FTO Genotype and 2-Year Change in Body Composition and Fat Distribution in Response to Weight-Loss Diets

Corresponding author: Lu Qi, .
Diabetes (Impact Factor: 8.1). 08/2012; 61(11):3005-11. DOI: 10.2337/db11-1799
Source: PubMed


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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    • "Follow-up; 742 obese; Adults Interaction with high protein diet nc nc nc (Zhang et al. 2012) rs9939609 Case-cohort; 11 091; Adults No interaction with diet nc nc nc (Vimaleswaran et al. 2012) "
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    ABSTRACT: It is becoming increasingly recognised that early-life nutritional, metabolic and environmental factors can have a long term impact on the early onset of obesity, type 2 diabetes and cardiovascular diseases. Numerous experimental and epidemiological observations support the concept that an individual's response to its adult life-style and nutritional environment depends not only on their genetic susceptibility but also their previous early-life experiences. The current research challenge is to determine the primary pathways contributing to "non- or epi-genetic" causes of excess adult weight gain and adiposity. Evidence from the fields of genetic epidemiology, life-course modelling and diet-induced fetal programming all support a role for the FTO gene in this complex biological interaction. It may provide a missing link in the developmental regulation of energy metabolism. Our review therefore considers the role of the FTO gene in the early-life determination of body weight, body composition and energy balance. We will summarise current knowledge on FTO biology combining human genetic epidemiology, molecular models and findings from animal studies. Notably, we will focus on the role of FTO in energy balance in humans, the importance of FTO polymorphisms in childhood growth and the impact of fetal nutrition. Ultimately we propose a new hypothesis for future research designed to understand the role of FTO in setting gene expression in metabolically active tissues. This article is protected by copyright. All rights reserved.
    Acta Physiologica 11/2013; 210(1). DOI:10.1111/apha.12196 · 4.38 Impact Factor
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    • "In addition to the interaction with BDNF, we observed several nominal interactions with some of the other susceptibility SNPs and diet, and we have earlier in MDCS reported interaction between dietary fat-and carbohydrate levels and the FTO genotype on FM (Sonestedt et al. 2011). Recently, a high-protein diet was found to be beneficial for weight loss and improvement of body composition and fat distribution among risk allele carriers of FTO variant rs1558902 evaluated in a 2-year diet intervention trial (Zhang et al. 2012). Another study conducted a randomized nutritional intervention with a Mediterranean-style-diet . "
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    ABSTRACT: Gene–environment interactions need to be studied to better understand the obesity. We aimed at determining whether genetic susceptibility to obesity associates with diet intake levels and whether diet intakes modify the genetic susceptibility. In 29,480 subjects of the population-based Malmö Diet and Cancer Study (MDCS), we first assessed association between 16 genome-wide association studies identified obesity-related single-nucleotide polymorphisms (SNPs) with body mass index (BMI) and associated traits. We then conducted association analyses between a genetic risk score (GRS) comprising of 13 replicated SNPs and the individual SNPs, and relative dietary intakes of fat, carbohydrates, protein, fiber and total energy intake, as well as interaction analyses on BMI and associated traits among 26,107 nondiabetic MDCS participants. GRS associated strongly with increased BMI (P = 3.6 × 10−34), fat mass (P = 6.3 × 10−28) and fat-free mass (P = 1.3 × 10−24). Higher GRS associated with lower total energy intake (P = 0.001) and higher intake of fiber (P = 2.3 × 10−4). No significant interactions were observed between GRS and the studied dietary intakes on BMI or related traits. Of the individual SNPs, after correcting for multiple comparisons, NEGR1 rs2815752 associated with diet intakes and BDNF rs4923461 showed interaction with protein intake on BMI. In conclusion, our study does not provide evidence for a major role for macronutrient-, fiber- or total energy intake levels in modifying genetic susceptibility to obesity measured as GRS. However, our data suggest that the number of risk alleles as well as some of the individual obesity loci may have a role in regulation of food and energy intake and that some individual loci may interact with diet. Electronic supplementary material The online version of this article (doi:10.1007/s12263-013-0352-8) contains supplementary material, which is available to authorized users.
    Genes & Nutrition 07/2013; 8(6). DOI:10.1007/s12263-013-0352-8 · 2.79 Impact Factor
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    ABSTRACT: Rates of obesity and related complex diseases such as type 2 diabetes and cardiovascular disease have climbed sharply over the past decades, in parallel with shift from principally more active lifestyle and nutritionally dense tradition diet to sedentary lifestyle and more energy-dense, Western-pattern diet. In the past few years, advances in genotyping technology and in particular a number of large-scale genome-wide association studies have made great strides in unraveling the genetic basis of complex diseases; and the growing inventory of genetic variation is facilitating efforts to investigate gene-diet interactions. Understanding gene-diet interaction has the potential to promote diet modifications on the basis of genetic makeup. Several recent large-scale studies found reproducible evidence showing consumption of sugar sweetened beverages or dietary patterns might modulate genetic predisposition to obesity or cardiovascular disease. Analyses in randomized trials also showed that genetic markers for obesity, diabetes, or cardiovascular disease might modify the metabolic response to weight-loss diets. However, little of the knowledge about gene-diet interaction has been applied in public health practice; and opinion on how genetic testing services are offered and interpreted is still divided. This review will summarize recent findings regarding obesogenic diet, genetic susceptibility, and gene-diet interactions for obesity and related complex disorders and will discuss the potential impact of these findings on public health practice.
    12/2012; 1(4):222-227. DOI:10.1007/s13668-012-0029-8
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