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

• Published in: INTERNATIONAL JOURNAL OF OBESITY 2009-11, Vol.33 (11), p.1227-1234
• Main Authors: Grau, K, Hansen, T, Holst, C, Astrup, A, Saris, W H M, Arner, P, Rössner, S, Macdonald, I, Polak, J, Oppert, J-M, Langin, D, Martinez, J A, Pedersen, O, Sørensen, T I A
• Format: Article
• Language: English
• Subjects: Adult; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Biological and medical sciences; Body Mass Index; Body weight; Caloric Restriction; Diet; Diet therapy; Diet, Fat-Restricted; Diet, Reducing; Dietary Carbohydrates - administration & dosage; Dietary fat; Dietary Fats - administration & dosage; Energy; Energy Intake - genetics; Energy Metabolism - genetics; Energy Metabolism - physiology; Environment. Living conditions; Epidemiology; Europe; Female; Genetic aspects; Genetic Predisposition to Disease; Genotype; Health Promotion and Disease Prevention; Hospitals; Humans; Insulin resistance; Internal Medicine; Intervention; Male; Medical sciences; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Miscellaneous; Nutrition research; Obesity; Obesity - diet therapy; Obesity - genetics; original-article; Oxidation; Physiological aspects; Preventive medicine; Proteins - genetics; Public Health; Public health. Hygiene; Public health. Hygiene-occupational medicine; Risk factors; Single nucleotide polymorphisms; Weight control; Young Adult
• ISSN: 0307-0565; 1476-5497; 1476-5497; 0307-0565
• DOI: 10.1038/ijo.2009.159

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.