Abstract
Numerous studies have identified the various fat mass and obesity-associated (FTO) genetic variants associated with obesity and its metabolic consequences; however, the impact of dietary factors on these associations remains unclear. The aim of this study was to evaluate the association between FTO single nucleotide polymorphisms (SNPs), daily macronutrient intake, and obesity and its metabolic consequences. From 1549 Caucasian subjects of Polish origin, genotyped for the FTO SNPs (rs3751812, rs8044769, rs8050136, and rs9939609), 819 subjects were selected for gene–diet interaction analysis. Anthropometric measurements were performed and total body fat content and distribution, blood glucose and insulin concentration during oral glucose tolerance test (OGTT), and lipid profile were determined. Macronutrient intake was analyzed based on three-day food records, and daily physical activity levels were evaluated using the International Physical Activity Questionnaire Long Form (IPAQ-LF). Our study shows that carriers of the GG genotype of rs3751812 presented lower body weight, body mass index (BMI), total body fat content, and hip and waist circumference and presented lower obesity-related markers if more than 48% of daily energy intake was derived from carbohydrates and lower subcutaneous and visceral fat content when energy intake derived from dietary fat did not exceed 30%. Similar results were observed for rs8050136 CC genotype carriers. We did not notice any significant differences in obesity markers between genotypes of rs8044769, but we did observe a significant impact of diet-gene associations. Body weight and BMI were significantly higher in TT and CT genotype carriers if daily energy intake derived from carbohydrates was less than 48%. Moreover, in TT genotype carriers, we observed higher blood glucose concentration while fasting and during the OGTT test if more than 18% of total energy intake was derived from proteins. In conclusion, our results indicate that daily macronutrient intake may modulate the impact of FTO genetic SNPs on obesity and obesity-related metabolic consequences.
Highlights
Obesity is a major public health problem worldwide [1] and a leading risk factor for type 2 diabetes mellitus in adolescents [2,3] and children [3,4]
Obesity is a result of imbalanced energy homeostasis, but genome-wide association studies have identified many single nucleotide polymorphisms (SNPs) in the fat mass and obesity-associated (FTO) gene, melanocortin-4 receptor (MC4R) gene, and other genes [8,9] that are associated with the risk of developing obesity
Among the investigated FTO SNPs, some of the loci were in very strong linkage disequilibrium (D’ = 1.0 for rs8050136 and rs9939609) [25], so we present results for rs8050136
Summary
Obesity is a major public health problem worldwide [1] and a leading risk factor for type 2 diabetes mellitus in adolescents [2,3] and children [3,4]. Obesity is a result of imbalanced energy homeostasis, but genome-wide association studies have identified many single nucleotide polymorphisms (SNPs) in the fat mass and obesity-associated (FTO) gene, melanocortin-4 receptor (MC4R) gene, and other genes [8,9] that are associated with the risk of developing obesity Among these genes, FTO has been reported as the gene with the strongest significant correlation with obesity [10]. FTO rs9939609 SNPs have been associated with increased macronutrient consumption, especially fat and carbohydrates, as well as total energy intake [11,14,15], but these genetic variants do not seem to influence energy expenditure [11,16] Environmental factors such as diet may influence the associations between genetic risk and obesity development. The aim of our study was to evaluate whether daily macronutrient intake could modify the association between genetic variations of the FTO gene and obesity and obesity-related metabolic consequences among the Polish population
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