A dual epigenomic approach for the search of obesity biomarkers: DNA methylation in relation to diet‐induced weight loss

Abstract

Epigenetics could contribute to explain individual differences in weight loss after an energy restriction intervention. Here, we identify novel potential epigenetic biomarkers of weight-loss comparing DNA methylation patterns of high and low responders to a 2 hypocaloric diet. Twenty-five overweight/obese men followed an 8-week caloric restriction intervention. DNA was isolated from peripheral blood mononuclear cells and treated with bisulfite. The basal and endpoint epigenetic differences between high and low responders were analysed by methylation microarray, which was also useful to compare the epigenetic changes due to the nutrition intervention. Subsequently, Sequenom EpiTYPER technology was used to validate several relevant CpGs and the surrounding regions.DNA methylation levels in several CpGs located in ATP10A and CD44 genes showed statistical baseline differences depending on the weight-loss outcome. At the treatment endpoint, DNA methylation levels of several CpGs on WT1 promoter were statistically more methylated in the high than in the low responders. Finally, different CpG sites from WT1 and ATP10A were significantly modified as a result of the intervention.In summary, hypocaloric diet-induced weight loss in humans could alter DNA methylation status of specific genes. Moreover, baseline DNA methylation patterns may be used as epigenetic markers that could help to predict weight loss.

Leptin and TNF-alpha promoter methylation levels measured by MSP could predict the response to a low-calorie diet

“…BSP is a highly accurate but time-consuming technique that implies amplification of the selected region, purification of the PCR products, subcloning into a plasmid and sequencing of the amplified region [16]. In this new approach we sought to apply the MSP technique, more adequate for the diagnosis of a long number of samples, to identify new biomarkers of response to a hypocaloric diet [30].…”

“…However, a previous study of our group [30] analyzed the DNA methylation changes induced by a hypocaloric diet using a methylation microarray assay and a subsequent validation by MALDI-TOF mass spectrometry. This study identified two CpGs in ATP10A and WT1 genes whose methylation profile was modified by the hypocaloric treatment.…”

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

“…In a very interesting article, Feinberg et al (2010) have identified four variably methylated regions (VMRs) that show covariation with body mass index and are located in or near genes implicated in regulating body weight or diabetes. Due to the long time that is needed to perform studies of prognostic biomarkers of obesity in humans, research has been focused on explaining individual differences in weight loss after an energy-restriction intervention (Campion et al, 2009b;Bouchard et al, 2010;Milagro et al, 2011;Cordero et al, 2011a). The most comprehensive studies have performed a DNA methylation array study comparing samples from responders and non-responders to a hypocaloric diet treatment followed by a validation with more individuals and employing a second technique, such as Sequenom EpiTYPER (Bouchard et al, 2010;Milagro et al, 2011).…”

“…In cancer, it is usual to observe sharp changes between both normal and malignant cells, so that epigenetic drugs can be used in relatively high doses to reverse the abnormal methylation patterns and slow down or stop cancer cell growth (Alvarez et al, 2010). In relation to body weight, the reports that have analyzed differences in the percentage of methylation in cytosines of different genes have shown variations of about 10-20% at the most (Bouchard et al, 2010;Milagro et al, 2011). On paper, it seems difficult to modulate the epigenetic drug doses to revert such subtle differences, but the identification in the last years of several nutrients and food compounds that are able to slightly modify the epigenetic patterns of different cell lines and tissues are encouraging in order to look for functional foods that could help to combat or prevent metabolic diseases (vel Szic et al, 2010).…”

Effects of Sirt1 on DNA methylation and expression of genes affected by dietary restriction

“…More recently, effects on DNA methylation in overweight human subjects in response to weight loss diets have begun to emerge. For example, three loci showed increased methylation over a 6-month intervention in subcutaneous adipose tissue in postmenopausal women (Bouchard et al 2010), and methylation at two loci in DNA from peripheral blood mononuclear cells was increased in men following reduced energy intake over 8 weeks (Milagro et al 2011).…”