Aging, Environment, & DiseaseDNA Methylation and Hydroxymethylation

Want To Lose More Weight With Less Effort? Epigenetics Can Help.

lose_weightGenetic and lifestyle factors both play important roles in controlling our weight, and epigenetics has recently emerged as a powerful new tool to study the effects of lifestyle on obesity. Epigenetic mechanisms regulate heritable patterns of gene expression without changes in the DNA sequence through numerous processes, including DNA methylation and histone modification. Adolescence is considered a significant window in life during which obesity increases the risk for many adult diseases, including cardiovascular disease and even cancer. However, little is known about the relationship between DNA methylation patterns and outcomes of weight loss interventions. A recent paper provides such information by genome-wide methylation profiling of obese adolescents in the Spanish EVASYON study.

Moleres et al. looked into possible epigenetic differences between high and low responders to a 10-week multidisciplinary weight loss program in 204 overweight or obese adolescents. The weight loss program included a personalized balanced diet, a physical activity program, and a weekly meeting where participants received nutritional and physical advice and psychological support. Data such as weight, body mass index-standard deviation score (BMI-SDS), and body fat mass were collected at both the start and end of the treatment. Those losing > 1.1 in their BMI-SDS scores were considered high responders while those that lost < 0.4 were considered low responders. DNA methylation patterns in blood samples were determined prior to the start of the program using the Illumina 27k methylation array. The assay identified 97 differentially methylated CpG sites between high and low responders (12 subjects/group). The involved genes belong to networks related to cancer, inflammatory response, cell cycle, immune cell trafficking, hematological system development and function. Validation of relevant DNA methylation biomarkers was performed in 107 subjects using base-specific cleavage followed by MALDI-TOF mass spectrometry. Seven CpG sites from or near seven genes were selected for validation and significant methylation changes at five of these genes were confirmed.

Interestingly, a strong positive correlation was observed between a baseline epigenetic score and BMI-SDS change. The epigenetic score for each adolescent was cumulative, based on the 97 CpG sites, and the higher the DNA methylation level, the higher the score. In addition, differences in basal DNA methylation of several CpG sites in the AQP9, DUSP22, HIPK3, TNNI3, and TNNT1 genes were significantly associated with changes in body measurements after the weight loss treatment. AQP9 and HIPK3 have been previously reported in obesity and weight loss response. Overexpression of AQP9 may cause increased lipogenesis and HIPK3 was found hypermethylated in lean compared with obese subjects. Elevated DUSP22 expression could inhibit obesity-derived chronic inflammation regulating gluconeogenesis. Increased expression of TNNT1 has been positively associated with total cholesterol. TNNI3’s implication in obesity is not clear.

This study demonstrated that a person’s epigenetic profile can predict the outcome of a weight loss treatment and may assist in developing new obesity therapies. It is even more important for adolescents because adolescent obesity has been an independent risk factor for many adult diseases. In the future, personalized diet and weight loss treatment aided by utilizing individual epigenetic profiles may prove more effective, economical and require less effort than many current diets. With a genetic and epigenetic knowledge-backed weight loss program, people may be able to achieve their optimal body weight and easily keep it that way. What do you think about this new paradigm of weight loss intervention? Are you open to taking an epigenetic evaluation before starting your weight loss program?


Moleres A, Campión J, Milagro FI, Marcos A, Campoy C, Garagorri JM, Gómez-Martínez S, Martínez JA, Azcona-Sanjulián MC, & Martí A (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, 27 (6), 2504-12 PMID: 23475851

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Wei G.

Wei G.

Wei earned a Ph.D. in Microbiology from University of Iowa and received his postdoctoral training in Bioinformatics. For the last ten years, he has developed and provided bioinformatics applications and services in the genomics and diagnostics industry. Wei enjoys reading, jogging, and playing with his two lovely kids.