The Impact of FTO Genetic Variants on Obesity and Its Metabolic Consequences is Dependent on Daily Macronutrient Intake

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.

Methylation and Expression of FTO and PLAG1 Genes in Childhood Obesity: Insight into Anthropometric Parameters and Glucose–Lipid Metabolism

“…SNPs have been shown to influence glucose and insulin levels during the oral glucose tolerance test (OGTT) [ 60 ]. However, the impact of methylation and expression of FTO gene region 1 remains undescribed.…”

Association between the FTO SNP rs9939609 and Metabolic Syndrome in Chilean Children

“…Controlling fat intake would modulate the rs9939609 polymorphism and could also help to reduce the effect of this macronutrient on other genetic variants related to metabolic alterations, such as the rs5082 polymorphism of the APOA2 gene and its influence on insulin resistance [62]. In addition, it has recently been found that adapting the intake of different macronutrients to the other genotypes linked to several FTO gene polymorphisms (rs9939609, among them) modifies the risk of obesity and metabolic disorders [63]. This fact means that carriers of the risk allele of the rs9939609 polymorphism, or other FTO gene polymorphisms, could be helped through individualized nutritional interventions [63,64].…”

“…In addition, it has recently been found that adapting the intake of different macronutrients to the other genotypes linked to several FTO gene polymorphisms (rs9939609, among them) modifies the risk of obesity and metabolic disorders [63]. This fact means that carriers of the risk allele of the rs9939609 polymorphism, or other FTO gene polymorphisms, could be helped through individualized nutritional interventions [63,64].…”

Obesity: Epidemiology, Pathophysiology, and Therapeutics

“…3) Polygenic obesity is caused by cumulative contribution of many genes. Further, some people with obesity gain excess weight due to the multiple genes they have ( 53 ), and these genes make them to favor food and thereby have a higher caloric intake. The presence of these types of genes can cause increased caloric intake, increased hunger levels, reduced control overeating, reduced satiety, increased tendency to store body fat, and increased tendency to be sedentary ( 54 ).…”