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BACKGROUND: Few have studied the associations between rs9939609 genotypes in the obesity candidate locus FTO and energy and nutrient intakes and meal frequencies in adults with severe obesity. We are unaware of studies that have assessed adherence to key dietary recommendations in this population, at least in Norway. Increased knowledge of genotype associations with dietary factors could improve personalized obesity therapy. OBJECTIVES: The present study aimed to explore how the rs9939609 genotypes associate with dietary variables and adherence to key dietary recommendations in a sample of adults with severe obesity. METHODS: A cross-sectional observation study designed to have similar numbers of participants with genotypes TT, AT, and AA included 100 patients (70% women) with median (25(th), 75(th) percentile) age 42 (32, 50) y and BMI 42.8 (39.5, 46.4) kg/m(2). We assessed intakes of food groups, energy, and macro- and micronutrients from three 24-h dietary recalls and meal frequencies. Genotype associations were analyzed using regression analyses. Reported intakes were evaluated against national diet recommendations. RESULTS: Using a significance level of 0.01, we found no genotype associations with energy intake, energy density, adherence to recommendations, or meal frequency but tendencies of associations with energy adjusted protein intake (AA > AT, P = 0.037; AT > TT, P = 0.064), food groups milk and cream (AT > TT, P = 0.029), and Mixed dishes (AA > TT, P = 0.039). Few participants complied with recommendations for intakes of whole grains (21%), fruits and vegetables (11%), and fish (37%); however, 67% followed the recommendation to limit added sugar. Less than 20% had recommended intakes of vitamin D and folate. CONCLUSIONS: In our patients with severe obesity, we found tendencies of associations between the FTO rs9939609 genotypes and diet but no significant associations at the 0.01 level and below. Few met key food-based diet recommendations, suggesting that the food habits in this population pose an increased risk of nutrient deficiencies. Curr Dev Nutr 2023;xx:xx.

The objective of the study was to assess associations of the rs9939609 FTO allele to glucose tolerance, hepatic and total insulin sensitivity (IS) in individuals with obesity. From a low-dose hyperinsulinemic euglycemic clamp with glucose-tracer, hepatic IS was assessed by rates of basal and suppressed glucose appearance (Ra), a measure of endogenous glucose production (EGP), and the hepatic insulin resistance index (HIR). Total IS was assessed by rates of glucose infusion (GIR), disappearance (Rd), and metabolic clearance (MCR). From a meal test we assessed IS by the Matsuda index and glucose tolerance by glucose and insulin measurements in the fasted state and postprandially for 2.5 h. The meal test was performed in 97 healthy individuals with BMI ≥35 in similar-sized risk-allele groups (n = 32 T/T, 31 A/T, and 34 A/A), and 79 of them performed the clamp. We analyzed outcomes separately for males and females, and adjusted glucose Ra, Rd, MCR, GIR, and HIR for fat mass. We did not find genotype effects on EGP. Among males, genotype A/A was associated with a significantly lower glucose Rd, MCR, and Matsuda index score relative to genotype T/T. Glucose tolerance was significantly lower in males with genotype A/T vs. T/T and A/A. For females, there were no genotype effects on hepatic or total IS, or on glucose tolerance. Independently of genotypes, females displayed a significantly better hepatic and total IS, and better glucose tolerance than males. We conclude that in subjects with similar obesity we did not register any FTO risk-allele effect on hepatic IS. A FTO risk-allele effect on total IS was registered in males only, findings which need to be reproduced in further studies. Results confirm marked differences in IS between the biological sexes and extend present knowledge by demonstrating a lower endogenous glucose production in females vs. males in uniformly obese individuals. Copyright: © 2021 de Soysa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Purpose The metabolic consequences of carrying a FTO obesity-promoting risk allele have not been fully elucidated and may be confounded by obesity per se. Against this background, we investigated the impact of FTO allele (SNP rs9939609) on fasting and postprandial energy expenditure and fasting substrate expenditure in a study population of uniformly and similarly obese individuals. Procedures We studied a similar number of participants with BMI classes 2–3 (median BMI 42.8 kg/m2) who were either homozygote for the non-risk allele TT (n = 33, numbers increased by enrichment), heterozygote (AT) (n = 32), or homozygote for the risk allele AA (n = 35). Major findings Basal metabolic rate and postprandial energy expenditure did not differ between FTO-groups. However, fasting respiratory quotient (RQ) was increased in those carrying ≥1 risk allele (p = 0.008), whereas postprandial RQ was not. Conclusion In this study population, the FTO-risk allele associates with fasting reduced fat and increased carbohydrate oxidation., Highlights • Fasting RQ associates with FTO risk allele in comparably obese subjects. • The association remained after adjusting for gender effects. • FTO risk not associated with meal-related energy utilization.

