Abstract 65: DNA Methylation at ABCG1 and Long-Term Changes in Adiposity in Response to Diet Interventions: The POUNDS Lost Trial

Abstract

Introduction: Epigenome-wide association studies identified that DNA methylation (DNAm) at the ABCG1 gene (cg06500161) was associated with obesity. However, little is known about whether DNAm at ABCG1 is associated with long-term changes in adiposity and body fat distribution in response to dietary weight-loss interventions. Hypothesis: We hypothesized that participants with varying DNAm at ABCG1 might respond differently to dietary weight-loss interventions on long-term changes in adiposity and body fat distribution. Methods: The current study included 673 participants with overweight/obesity, who were randomly assigned to 1 of 4 diets varying in macronutrient components. Blood DNAm level was profiled by a high-resolution methylC-capture sequencing at baseline. The regional DNAm at ABCG1 was defined as the average methylation level over CpGs within ± 250 bp of cg06500161. Two-year changes in adiposity and Computed Tomography (CT)-measured body fat distribution were calculated. Results: We found that regional DNAm at ABCG1 significantly interacted with dietary protein intake on long-term changes in body weight and waist circumference (WC) at 6 months and 2 years (P-interaction<0.05 for all, Figure ). Among participants assigned to an average-protein (15%) diet, lower regional DNAm at ABCG1 was associated with greater reductions in body weight and WC at 6 months and 2 years, while opposite associations were found among those assigned to a high-protein (25%) diet. Similar interactions 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). Conclusion: Our data indicate that DNAm at ABCG1 interacted with dietary protein intake on long-term changes in adiposity and body fat distribution. Participants with hypomethylation at ABCG1 benefited more in long-term improvement in adiposity and body fat distribution by consuming an average-protein diet.