L L Blauw1,2, R Noordam3, S Trompet3,4, J F P Berbée1,5, F R Rosendaal2, D van Heemst3, K W van Dijk1,5,6, D O Mook-Kanamori2,7, R de Mutsert2, P C N Rensen1,5. 1. Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands. 2. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands. 3. Department of Medicine, Division of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands. 4. Department Cardiology, Leiden University Medical Center, Leiden, The Netherlands. 5. Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands. 6. Department Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. 7. Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands.
Abstract
BACKGROUND: The fat mass and obesity-associated (FTO) gene harbors the strongest common genetic variant associated with obesity. Recently, rs1421085-T to -C substitution mapped in FTO was shown to induce a developmental shift of human adipocytes from an energy-combusting beige to an energy-storing white phenotype in vitro. As browning of adipocytes selectively enhances fat oxidation (FatOx), we hypothesized that rs1421085-C in FTO is associated with deceased FatOx compared with carbohydrate oxidation (CarbOx) and an increased respiratory quotient (RQ). METHODS: In the Netherlands Epidemiology of Obesity study, a population-based cohort study of middle-aged individuals (45-65 years), anthropometry and genotyping was performed (n=5744), in addition to indirect calorimetry (n=1246). With linear regression analyses, we examined associations of rs1421085 genotype with FatOx, CarbOx and RQ. RESULTS: In the total study population, 36.7% carried the rs1421085-TT genotype, 47.6% rs1421085-CT and 15.7% rs1421085-CC. Mean (s.d.) age was 56 (6) years, mean (s.d.), body mass index (BMI) was 26.3 (4.4) kg m-2 and 56% of the total population were women. Measures of adiposity (difference, 95% confidence interval) were higher in CC carriers compared with that in rs1421085-TT carriers: BMI +0.56 (0.15, 0.98) kg m-2, waist circumference +1.25 (0.02, 2.49) cm and total body fat mass +1.21 (0.28, 2.14) kg. However, no differences in mean FatOx (+2.5 (-2.4, 7.4) mg min-1), CarbOx (-6.1 (-17.4, 5.2) mg min-1) or RQ (-0.01 (-0.02, 0.01)) were observed between the two genotypes. CONCLUSIONS: We observed no evidence for associations of rs1421085 in FTO with FatOx and RQ. This indicates that the rs1421085-C allele in FTO induces obesity likely via other pathways than via reduced FatOx.
BACKGROUND: The fat mass and obesity-associated (FTO) gene harbors the strongest common genetic variant associated with obesity. Recently, rs1421085-T to -C substitution mapped in FTO was shown to induce a developmental shift of human adipocytes from an energy-combusting beige to an energy-storing white phenotype in vitro. As browning of adipocytes selectively enhances fat oxidation (FatOx), we hypothesized that rs1421085-C in FTO is associated with deceased FatOx compared with carbohydrate oxidation (CarbOx) and an increased respiratory quotient (RQ). METHODS: In the Netherlands Epidemiology of Obesity study, a population-based cohort study of middle-aged individuals (45-65 years), anthropometry and genotyping was performed (n=5744), in addition to indirect calorimetry (n=1246). With linear regression analyses, we examined associations of rs1421085 genotype with FatOx, CarbOx and RQ. RESULTS: In the total study population, 36.7% carried the rs1421085-TT genotype, 47.6% rs1421085-CT and 15.7% rs1421085-CC. Mean (s.d.) age was 56 (6) years, mean (s.d.), body mass index (BMI) was 26.3 (4.4) kg m-2 and 56% of the total population were women. Measures of adiposity (difference, 95% confidence interval) were higher in CC carriers compared with that in rs1421085-TT carriers: BMI +0.56 (0.15, 0.98) kg m-2, waist circumference +1.25 (0.02, 2.49) cm and total body fat mass +1.21 (0.28, 2.14) kg. However, no differences in mean FatOx (+2.5 (-2.4, 7.4) mg min-1), CarbOx (-6.1 (-17.4, 5.2) mg min-1) or RQ (-0.01 (-0.02, 0.01)) were observed between the two genotypes. CONCLUSIONS: We observed no evidence for associations of rs1421085 in FTO with FatOx and RQ. This indicates that the rs1421085-C allele in FTO induces obesity likely via other pathways than via reduced FatOx.
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