Associations between dietary patterns, FTO genotype and obesity in adults from seven European countries.

PURPOSE: High-fat and low-fibre discretionary food intake and FTO genotype are each associated independently with higher risk of obesity. However, few studies have investigated links between obesity and dietary patterns based on discretionary food intake, and the interaction effect of FTO genotype are unknown. Thus, this study aimed to derive dietary patterns based on intake of discretionary foods, saturated fatty acids (SFA) and fibre, and examine cross-sectional associations with BMI and waist circumference (WC), and interaction effects of FTO genotype. METHODS: Baseline data on 1280 adults from seven European countries were included (the Food4Me study). Dietary intake was estimated from a Food Frequency Questionnaire. Reduced rank regression was used to derive three dietary patterns using response variables of discretionary foods, SFA and fibre density. DNA was extracted from buccal swabs. Anthropometrics were self-measured. Linear regression analyses were used to examine associations between dietary patterns and BMI and WC, with an interaction for FTO genotype. RESULTS: Dietary pattern 1 (positively correlated with discretionary foods and SFA, and inversely correlated with fibre) was associated with higher BMI (ß:0.64; 95% CI 0.44, 0.84) and WC (ß:1.58; 95% CI 1.08, 2.07). There was limited evidence dietary pattern 2 (positively correlated with discretionary foods and SFA) and dietary pattern 3 (positively correlated with SFA and fibre) were associated with anthropometrics. FTO risk genotype was associated with higher BMI and WC, with no evidence of a dietary interaction. CONCLUSIONS: Consuming a dietary pattern low in discretionary foods and high-SFA and low-fibre foods is likely to be important for maintaining a healthy weight, regardless of FTO predisposition to obesity. TRIAL REGISTRATION: Clinicaltrials.gov NCT01530139. Registered 9 February 2012 https://clinicaltrials.gov/ct2/show/NCT01530139.

The association of dietary and plasma fatty acid composition with FTO gene expression in human visceral and subcutaneous adipose tissues.

PURPOSE: The human obesity susceptibility gene, FTO, associates with body mass and obesity in humans through regulation of energy expenditure and intake. We aimed to determine how fatty acids in plasma and in diet associate with FTO gene expression in subcutaneous and visceral adipose tissues. METHODS: In this study, 97 participants aged ≥ 18 years were selected from patients admitted to the hospital for abdominal surgeries. Habitual dietary intake of participants was collected using a valid and reliable food frequency questionnaire (FFQ), from which the intake of fatty acids was quantified. Plasma fatty acids were assessed by gas-liquid chromatography. The mRNA expression of the FTO gene in visceral and subcutaneous adipose tissues obtained by biopsy was measured by Real-Time Quantitative Reverse Transcription PCR. Standardized ß-coefficients were calculated by multivariable linear regression. RESULTS: After adjusting for age, homeostasis model insulin resistance index (HOMA-IR), and body mass index, total fatty acid intake was significantly associated with FTO gene expression in visceral (STZß = 0.208, P = 0.037) and subcutaneous (STZß = 0.236, P = 0.020) adipose tissues. Dietary intake of monounsaturated fatty acid (MUFA) and polyunsaturated fatty acids (PUFA) had positive significant associations with the expression of FTO in visceral (STZß = 0.227, P = 0.023; STZß = 0.346, P < 0.001, respectively) and subcutaneous (STZß = 0.227, P = 0.026; STZß = 0.274, P = 0.006, respectively) adipose tissues. There were no associations between plasma fatty acids and FTO mRNA expression in either subcutaneous or visceral adipose tissues. CONCLUSION: The weak association of dietary total fatty acids, MUFA, and PUFA with FTO gene expression in both adipose tissues may highlight the importance of dietary fatty acids composition along with total fat intake in relation to FTO gene expression.

Relation of FTO gene variants to fetal growth trajectories: Findings from the Southampton Women's survey.

