DNA methylation at ABCG1 and long-term changes in adiposity and fat distribution in response to diet interventions: the POUNDS Lost trial

Objective: To examine whether participants with different levels of diabetes-related DNA methylation at ABCG1 might respond differently to dietary weight-loss interventions with long-term changes in adiposity and body fat distribution.

Research Design and Methods: The current study included overweight/obese participants from the POUNDS lost trial. Blood levels of regional DNA methylation at ABCG1 were profiled by high-resolution methylC-capture sequencing at baseline among 673 participants, of which 598 were followed up at 6 months and 543 at 2 years. Two-year changes in adiposity and computed tomography measured body fat distribution were calculated.

Results: Regional DNA methylation at ABCG1 showed significantly different associations with long-term changes in body weight and waist circumference at 6 months and 2 years in diet interventions varying in protein intake (P-interaction<0.05 for all). Among participants assigned to an average-protein (15%) diet, lower baseline regional DNA methylation at ABCG1 was associated with greater reductions in body weight and waist circumference at 6 months and 2 years, while opposite associations were found among those assigned to a high-protein (25%) diet. Similar interaction patterns were also observed for body fat distribution, including visceral adipose tissue, subcutaneous adipose tissue, deep subcutaneous adipose tissue, and total adipose tissue at 6 months and 2 years (P-interaction<0.05 for all).

Conclusions: Baseline DNA methylation at ABCG1 interacted with dietary protein intake on long-term decreases in adiposity and body fat distribution. Participants with lower methylation at ABCG1 benefit more in long-term reductions in body weight, waist circumference, and body fat distribution when consuming an average-protein diet.