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Diabetes Care. 2016 Nov;39(11):1909-1914. Epub 2016 Aug 31.

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.

Author information

1
Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA.
2
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
3
Epidemiology Domain, Saw Swee Hock School of Public Health and Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
4
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
5
Florida Hospital and Sanford-Burnham Institute, Orlando, FL.
6
Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA.
7
Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA lqi1@tulane.edu.
8
Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

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.

PMID:
27581055
PMCID:
PMC5079612
DOI:
10.2337/dc16-1111
[Indexed for MEDLINE]
Free PMC Article

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