Gestational diabetes mellitus (GDM) is associated with maternal diet, however, findings are inconsistent. The aims of the present study were to assess whether intakes of foods and beverages during pregnancy differed between women who developed GDM and non-GDM women, and to compare dietary intakes with dietary recommendations of pregnancy. This is a longitudinal study using participants of a randomized controlled trial. Women with complete measurements of a 75 g oral glucose tolerance test (OGTT) at 18&ndash, 22 and 32&ndash, 36 weeks gestation were included in the cohort (n = 702). Women were diagnosed for GDM according to the simplified International Association of Diabetes and Pregnancy Study Group criteria at 32&ndash, 36 weeks (GDM women: n = 40, non-GDM women: n = 662). Dietary data (food frequency questionnaire) was collected at both time points and compared between GDM and non-GDM women. Variability in OGTT values was assessed in a general linear model. Marginal differences between GDM and non-GDM women in intakes of food groups were found. No associations were found between dietary variables and OGTT values. Not all dietary recommendations were followed in the cohort, with frequently reported alcohol consumption giving largest cause for concern. This study did not find dietary differences that could help explain why 40 women developed GDM.

Background Our aim was to assess the influence of age, gender and lifestyle factors on the effect of the obesity-promoting alleles of FTO and MCR4. Methods The HUNT study comprises health information on the population of Nord-Trøndelag county, Norway. Extreme phenotype participants (gender-wise lower and upper quartiles of waist-hip-ratio and BMI ≥ 35 kg/m2) in the third survey, HUNT3 (2006–08), were genotyped for the single-nucleotide polymorphisms rs9939609 (FTO) and rs17782313 (MC4R); 25686 participants were successfully genotyped. Extreme sampling was chosen to increase power to detect genetic and gene-environment effects on waist-hip-ratio and BMI. Statistical inference was based on linear regression models and a missing-covariate likelihood approach for the extreme phenotype sampling design. Environmental factors were physical activity, diet (artificially sweetened beverages) and smoking. Longitudinal analysis was performed using material from HUNT2 (1995–97). Results Cross-sectional and longitudinal genetic effects indicated stronger genetic associations with obesity in young than in old, as well as differences between women and men. We observed larger genetic effects among physically inactive compared to active individuals. This interaction was age-dependent and seen mainly in 20–40 year olds. We observed a greater FTO effect among men with a regular intake of artificially sweetened beverages, compared to non-drinkers. Interaction analysis of smoking was mainly inconclusive. Conclusions In a large all-adult and area-based population survey the effects of obesity-promoting minor-alleles of FTO and MCR4, and interactions with life style factors are age- and gender-related. These findings appear relevant when designing individualized treatment for and prophylaxis against obesity. © 2017 Bjørnland et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Background Android fat distribution (abdominal obesity) is associated with insulin resistance, hepatic steatosis, and greater secretion of large very low‐density lipoprotein ( VLDL ) particles in men. Since abdominal obesity is becoming increasingly prevalent in women, we aimed to investigate the relationship between android fat and hepatic lipid metabolism in pre‐ and postmenopausal women. Methods and Results We used a combination of stable isotope tracer techniques to investigate intrahepatic fatty acid synthesis and partitioning in 29 lean and 29 abdominally obese women (android fat/total fat 0.065 [0.02 to 0.08] and 0.095 [0.08 to 0.11], respectively). Thirty women were premenopausal aged 35 to 45 and they were matched for abdominal obesity with 28 postmenopausal women aged 55 to 65. As anticipated, abdominal obese women were more insulin resistant with enhanced hepatic secretion of large (404±30 versus 268±26 mg/kg lean mass, P VLDL (160±11 versus 142±13). However, postmenopausal status had a pronounced effect on the characteristics of small VLDL particles, which were considerably triglyceride‐enriched (production ratio of VLDL 2 ‐ triglyceride:apolipoprotein B 30±5.3 versus 19±1.6, P r s =−0.49, P =0.006), de novo lipogenesis ( r s =0.55, P =0.003), and desaturation ( r s =0.48, P =0.012) were closely correlated with abdominal obesity‐driven large VLDL ‐triglyceride secretion rate. Conclusions In women, abdominal obesity is a major driver of hepatic large VLDL particle secretion, whereas postmenopausal status was characterized by increased small VLDL particle size. These data provide a mechanistic basis for the hyperlipidemia observed in postmenopausal obesity.