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

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posted on 2023-09-29, 00:00 authored by Xiang LiXiang Li, Xiaojian SHAOXiaojian SHAO, Minghao Kou, Xuan WangXuan Wang, Hao MaHao Ma, Elin Grundberg, Lydia A Bazzano, Steven R. Smith, George A Bray, Frank M Sacks, Lu QiLu Qi

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.


The study was supported by grants from the National Heart, Lung, and Blood Institute (HL071981, HL034594, HL126024), the National Institute of Diabetes and Digestive and Kidney Diseases (DK115679, DK091718, DK100383), the Fogarty International Center (TW010790), and Tulane Research Centers of Excellence Awards. Xiang Li was the recipient of the American Heart Association Predoctoral Fellowship Award (19PRE34380036).