Association of the fat mass and obesity-associated (FTO) gene variant (rs9939609) with dietary intake in the Finnish Diabetes Prevention Study.

A cluster of variants in the fat mass and obesity-associated (FTO) gene are associated with the common form of obesity. Well-documented dietary data are required for identifying how the genetic risk can be modified by dietary factors. The objective of the present study was to investigate the associations between the FTO risk allele (rs9939609) and dietary intake, and to evaluate how dietary intake affects the association between FTO and BMI in the Finnish Diabetes Prevention Study during a mean follow-up of 3·2 years. A total of 479 (BMI >25 kg/m2) men and women were genotyped for rs9939609. The participants completed a 3 d food record at baseline and before every annual study visit. The average intakes at baseline and during the years 1, 2 and 3 were calculated. At baseline, the FTO variant rs9939609 was not associated with the mean values of total energy intake, macronutrients or fibre. At baseline, a higher BMI by the FTO risk genotype was detected especially in those who reported a diet high in fat with mean BMI of 30·6 (sd 4·1), 31·3 (sd 4·6) and 34·5 (sd 6·2) kg/m2 for TT, TA and AA carriers, respectively (P =0·005). Higher BMI was also observed in those who had a diet low in carbohydrates (P =0·028) and fibre (P =0·015). However, in the analyses adjusted for total energy intake, age and sex, significant interactions between FTO and dietary intakes were not found. These findings suggest that the association between the FTO genotype and obesity is influenced by the components of dietary intake, and the current dietary recommendations are particularly beneficial for those who are genetically susceptible for obesity.

Gene expression of FTO in human subcutaneous adipose tissue, peripheral blood mononuclear cells and adipocyte cell line.

BACKGROUND/AIMS: The common polymorphism rs9939609 of the fat mass and obesity-associated gene (FTO) is strongly associated with obesity, but the biological function is still unknown. We compared the FTO gene expression in subcutaneous adipose tissue and peripheral blood mononuclear cells (PBMCs) between overweight and normal weight individuals. We also investigated if mRNA levels of FTO in adipose tissue correlated with the adiposity or inflammatory markers and mRNA levels of genes involved in the response to hypoxia (HIF-1a) and cell death(HMGB1). RESULTS: The mRNA expression of FTO in adipose tissue was greater in obese than normal weight individuals (p < 0.001), but there was no difference in FTO expression in PBMCs. FTO mRNA levels did not correlate with adiposity or inflammatory markers and FTO expression was not influenced by the FTO rs9939609 genotype. FTO mRNA level correlated positively with gene expression levels of HIF-1a and HMGB1 in subcutaneous adipose tissue (r = 0.59, p < 0.001; r = 0.69, p < 0.001, respectively; adjusted for BMI and adipocyte cell size). CONCLUSIONS: Altogether, FTO expression appeared not to have a well-defined impact on clinical or biochemical parameters comprising the metabolic syndrome. The correlations with the genes related to hypoxia and cell death suggest novel biological activities for FTO.

The common variant in the FTO gene did not modify the effect of lifestyle changes on body weight: the Finnish Diabetes Prevention Study.

The common single-nucleotide polymorphism in the FTO (fat mass and obesity associated) gene is consistently associated with an increased risk of obesity. However, the knowledge of a potential modifying effect of the FTO gene on changes in body weight achieved by lifestyle intervention is limited. We examined whether the FTO gene variant (rs9939609, T/A) is associated with body weight and BMI and long-term weight changes in the Finnish Diabetes Prevention Study (DPS). Altogether, 522 (aged 40-65 years; BMI >or=25 kg/m(2)) subjects with impaired glucose tolerance (IGT) were randomized to control and lifestyle intervention groups. SNP rs9939609 was genotyped from 502 subjects. At baseline, those with the AA genotype had higher BMI than subjects with other genotypes (P = 0.006). The association was observed in women (P = 0.016) but not in men. During the 4-year follow-up, the subjects with the AA genotype had consistently the highest BMI (P = 0.009) in the entire study population. The magnitude of weight reduction was greater in the intervention group, but the risk allele did not modify weight change in either of the groups. Our results confirm the association between the common FTO variant and BMI in a cross-sectional setting and during the long-term lifestyle intervention. We did not observe association between FTO variant and the magnitude of weight reduction achieved by long-term lifestyle intervention. Based on the results from the DPS, it is unlikely that the common variant of the FTO gene affects the success of lifestyle modification on weight loss.

Effects of fatty and lean fish intake on blood pressure in subjects with coronary heart disease using multiple medications.

BACKGROUND: Intake of fish and long-chain n-3 fatty acids has been of wide interest due to their beneficial effects on cardiovascular risk factors and lower coronary heart disease (CHD) risk. AIM OF THE STUDY: The aim of this pilot study was to examine the effects of fatty fish and lean (white) fish on fatty acid composition of serum lipids and cardiovascular risk factors in subjects with CHD using multiple drugs for this condition. METHODS: The study was an 8-week controlled, parallel intervention. Inclusion criteria were myocardial infarction or unstable ischemic attack, age under 70 years, use of betablockers and presence of sinus rhythm. The subjects were randomized to one of the following groups: 4 meals/week fatty fish (n = 11), 4 meals/week lean fish (n = 12) and control diet including lean meat (n = 10). RESULTS: The mean (+/-SD) of reported fish meals per week was 4.3 +/- 0.4, 4.7 +/- 1.1 and 0.6 +/- 0.4 in the groups, respectively. The proportions of eicosapentaenoic and docosahexaenoic acids in serum lipids increased in the fatty fish group only (P < 0.05). Systolic and diastolic blood pressure levels decreased in the lean fish group (0 vs. 8 week: 3.5 +/- 3.2 and 4.6 +/- 3.6%, respectively, P < 0.05). Serum total triglyceride concentration did not significantly change. HDL cholesterol concentration change differed among groups but without significant post hoc differences. Apolipoprotein A-1 concentration decreased in the control group (0 vs. 8 week, P < 0.05). Coagulation factors, 25-hydroxy vitamin D, and heart rate variability (24 h Holter) did not change among the groups. CONCLUSIONS: Our results suggest that intake of lean fish at least four times per week could reduce blood pressure levels in CHD patients.

Fortified mineral water improves folate status and decreases plasma homocysteine concentration in pregnant women.

OBJECTIVES: There is no mandatory folic acid fortification of food in Finland. We investigated the effects of mineral water fortified with folic acid, vitamins B6, B12, D and calcium on serum and erythrocyte folate concentrations, serum vitamin B12 and plasma homocysteine concentrations in pregnancy. DESIGN: A randomized, controlled, double-blind, parallel-group intervention study. METHODS: Seventy-four pregnant women were recruited from two health care units. The study began at the eleventh week with a two-week run-in period, followed by an eight-week intervention period. The diet was monitored by food records. During the intervention, subjects consumed 1000 mL/day fortified or normal mineral water. The pregnancies were monitored carefully. RESULTS: The folate intake was 255 microg/day in the study group and 274 microg/day in the controls. Serum folate concentrations increased in the study group by 10.3 nmol/L and decreased in the controls by 2.7 nmol/L (P<0.05) during the study. The erythrocyte folate concentrations increased in the study group by 360.9 nmol/L and in the controls by 195.6 nmol/L (P=0.004) and serum homocysteine concentrations fell by 1.1 micromol/L and by 0.3 micromol/L, respectively (P<0.05). CONCLUSIONS: Finnish pregnant women have low dietary folate intake. Fortified mineral water improved folate status and reduced plasma homocysteine concentrations in the pregnant subjects.