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Research Project: Chemistry of Natural Products for Nutraceutical Use, Pest Management and Crop Development

Location: Natural Products Utilization Research

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

item Gracia, Ana
item Elcoroaristizabal, Xabier
item Fernandez-quintela, Alfredo
item Miranda, Jonathan
item Bediaga, Naiara
item De Pancorbo, Marian
item Rimando, Agnes
item Portillo, Maria

Submitted to: Genes and Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/20/2014
Publication Date: 6/6/2014
Publication URL:
Citation: Gracia, A., Elcoroaristizabal, X., Fernandez-Quintela, A., Miranda, J., Bediaga, N.G., De Pancorbo, M.M., Rimando, A.M., Portillo, M.P. 2014. Fatty acid synthase methylation levels in adipose tissue: effects of an obesogenic diet and phenolic compounds. Genes and Nutrition. 9:411. DOI 10.1007/s12263-014-0411-9.

Interpretive Summary: Epigenetic processes are events that regulate heritable changes in gene activity. Addition of methyl group to genes is one such event, which can inhibit proper processing of gene information. DNA methylation has been reported to play a critical role in the development of Type-2 diabetes. A few studies also have shown association between DNA methylation and measures of obesity. We conducted a study to assess changes in the methylation pattern of genes induced by high-fat, high-sucrose (HFHS) diet, and to determine whether the pattern can be altered by the phenolic compounds resveratrol and pterostilbene. The HFHS diet induced a significant increase in adipose tissue weight. Both compounds partially prevented this effect. In one of the genes involve in fatty acid synthesis, the fatty acid synthase gene, the HFHS diet induced a significant lower methylation in position -90pb and significant hypermethylation in -62bp position. Pterostilbene reversed the changes in methylation pattern induced by the diet, but not resveratrol. Both polyphenols averted the up-regulation of the fatty acid synthase gene, but under our experimental conditions reversal of changes in methylation status induced by HFHS diet was observed only with pterostilbene. Our results suggest pterostilbene is a promising compound to reverse undesirable DNA methylation changes caused by HFHS diet, and could arrest development of different diseases.

Technical Abstract: 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 (HFS), the resveratrol-treated group (RSV; 30 mg/kg/d) and the pterostilbene-treated group (PT; 30 mg/kg/d). 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 -90bp position and significant hypermethylation in -62bp 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 polyphenols averted fasn up-regulation. These results demonstrate that the up-regulation of fasn gene induced by an obesogenic feeding, based in a high-fat high-sucrose diet, is related to hypomethylation of this gene in position -90bp. Under our experimental conditions, both polyphenols 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.