Dataset Information

Dietary Fat Modifies the Effects of FTO Genotype on Changes in Insulin Sensitivity.

ABSTRACT: BACKGROUND:The common variants in the fat mass and obesity-associated (FTO) gene have been associated with obesity and insulin resistance. Recently, studies also linked FTO variants with macronutrient intakes. OBJECTIVE:We aimed to investigate whether diet interventions varying in macronutrients modified the effects of FTO genotypes on changes in insulin resistance. METHODS:We genotyped FTO variants rs1558902 and rs9939609 and measured insulin resistance in fasting plasma samples at baseline and at 6-mo and 2-y visits in 743 overweight or obese adults (aged 30-70 y, 60% women) from a randomized weight-loss dietary interventional trial, the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial. We assessed interactions between FTO variants and intakes of dietary fat and protein in relation to change in body weight and insulin resistance using generalized estimating equation models. RESULTS:We found significant interactions between rs1558902 and dietary fat on changes in homeostasis model assessment of insulin resistance (HOMA-IR) and insulin (P = 0.003 and 0.004, respectively). Each risk allele (A) of rs1558902 showed a trend to be related to a 0.05-unit less reduction in both log(insulin) and log(HOMA-IR) among the participants assigned to low-fat diets (both P = 0.06), but this was not significantly related to reduction in those assigned to high-fat diets (both P > 0.1) during the 2-y period of intervention. Our data showed that the association between rs9939609 and changes in insulin resistance was not modified by diet macronutrient intakes. CONCLUSIONS:Our results show that carriers of the risk alleles of rs1558902 benefit differently in improving insulin sensitivity by consuming high-fat weight-loss diets rather than low-fat diets. Still, given our data, we acknowledge it is difficult to determine whether fat or carbohydrate contributed to the observed associations.

SUBMITTER: Zheng Y

PROVIDER: S-EPMC4408741 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Dietary Fat Modifies the Effects of FTO Genotype on Changes in Insulin Sensitivity.

Zheng Yan Y Huang Tao T Zhang Xiaomin X Rood Jennifer J Bray George A GA Sacks Frank M FM Qi Lu L

The Journal of nutrition 20150311 5

<h4>Background</h4>The common variants in the fat mass and obesity-associated (FTO) gene have been associated with obesity and insulin resistance. Recently, studies also linked FTO variants with macronutrient intakes.<h4>Objective</h4>We aimed to investigate whether diet interventions varying in macronutrients modified the effects of FTO genotypes on changes in insulin resistance.<h4>Methods</h4>We genotyped FTO variants rs1558902 and rs9939609 and measured insulin resistance in fasting plasma s ...[more]

PMID: 25761503

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Project description:Adiponectin (adipoQ) gene variants have been associated with type 2 diabetes mellitus and insulin resistance. Our aim was to examine whether the presence of several polymorphisms at the adipoQ gene locus (-11391 G > A, -11377 C > G, 45 T > G, and 276 G > T) influences the insulin sensitivity to dietary fat. Healthy volunteers (30 men and 29 women) consumed 3 diets for 4 wk each: an initial period during which all subjects consumed a SFA-rich diet (38% total fat, 20% SFA), followed by a carbohydrate-rich diet (CHO) (30% total fat, 55% carbohydrate) or a monounsaturated fatty acid (MUFA)-rich diet (38% total fat, 22% MUFA) following a randomized, crossover design. After participants consumed each diet, we tested peripheral insulin sensitivity with the insulin suppression test and measured plasma adiponectin concentrations. C/C homozygous men for the -11377 C > G single nucleotide polymorphism (SNP) had a significantly greater decrease in the steady-state plasma glucose concentrations when changing from the SFA-rich (8.95 +/- 0.6 mmol/L) to the MUFA-rich (6.04 +/- 0.31 mmol/L) and CHO-rich (6.35 +/- 0.38 mmol/L) diets than did those carrying the minor G allele (SFA, 6.65 +/- 0.4 mmol/L; MUFA, 6.45 +/- 0.4 mmol/L; CHO, 5.83 +/- 0.3 mmol/L) (P sex x gene x diet interaction = 0.016). These differences did not occur in female participants. Furthermore, C/C men had lower plasma adiponectin concentrations than did C/C women (P sex x gene interaction = 0.015), independently of the dietary fat consumed. None of the variables examined were significantly associated with -11426 A > G, 45T > G, or 276 G > T SNP. In conclusion, C/C homozygous men for the -11377 C > G SNP at adipoQ gene were significantly less insulin resistant after consumption of the MUFA- and CHO-rich diets compared with the SFA-rich diet. This information should help in the identification of vulnerable populations or persons who will benefit from more personalized and mechanism-based dietary recommendations.

Dataset Information

Dietary Fat Modifies the Effects of FTO Genotype on Changes in Insulin Sensitivity.

Publications

Dietary Fat Modifies the Effects of FTO Genotype on Changes in Insulin Sensitivity.

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