Physical activity (PA) has been shown to reduce the impact of FTO variation and obesity genetic risk scores (GRS) on BMI. We examined this interaction using a quantitative measure of PA and two adiposity indexes in a longitudinal multi-ethnic study. We analyzed the impact of PA on the association between 14 obesity predisposing variants (analyzed independently and as a GRS) and baseline/follow-up obesity measures in the multi-ethnic prospective cohort EpiDREAM (17423 participants from six ethnic groups). PA was analyzed using basic (low-moderate-high) and quantitative measures (metabolic equivalents (METS)), while BMI and the body adiposity index (BAI) were used to measure obesity. Increased PA was associated with decreased BMI/BAI at baseline/follow-up. FTO rs1421085, CDKAL1 rs2206734, TNNl3K rs1514176, GIPR rs11671664 and the GRS were associated with obesity measures at baseline and/or follow-up. Risk alleles of three SNPs displayed nominal associations with increased (NTRK2 rs1211166, BDNF rs1401635) or decreased (NPC1 rs1805081) basic PA score independently of BMI/BAI. Both basic and quantitative PA measures attenuated the association between FTO rs1421085 risk allele and BMI/BAI at baseline and follow-up. Our results show that physical activity can blunt the genetic effect of FTO rs1421085 on adiposity by 36-75% in a longitudinal multi-ethnic cohort.
Showing posts with label FTO. Show all posts
Showing posts with label FTO. Show all posts
Futurity.org – Obesity gene linked to skin cancer risk
The FTO gene strongly associated with obesity may also increase the risk of malignant melanoma—the most deadly skin cancer.
PLOS Genetics: Emerging Function of Fat Mass and Obesity-Associated Protein (Fto)
Genome-wide association studies (GWAS) are a laborious but powerful tool to identify genetic risk factors associated with complex polygenic traits such as obesity [1], diabetes [2], or coronary artery disease [3]. The link between genetic variation in FTO and obesity was first described in a GWAS for type 2 diabetes [1] and was later independently confirmed in different populations all over the world. First described in 2007, genetic variation in FTO has since become one of the most solidly confirmed risk factor for polygenic obesity in humans; yet, information about how FTO affects metabolism is still scarce. Bioinformatic analyses suggestFTO codes for a Fe(II)- and 2-oxoglutarate–dependent nucleic acid demethylase [4], [5] that catalyzes demethylation of 3-methylthymine in single-stranded DNA [5]. However, how this proposed function of FTO is integrated into the complex network of energy metabolism control remains the object of intense scientific investigation.
FTO Genotype and 2-Year Change in Body Composition and Fat Distribution in Response to Weight-Loss Diets: The POUNDS LOST Trial.
Recent evidence suggests that the fat mass and obesity-associated gene (FTO) genotype may interact with dietary intakes in relation to adiposity. We tested the effect of FTO variant on weight loss in response to 2-year diet interventions. FTO rs1558902 was genotyped in 742 obese adults who were randomly assigned to one of four diets differing in the proportions of fat, protein, and carbohydrate. Body composition and fat distribution were measured by dual-energy x-ray absorptiometry and computed tomography. We found significant modification effects for intervention varying in dietary protein on 2-year changes in fat-free mass, whole body total percentage of fat mass, total adipose tissue mass, visceral adipose tissue mass, and superficial adipose tissue mass (for all interactions, P < 0.05). Carriers of the risk allele had a greater reduction in weight, body composition, and fat distribution in response to a high-protein diet, whereas an opposite genetic effect was observed on changes in fat distribution in response to a low-protein diet. Likewise, significant interaction patterns also were observed at 6 months. Our data suggest that a high-protein diet may be beneficial for weight loss and improvement of body composition and fat distribution in individuals with the risk allele of the FTO variant rs1558902.
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