Abstract
PurposeThe interactions between lifestyle and genetic factors play an important role in obesity development. Mutations in melanocortin-4-receptor (MC4R) gene are one of the most common cause of monogenic obesity, however, the functional effects of polymorphic variants near MC4R gene in general populations remain uncertain. The aim of our study was to analyze whether the common single nucleotide polymorphisms (SNPs) of MC4R gene influence the food preferences, physical activity, body fat content and distribution, as well as fasting and postprandial energy expenditure and substrates utilization.MethodsWe genotyped previously identified MC4R SNPs: rs17782313, rs633265, rs1350341, rs12970134 in 927 subjects, who underwent anthropometric, total body fat content, visceral (VAT) and subcutaneous adipose tissue (SAT) measurements, and daily physical activity and dietary intake analysis. In randomly selected 47 subjects the energy expenditure, carbohydrate and lipid utilizations were evaluated in fasting state and after high-carbohydrate and control meals intake.ResultsWe found the significant associations between studied SNPs of MC4R gene and VAT and VAT/SAT ratio. Moreover, the GG genotype carriers of rs1350341, who had the lowest VAT accumulation (p = 0.012), presented higher relative increase in postprandial carbohydrate utilization (p = 0.013, p = 0.024).ConclusionsWe have observed that common SNPs of the MC4R gene influence the body fat content and distribution, as well as relative increase in postprandial carbohydrate utilization. We believe that our study may help to understand better the impact of MC4R gene on obesity development, and to help to provide personalized prevention/treatment strategies to fight against obesity and its metabolic consequences.
Highlights
The prevalence of obesity is rapidly increasing worldwide, and it has become an important clinical problem [1]
The large-scale genome-wide association studies (GWAS) and meta-analyzes have revealed over 52 new loci, including single nucleotide polymorphisms (SNPs) in or near the fat mass and obesity-associated (FTO) gene, melanocortin-4 receptor (MC4R) gene, Peroxisome proliferator-activated receptor gamma (PPAR), brain-derived neurotrophic factor (BDNF), 1 3 Vol.:(0123456789)
We have not noticed any associations between rs17782313 and energy intake, dietary intake, physical activity, energy expenditure, nor substrate utilizations during meal challenge tests
Summary
The prevalence of obesity is rapidly increasing worldwide, and it has become an important clinical problem [1] This multifactorial disorder is a major risk factor of type 2 diabetes mellitus (T2DM), hypertension, hyperlipidemia, cardiovascular diseases and the increase in the obesity development can lead to further morbidity and mortality [2, 3]. The increasing prevalence of obesity and T2DM in the modern environment generally can be contributed by the excessive energy intake, and/or by changes in dietary habits dependent on the age, as well as by diminished physical activity, and it is already known, that these diseases may be influenced by interaction between lifestyle and genetic factors [6, 15, 16], which can modulate the impact of the environment on each individual’s risk
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