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Macronutrient intake as a mediator with FTO to increase body mass index.

TitleMacronutrient intake as a mediator with FTO to increase body mass index.
Publication TypeJournal Article
Year of Publication2014
AuthorsHardy DS, Racette SB
Secondary AuthorsHoelscher DM
JournalJ Am Coll Nutr
Date Published2014
KeywordsAfrican Americans, Aged, Alleles, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Body Mass Index, Cross-Sectional Studies, Dietary Carbohydrates, Dietary Fats, Dietary Proteins, Energy Intake, European Continental Ancestry Group, Female, Homozygote, Humans, Linear Models, Male, Middle Aged, Polymorphism, Single Nucleotide, Proteins, Surveys and Questionnaires

BACKGROUND: The fat mass and obesity-associated (FTO) single nucleotide polymorphisms (SNPs; rs1421085, rs17817449, rs9939609, rs8050136) and macronutrient intake (carbohydrate, protein, fat, total calories) are associated with body mass index (BMI). However, the mechanism for this relationship has not been fully elucidated.

OBJECTIVE: This study examined whether macronutrient intake mediates the association between FTO SNPs and BMI.

DESIGN: Baseline cross-sectional data from the Atherosclerosis Risk in Communities (ARIC) study of whites (n = 10,176) and African Americans (n = 3641) aged 45 to 64 years were analyzed.

RESULTS: In linear regression models with BMI as the dependent variable, FTO SNPs were significantly associated with higher BMI after adjusting for covariates. The addition of energy-adjusted macronutrients attenuated the FTO effect estimates, indicating partial mediation. In whites, β ranged from 0.40 (95% confidence interval [CI], 0.20, 0.60) for rs17817449 heterozygous carriers to 0.93 (95% CI, 0.64, 122) for rs8050136 homozygous carriers; for African Americans rs17817449 homozygous carriers β was 0.65 (95% CI, 0.03, 1.27). In models with macronutrient intake as the dependent variable, all FTO SNPs were associated with higher protein intake for homozygous carriers after adjusting for BMI and other covariates. Among whites, β ranged from 1.44 (95% CI, 0.51, 2.37) for rs8050136 to 1.73 (95% CI, 0.85, 2.61) for rs17817449; among African American rs8050136 homozygous carriers β was 2.46 (95% CI, 0.77, 4.14). In mediation analysis, in whites only, FTO high-risk alleles were associated with higher BMI partly through their small effects on carbohydrate and protein intake.

CONCLUSIONS: These findings suggest that in adults, the relationship between FTO variants and BMI is not primarily through mediation of food intake.

Alternate JournalJ Am Coll Nutr
PubMed ID25144299