Macronutrient-specific effect of FTO rs9939609 in response to a 10-week randomized hypo-energetic diet among obese Europeans

Abstract

Background: The A risk allele of rs9939609 of the fat mass-and obesity-associated gene (FTO) increases body fat mass. Objective: To examine whether FTO rs9939609 affects obese individuals' response to a high-fat, low-carbohydrate (CHO) (HF) or low-fat, high-CHO (LF), hypo-energetic diet and whether the effect of the FTO variant depends on dietary fat and CHO content. Design: In a 10-week, European, multi-centre dietary intervention study 771 obese women and men were randomized to either LF (20-25% of energy (%E) from fat, 60-65%E from CHO) or HF (40-45%E from fat, 40-45%E from CHO), hypo-energetic diet (measured resting metabolic rate multiplied by 1.3-600 kcal day À1 ). Body weight, fat mass (FM), fat-free mass (FFM), waist circumference (WC), resting energy expenditure (REE), fasting fat oxidation as % of REE (FatOx), insulin release (HOMA-b) and a surrogate measure of insulin resistance (HOMA-IR) were measured at baseline and after the intervention. In all, 764 individuals were genotyped for FTO rs9939609. Results: For A-allele carriers the drop-out rate was higher on HF than LF diet (in AT, P ¼ 0.002; in AT/AA combined, P ¼ 0.003). Among those individuals completing the intervention, we found no effect of FTO rs9939609 genotype on Dweight, DFM, DFFM, DWC or DFatOx. However, participants with TT had a smaller reduction in REE on LF than on HF diet (75 kcal/24 h; interaction: P ¼ 0.0055). These individuals also showed the greatest reduction in HOMA-b and HOMA-IR (interaction: P ¼ 0.0083 and P ¼ 0.047). Conclusion:The FTO rs9939609 may interact with the macronutrient composition in weight loss diets in various ways; carriers of the A allele on LF diet appear to have a lower risk for drop out, and TT individuals have a smaller decrease in REE and greater decrease in HOMA-b and HOMA-IR on LF than on HF diet.

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

“…In this meta-analysis, each selected study was considered to be a single study unit, and mean weight loss by the FTO genotype groups in the overall study sample, regardless of intervention differences, was taken into account. For studies that reported weight loss for intervention groups separately (15,18,27), we combined the results of different groups with the use of the combining method recommended by the Cochrane Handbook for Systematic Reviews of Interventions (30). We used the same method to combine results of the FTO TA and AA genotype groups for studies that provided results of additive genetic models (16-21, 24, 31).…”

Should animal fats be back on the table? A critical review of the human health effects of animal fat

“…There is a renewed popularity of low carbohydrate high fat diets, as well as the scientific study of them (Foster et al 2003;Volek et al 2003;Yancy et al 2004). Indeed, it now appears that genes contribute to whether one will drop out of a low calorie diet depending on whether it is low fat or high fat (Grau et al 2009). Despite these changes in society, high quality food has always featured animal fats because of their taste and during the past 40 years there has been no deviation from that practice (Escoffier 1921;Bocuse 1988;Carluccio and Contaldo 2012).…”

Macronutrients and type 1 diabetes (revision number 6)

“…Four randomised controlled trials were identified that presented evidence on diets differing in the proportion of carbohydrate to fat or protein in relation to blood glucose response two hours after an oral glucose tolerance test (Swinburn et al, 2001;Lasker et al, 2008;Due et al, 2008a). No further trials were identified in the update search (Cardio-metabolic review, diabetes chapter p185) (Racette et al, 1995;Golay et al, 1996;Golay et al, 2000;Swinburn et al, 2001;Helge, 2002;Colette et al, 2003;Landry et al, 2003;Lovejoy et al, 2003;Wolever & Mehling, 2003;Clifton et al, 2004;Segal-Isaacson et al, 2004;Dansinger et al, 2005;Lofgren et al, 2005;Raatz et al, 2005;Petersen et al, 2006;Howard et al, 2006b;Ebbeling et al, 2007;Gardner et al, 2007;Maki et al, 2007b;Phillips et al, 2008;Due et al, 2008a;Frisch et al, 2009;Grau et al, 2009;Kirk et al, 2009;Morgan et al, 2009;Sacks et al, 2009). Five trials were subsequently identified in the update search (Goree et al, 2011;Haufe et al, 2011;Shikany et al, 2011;Tierney et al, 2011;Brooking et al, 2012 Nearly all trials employ energy restricted weight loss diets that vary both carbohydrate (between 5% and 65% energy) and fat (between 18% and 40% energy) between groups.…”

“…Thirteen randomised controlled trials were identified that presented evidence on diets differing in the proportion of carbohydrate to fat on measures of insulin resistance/sensitivity (Helge, 2002;Wolever & Mehling, 2002;Foster et al, 2003;Lofgren et al, 2005;Raatz et al, 2005;Johnston et al, 2006;Maki et al, 2007b;Tinker et al, 2008;Due et al, 2008a;Grau et al, 2009;Kirk et al, 2009;Sacks et al, 2009;de Luis et al, 2009a). Five trials were subsequently identified in the update search Goree et al, 2011;Haufe et al, 2011;Shikany et al, 2011;Tierney et al, 2011) 5.105.…”

“…Two of these trials report improvements in both diet groups, but this is greater in the lower total carbohydrate intervention (Due et al, 2008a;Kirk et al, 2009). One trial reports that in subjects with the FTO gene TT genotype only, there is a beneficial effect on insulin release in those who consume a higher carbohydrate, lower fat diet (Petersen et al, 2006;Grau et al, 2009). Nearly all trials employ energy restricted weight loss diets that varied both carbohydrate (from 5% to 65% energy) and fat (from 20% to 40% energy) between groups.…”