Hypocaloric diet may partially reverse obesity-related DNA methylation in women

In women with severe obesity, a short-term hypocaloric intervention appears to partially alter the DNA methylation pattern, a recent study has found.

Researchers enrolled 11 women (mean age, 36.9±10.3 years) who were morbidly obese, with an average body mass index of 58.5±10.5 kg/m². Participants were made to undergo 6 weeks of hypocaloric dietary intervention. DNA samples were extracted from peripheral blood leukocytes, and genome-wide DNA methylation analysis was performed before and after the intervention.

Compared against 24 normal-weight controls, women who were obese at baseline had 1,324 CpG sites related to 953 unique genes. Most of the differentially methylated CpG sites (GMCpGs) were hypermethylated in controls relative to obese participants, such that methylation was 11.6-percent higher in controls.

After the dietary intervention, methylation at 16,064 CpG sites were altered, with differences ranging from 10 percent to 35.1 percent. Most DMCpG sites saw an average methylation drop of around 16 percent following the hypocaloric intervention. Notably, genes involved in the Rap1, Ras, and mitogen-activated protein kinase pathways became hypomethylated.

A total of 78,596 DMCpGs were detected when controls were compared with obese participants after the intervention; most (n=62,402) occurred in controls. Hypermethylated sites were related to 8,245 unique genes, several of which were mapped to cancer-related signaling pathways.

“Importantly, the reversion of obesity-related DNA methylation patterns was partial following the intervention. This partial reversion opens a new avenue to explore the clinical implications of the specific modifications in the epigenetic marks reported in this study for the aetiology and management of obesity,” the researchers said.