☆ 4.7 Article

Association Between FTO Variant and Change in Body Weight and Its Interaction With Dietary Factors: The DiOGenes Study

OBESITY (2012)

期刊

OBESITY

卷 20, 期 8, 页码 1669-1674

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NATURE PUBLISHING GROUP

DOI: 10.1038/oby.2012.49

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Endocrinology & Metabolism Nutrition & Dietetics

资金

DiOGenes project
European Community [FOOD-CT-2005-513946]
Medical Research Council [MC_U106179471] Funding Source: researchfish

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摘要

Although FTO is an established obesity-susceptibility locus, it remains unknown whether it influences weight change in adult life and whether diet attenuates this association. Therefore, we investigated the association of FTO-rs9939609 with changes in weight and waist circumference (WC) during 6.8 years follow-up in a large-scale prospective study and examined whether these associations were modified by dietary energy percentage from fat, protein, carbohydrate, or glycemic index (GI). This study comprised data from five countries of European Prospective Investigation into Cancer and Nutrition (EPIC) and was designed as a case-cohort study for weight gain. Analyses included 11,091 individuals, of whom 5,584 were cases (age (SD), 47.6 (7.5) years), defined as those with the greatest unexplained annual weight gain during follow-up and 5,507 were noncases (48.0 (7.3) years), who were compared in our case-noncase (CNC) analyses. Furthermore, 6,566 individuals (47.9 (7.3) years) selected from the total sample (all noncases and 1,059 cases) formed the random subcohort (RSC), used for continuous trait analyses. Interactions were tested by including interaction terms in the models. In the RSC-analyses, FTO-rs9939609 was associated with BMI (beta (SE), 0.17 (0.08) kg.m(-2)/allele; P = 0.034) and WC (0.47 (0.21) cm/allele; P = 0.026) at baseline, but not with weight change (5.55 (12.5) g.year(-1)/allele; P = 0.66) during follow up. In the CNC-analysis, FTO-rs9939609 was associated with increased risk of being a weight-gainer (OR: 1.1; P = 0.045). We observed no interaction between FTO-rs9939609 and dietary fat, protein and carbohydrate, and GI on BMI and WC at baseline or on change in weight and WC. FTO-rs9939609 is associated with BMI and WC at baseline, but association with weight gain is weak and only observed for extreme gain. Dietary factors did not influence the associations.

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The rs1421085 variant within FTO promotes brown fat thermogenesis

Zhiyin Zhang, Na Chen, Nan Yin, Ruixin Liu, Yang He, Danjie Li, Muye Tong, Aibo Gao, Peng Lu, Yuxiao Zhao, Huabing Li, Junfang Zhang, Dan Zhang, Weiqiong Gu, Jie Hong, Weiqing Wang, Lu Qi, Guang Ning, Jiqiu Wang

Summary: The rs1421085 T>C variant within the FTO gene, which is a genetic risk signal for obesity, is found to be functional in vitro but lacks evidence at the organism level. In this study, researchers recapitulate the homologous human variant in mice and discover that mice carrying the C-allele exhibit increased brown fat thermogenic capacity and resistance to high-fat diet-induced adiposity. Both in vivo and in vitro data suggest that the C-allele enhances the transcription of the Fto gene in brown adipocytes, leading to stronger chromatin looping between the enhancer region and Fto promoter. Furthermore, FTO knockdown or inhibition eliminates the increased thermogenic ability of brown adipocytes carrying the C-allele. These findings establish rs1421085 T>C as a functional variant promoting brown fat thermogenesis.

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