DNA Methylation May Explain Differences in Weight Loss

Perhaps one of the most frustrating experiences encountered by patients trying to lose weight, is the variation in weight loss between individuals. Thus, it is not uncommon to see one person easily shedding the pounds, while another, with similar or even greater effort, making little progress.

While, as clinicians it may be tempting to simply blame this on “non-compliance”, a paper by Adriana Moleres and colleagues from the University of Navarra, Pamplona, Spain, published in the FASEB Journal, suggestions that a significant part of this variable response may be attributable to differences in DNA methylation.

As readers may know, methylation of DNA is an important epigenetic phenomenon, whereby certain genes are turned on or off (often forever). These epigenetic changes tend to happen during certain times in human development, including early fetal development and adolescence.

In the current study, Moleres and colleagues compared DNA methylation between adolescent high and low responders to a 10 week multidisciplinary weight loss program.

Using methylation microarrays, the researchers identified five regions located in or near AQP9, DUSP22, HIPK3, TNNT1, and TNNI3 genes that showed significantly differnt methylation levels between high and low responders. Interestingly, the AQP9 and HIPK3 genes have previously been associated with obesity or weight-loss responses.

They were also able to calculate a methylation score that was significantly associated with changes in weight, BMI-SDS, and body fat mass loss after the treatment.

While it is difficult to determine the actual functional effect or mechanisms underlying these epigenetic DNA variations, the findings do point to a “biological” reason that may determine weight loss response to diet and lifestyle interventions.

As I’ve said before, in weight management, one size does not fit all.

AMS
Edmonton, AB

Moleres A, Campión J, Milagro FI, Marcos A, Campoy C, Garagorri JM, Gómez-Martínez S, Martínez JA, Azcona-Sanjulián MC, Martí A, & on behalf of the EVASYON Study Group (2013). Differential DNA methylation patterns between high and low responders to a weight loss intervention in overweight or obese adolescents: the EVASYON study. FASEB journal : official publication of the Federation of American Societies for Experimental Biology PMID: 23475851