FTO genotype and 2-year change in body composition and fat distribution in response to weight-loss diets: the POUNDS LOST Trial

Xiaomin Zhang, Qibin Qi, Cuilin Zhang, Steven R Smith, Frank B Hu, Frank M Sacks, George A Bray, Lu Qi, Xiaomin Zhang, Qibin Qi, Cuilin Zhang, Steven R Smith, Frank B Hu, Frank M Sacks, George A Bray, Lu Qi

Abstract

Recent evidence suggests that the fat mass and obesity-associated gene (FTO) genotype may interact with dietary intakes in relation to adiposity. We tested the effect of FTO variant on weight loss in response to 2-year diet interventions. FTO rs1558902 was genotyped in 742 obese adults who were randomly assigned to one of four diets differing in the proportions of fat, protein, and carbohydrate. Body composition and fat distribution were measured by dual-energy x-ray absorptiometry and computed tomography. We found significant modification effects for intervention varying in dietary protein on 2-year changes in fat-free mass, whole body total percentage of fat mass, total adipose tissue mass, visceral adipose tissue mass, and superficial adipose tissue mass (for all interactions, P < 0.05). Carriers of the risk allele had a greater reduction in weight, body composition, and fat distribution in response to a high-protein diet, whereas an opposite genetic effect was observed on changes in fat distribution in response to a low-protein diet. Likewise, significant interaction patterns also were observed at 6 months. Our data suggest that a high-protein diet may be beneficial for weight loss and improvement of body composition and fat distribution in individuals with the risk allele of the FTO variant rs1558902.

Figures

FIG. 1.
FIG. 1.
Interaction between the FTO rs1558902 genotype and dietary protein intervention on changes in total fat (A), FFM (B), FM% (C), and percentage of trunk fat (D) at 6 months and 2 years. P values are adjusted for age, sex, ethnicity, carbohydrate, baseline values for respective outcomes, and baseline BMI. Data included 52 and 60 (TT), 66 and 73 (TA), and 31 and 28 (AA) participants in the low-protein group and the high-protein group at 6 months, respectively (total n = 310), and 34 and 44 (TT), 46 and 61 (TA), and 19 and 20 (AA) participants in the low-protein group and the high-protein group at 2 years, respectively (total n = 224).
FIG. 2.
FIG. 2.
Interaction between the FTO rs1558902 genotype and dietary protein intervention on changes in TAT (A), VAT (B), DSAT (C), and SAT (D) at 6 months and 2 years. P values are adjusted for age, sex, ethnicity, carbohydrate, baseline values for respective outcomes, and baseline BMI. Data included 17, 18, 18, and 17 (TT); 30, 35, 35, and 30 (TA); and 10, 13, 13, and 10 (AA) participants in the low-protein group and 18, 22, 22, and 18 (TT); 26, 35, 35, and 26 (TA); and 12, 14, 14, and 12 (AA) in the high-protein group for TAT, VAT, DSAT, and SAT at 6 months (total n = 137); and 12, 15, 15, and 12 (TT); 18, 25, 25, and 18 (TA); and 8, 9, 9, and 8 (AA) participants in the low-protein group and 15, 17, 17, and 15 (TT); 23, 30, 30, and 23 (TA); and 8, 9, 9, and 8 (AA) in the high-protein group for TAT, VAT, DSAT, and SAT at 2 years (total n = 105).
FIG. 3.
FIG. 3.
Changes in total fat (A), FFM (B), FM% (C), and percentage of trunk fat (D) in the low-protein and the high-protein diet groups according to the FTO rs1558902 genotype from baseline to 6 months and 2 years. P values are adjusted for age, sex, ethnicity, carbohydrate, baseline values for respective outcomes, and baseline BMI. Data included 198, 149, and 99 in the low-protein group and 193, 161, and 125 in the high-protein group for body composition at baseline, 6 months and 2 years, respectively. (A high-quality color representation of this figure is available in the online issue.)
FIG. 4.
FIG. 4.
Changes in TAT (A), VAT (B), DSAT (C), and SAT (D) in the low-protein and high-protein diet groups according to the FTO rs1558902 genotype from baseline to 6 months and 2 years. P values are adjusted for age, sex, ethnicity, carbohydrate, baseline values for respective outcomes, and baseline BMI. Data included values at baseline and at 6 months and 2 years for 80, 57, and 38 participants, respectively, for TAT and SAT and 89, 66, and 49 participants, respectively, for VAT and DSAT in the low-protein group; and 71, 56, and 46 participants, respectively, for TAT and SAT and 86, 71, and 56 participants, respectively, for VAT and DSAT in the high-protein group. (A high-quality color representation of this figure is available in the online issue.)

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