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Study Links Epigenetic Markers to Intensive Weight-Loss Program Success

NEW YORK (GenomeWeb News) – A handful of epigenetic biomarkers are associated with good response to an intensive weight-loss program, researchers in Spain reported in The FASEB Journal this week.

The investigators evaluated the DNA methylation levels of obese or overweight Spanish adolescents at the start of a 10-week weight-loss program as well as at the end of the program. From this, they noted that adolescents who were good responders to the program had different baseline DNA methylation levels at certain sites compared to adolescents who did not respond as well to the intervention.

Further, a few of those sites with differential DNA methylation — near AQP9, DUSP22, HIPK3, TNNT1, and TNNI3 — have been linked in previous studies to obesity or weight-loss response.

"Successful obesity treatment during adolescence could reduce morbidity at later stages of life and lead to a better quality of life," Amelia Martí, a professor at the University of Navarra in Pamplona, Spain, said in a statement. "It is crucial to find new markers for obesity treatment."

For this study, Martí and her colleagues drew on the 204 adolescents enrolled in the EVASYON study that is developing and testing weight-loss programs. This program included lifestyle and nutritional education advice from a team of nutritionists, pediatricians, physiotherapists, and psychologists.

Focusing at first on a subset of 24 participants who were the best and worst respondents to the program — judging by weight lost — the investigators examined nearly 27,600 CpG dinucleotides in about 14,500 genes using a methylation array. This implicated seven CpGs in or near seven genes that were differentially methylated between the high- or low-responder groups. Five of those markers were validated by MALDI-TOF mass spectrometry in an additional 83 participants.

"Differences in basal DNA methylation of several CpGs in AQP9, DUSP22, HIPK3, TNNI3, and TNNT1 genes were significantly associated with changes in body weight, BMI-SDS, waist girth, and body fat mass after the weight-loss intervention," the researchers wrote.

Regions near AQP9 and HIPK3, the researchers noted, had been linked previously to weight-loss response or obesity. AQP9 is a facilitative carrier of glycerol, and HIPK3 is involved in a number of cellular processes.

In addition, DUSP22 negatively regulates the IL-6/LIF/STAT3-mediated signaling pathway through the dephosphorylation of STAT3, which is stimulated by leptin. And the TNNT1 gene has been linked to cholesterol levels, though the role of TNNI3 in obesity is not yet known, the researchers said.

The researchers also developed a methylation score based on 97 CpG sites that exhibited differential methylation levels between the high and low responders at the start of the program. The score was associated with weight, BMI-SDS, and body fat mass loss at the end of the intervention, they added.

Such a score could be used to predict weight loss, the researchers said. "Our analysis revealed that the epigenetic pattern based on an epigenetic score calculated from differential baseline methylation of genes between high and low responders to a weight-loss multidisciplinary program could help to predict the individual BMI-SDS decrease in adolescents," they wrote.