Macronutrient Intake-Associated FGF21 Genotype Modifies Effects of Weight-Loss Diets on 2-Year Changes of Central Adiposity and Body Composition: The POUNDS Lost Trial

Abstract

Objective: Fibroblast growth factor 21 (FGF21) is involved in the regulation of energy balance and adipose metabolism. Our previous genome-wide association study identified genetic variants in the FGF21 region associated with macronutrient intake preference. We investigated whether the FGF21 genotype modified effects of weight-loss diets varying in macronutrient intake on changes in adiposity in a 2-year randomized diet intervention trial.

Research design and methods: We genotyped FGF21 rs838147 in 715 overweight or obese individuals who were assigned to one of four diets varying in macronutrient contents. A DEXA scan was performed to evaluate body composition.

Results: We observed a significant interaction between the FGF21 genotype and carbohydrate/fat intake on 2-year changes in waist circumference (WC), percentage of total fat mass, and percentage of trunk fat (P = 0.049, P = 0.001, and P = 0.003 for interaction, respectively). In response to the low-carbohydrate/high-fat diet, carrying the carbohydrate intake-decreasing C allele of rs838147 was marginally associated with less reduction in WC (P = 0.08) and significantly associated with less reduction of total fat mass (P = 0.01) and trunk fat (P = 0.02). Opposite genetic associations with these outcomes were observed among the high-carbohydrate/low-fat diet group; carrying the C allele was associated with a greater reduction of WC, total body fat mass, and trunk fat.

Conclusions: Our data suggest that FGF21 genotypes may interact with dietary carbohydrate/fat intake on changes in central adiposity and body fat composition. A low-calorie, high-carbohydrate/low-fat diet was beneficial for overweight or obese individuals carrying the carbohydrate intake-decreasing allele of the FGF21 variant to improve body composition and abdominal obesity.

Trial registration: ClinicalTrials.gov NCT00072995.

© 2016 by the American Diabetes Association.

Figures

Figure 1

Changes in WC (A), total fat mass percentage (B), and trunk fat percentage (C) according to the FGF21 genetic variant rs838147 and low- or high-carbohydrate diet at 2 years of diet intervention (white bars, FGF21 rs838147 TT genotype; gray bars, TC genotype; black bars, CC genotype). Data are means ± SE values after adjustment for age, sex, ethnicity, and BMI at the baseline examination and value for the respective outcome traits at the baseline examination. CHO, carbohydrate.

Figure 2

Trajectories of WC (A and B), total body fat mass percentage (C and D), and trunk fat percentage (E and F) according to FGF21 variant rs838147 in response to low- or high-carbohydrate diet during the 2-year intervention assessment (black circle and solid line, CC genotype; gray circle and gray solid line, TC genotype; white circle and dotted line, TT genotype). Data are mean ± SE after adjustment for age, sex, ethnicity, BMI at the baseline examination, and value for the respective outcome traits at the baseline examination. P for interaction (genotype × time) after adjustment for age, sex, ethnicity, and BMI at the baseline examination: P > 0.05 (not significant) for A and B; P < 0.001 for C, D, E, and F. P for interaction (genotype × time) after adjustment for age, sex, ethnicity, BMI, and value for the respective outcome traits at the baseline examination: P > 0.05 (not significant) for A and B; P = 0.006 for C; P = 0.01 for D and E; and P = 0.02 for F.