The prevalence of overweight and obesity is increasing worldwide, causing worry to health and education professionals due to its deleterious effects on cardiovascular health [1], [2]. The presence of cardiometabolic risk factors, such as high blood pressure and alteration of lipid and glycemic profile is already being observed in precocious ages [3]. Several factors can influence this prevalence, including the genetic predisposition to obesity, physical inactivity, low physical fitness levels, and an unhealthy lifestyle [3].

Concerning the genetic predisposition to obesity, there are multifactorial determinants, including monogenic or polygenic factors leading children to develop obesity in adolescence and adult life [4]. Also, obesity can manifest in genetic and physiological indirect ways, providing excessive eating behavior. In this case, the unhealthy behavior can be explained by melanocortin-4 receptor (MC4R) deficiency, which is associated with hyperinsulinemia caused by these eating disorders [5]. Other genetic evidence indicates that FTO gene polymorphism acts in adipose tissue, contributing to increasing obesity, deregulations in eating behavior, and this have a hypothetic negative association with benefic lifestyle and healthy variables, for example fitness and physical activity [4], [6], [7], [8]. Additionally, the genetic mutations in other genes are also associated with obesity and unhealthy habits, including LEP and TMEM18 [8], [9], [10].

The evidence available in the literature indicates that healthy behavior and environmental and social factors seem to minimize the influence of genetic predisposition on body adiposity of the child population [11], [12]. In this context, it is highlighted the role of physical fitness components as important health indicators [13] once higher physical fitness is associated with lower body fat and adequate cardiometabolic risk profile [14]. It has been suggested that cardiorespiratory fitness and strength could attenuate the genetic predisposition to high adiposity in children and adolescents [7], [8]. However, based on recent findings indicating that speed and agility are predictors of changes in cardiometabolic risk factors [14], and that are associated with some specific genotype [15], we hypothesized that these variables could also intervene in the relationship between the genetic predisposition to obesity and adiposity.

Indeed, evidence regarding the associations between obesity and low levels of physical fitness is well documented in different studies and populations, suggesting a genetic and environmental justification for increasing cardiometabolic risk [9], [10], [12], [16]. The present study intends to fill a gap in the literature by investigating the role of specific physical fitness components, agility and speed that seem to exert beneficial effects on cardiometabolic health in youth and could act as moderators in the relationship between the genetic predisposition to obesity and adiposity. Considering this lack of evidence and a possible contribution to minimizing the effect of genetics on cardiometabolic risk by means of promoting exercise interventions in order to increase speed and agility, the present study aimed to verify if there is a moderator role of agility and speed in the relationship between genetic risk score and waist circumference (WC) in adolescents.