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−1). 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-β) 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=0.002; in AT/AA combined, P=0.003). Among those individuals completing the intervention, we found no effect of FTO rs9939609 genotype on Δweight, ΔFM, ΔFFM, ΔWC or ΔFatOx. However, participants with TT had a smaller reduction in REE on LF than on HF diet (75 kcal/24 h; interaction: P=0.0055). These individuals also showed the greatest reduction in HOMA-β and HOMA-IR (interaction: P=0.0083 and P=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-β and HOMA-IR on LF than on HF diet.
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Acknowledgements
NUGENOB is the acronym of the project ‘Nutrient–Gene interactions in human obesity—implications for dietary guidelines’ supported by the European Community (Contract no. QLK1-CT-2000-00618), see the web-site www.nugenob.org. The study was supported by the European Community (Contract no. QLK1-CT-2000-00618).
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Grau, K., Hansen, T., Holst, C. et al. Macronutrient-specific effect of FTO rs9939609 in response to a 10-week randomized hypo-energetic diet among obese Europeans. Int J Obes 33, 1227–1234 (2009). https://doi.org/10.1038/ijo.2009.159
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DOI: https://doi.org/10.1038/ijo.2009.159
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