DNA Methylation at ABCG1 and Long-term Changes in Adiposity and Fat Distribution in Response to Dietary Interventions: The POUNDS Lost Trial.

Document Type

Article

Publication Date

12-1-2023

Identifier

DOI: 10.2337/dc23-0748

Abstract

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 whom 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 dietary interventions varying in protein intake (interaction P < 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, whereas 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 (interaction P < 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 benefitted more in long-term reductions in body weight, waist circumference, and body fat distribution when consuming an average-protein diet.

Journal Title

Diabetes care

Volume

46

Issue

12

First Page

2201

Last Page

2207

MeSH Keywords

Humans; Adiposity; DNA Methylation; Dietary Proteins; Diet, Reducing; Obesity; Body Weight; Waist Circumference; Body Mass Index; ATP Binding Cassette Transporter, Subfamily G, Member 1

Keywords

Adiposity; DNA Methylation; Dietary Proteins; Reducing Diet; Obesity; Body Weight; Waist Circumference; Body Mass Index; ATP Binding Cassette Transporter, Subfamily G, Member 1

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