demonstrate that the up-regulation of fasn gene induced by an obesogenic feeding, based on a high-fat, high-sucrose diet, is related to hypomethylation of this gene in position -90 bp. Under our experimental conditions, both molecules prevent fasn up-regulation, but this change in gene expression seems to be mediated by changes in methylation status only in the case of pterostilbene.