INTRODUCTION: Placental function is an important determinant of fetal growth, and fetal growth influences obesity risk in childhood and adult life. Here we investigated how FTO and MC4R gene variants linked with obesity relate to patterns of fetal growth and to placental FTO expression. METHODS: Southampton Women's Survey children (n = 1990) with measurements of fetal growth from 11 to 34 weeks gestation were genotyped for common gene variants in FTO (rs9939609, rs1421085) and MC4R (rs17782313). Linear mixed-effect models were used to analyse relations of gene variants with fetal growth. RESULTS: Fetuses with the rs9939609 A:A FTO genotype had faster biparietal diameter and head circumference growth velocities between 11 and 34 weeks gestation (by 0.012 (95% CI 0.005 to 0.019) and 0.008 (0.002-0.015) standard deviations per week, respectively) compared to fetuses with the T:T FTO genotype; abdominal circumference growth velocity did not differ between genotypes. FTO genotype was not associated with placental FTO expression, but higher placental FTO expression was independently associated with larger fetal size and higher placental ASCT2, EAAT2 and y + LAT2 amino acid transporter expression. Findings were similar for FTO rs1421085, and the MC4R gene variant was associated with the fetal growth velocity of head circumference. DISCUSSION: FTO gene variants are known to associate with obesity but this is the first time that the risk alleles and placental FTO expression have been linked with fetal growth trajectories. The lack of an association between FTO genotype and placental FTO expression adds to emerging evidence of complex biology underlying the association between FTO genotype and obesity.

FTO genotype and weight loss in diet and lifestyle interventions: a systematic review and meta-analysis.

BACKGROUND: Studies have suggested that the fat mass and obesity-associated (FTO) genotype is associated with individual variability in weight loss in response to diet/lifestyle interventions, but results are inconsistent. OBJECTIVE: We aimed to provide a summary of the literature evaluating the relation between the FTO genotype and weight loss in response to diet/lifestyle interventions. DESIGN: A search of English-language articles in the PubMed and Embase databases (through 30 April 2015) was performed. Eligible studies were diet/lifestyle weight-loss intervention studies conducted in adults that reported changes in body weight or body mass index (BMI) by the FTO variant rs9939609 (or its proxy). Differences in weight loss between FTO genotypes across studies were pooled with the use of fixed-effect models. RESULTS: A meta-analysis of 10 studies (comprising 6951 participants) that reported the results of additive genetic models showed that individuals with the FTO TA genotype and AA genotype (those with the obesity-predisposing A allele) had 0.18-kg (95% CI: -0.09-, 0.45-kg;P= 0.19; NS) and 0.44-kg (95% CI: 0.09-, 0.79-kg;P= 0.015) greater weight loss, respectively, than those with the TT genotype. A meta-analysis of 14 studies (comprising 7700 participants) that reported the results of dominant genetic models indicated a 0.20-kg (-0.43-, 0.04-kg) greater weight loss in the TA/AA genotype than in the TT genotype (P= 0.10). In addition, differences in weight loss between the AA genotype and TT genotype were significant in studies with a diet intervention only, adjustment for baseline BMI or body weight, and several other subgroups. However, the relatively small number of studies limited these stratified analyses, and there was no statistically significant difference between subgroups. CONCLUSIONS: This meta-analysis suggests that individuals carrying the homozygous FTO obesity-predisposing allele may lose more weight through diet/lifestyle interventions than noncarriers. Our data provide evidence for genetic variability in response to diet/lifestyle interventions on weight loss, although clinical applications of these findings need further investigations.

FTO gene variation, macronutrient intake and coronary heart disease risk: a gene-diet interaction analysis.

PURPOSE: The fat mass and obesity-associated gene (FTO) is related to obesity and coronary heart disease (CHD). We studied interaction between macronutrient intake and FTO in association with CHD risk or body mass index (BMI). METHODS: The pooled population-based case-control studies, SHEEP and INTERGENE, included 1,381 first-time CHD patients and 4,290 population controls genotyped for FTO rs9939609 (T/A). Diet data were collected in self-administered food frequency questionnaires. Macronutrients were dichotomized into low/high energy percentages (E%) by median levels in controls. Association of FTO genotype (TA/AA vs. TT) with CHD risk was analysed by multiple logistic regression, and with BMI by multiple linear regression. Interaction between FTO and macronutrient was assessed by introducing an interaction term FTO × macronutrient. Interaction on CHD as deviation from additive effects was assessed by calculating relative excess risk due to interaction. RESULTS: No statistically significant interaction was found between FTO genotype and any macronutrient on CHD risk or BMI on either the multiplicative or additive scale. However, FTO genotype (TA/AA vs. TT) was associated with significantly increased CHD risk only in subjects with low E% from fat (OR 1.36, 95% CI 1.11-1.66) or saturated fatty acids (OR 1.36, 95% CI 1.10-1.69), or in subjects with high E% from carbohydrate (OR 1.32, 95% CI 1.07-1.61) or protein (OR 1.41, 95% CI 1.13-1.75). Mean BMI was 0.3-0.6 kg/m(2) higher in control subjects with TA/AA compared to TT, regardless of macronutrient E%. CONCLUSIONS: We found no evidence of interactions between FTO genotype and macronutrient intake on CHD risk or BMI.