Introduction
The global prevalence of adolescent overweight and obesity has been increasing dramatically in recent decades [
1], reaching rates of 5.6% (previously 0.7%) and 7.8% (previously 0.9%) for girls and boys aged 5–19 years old, respectively [
2]. According to the World Obesity Federation in 2019, about 206 million children and adolescents of the age group of 5–19 years will be affected by obesity by 2025, and this number is expected to increase to 254 million by 2030 [
3]. Studies have shown the association of adolescent obesity with several common adulthood diseases, such as diabetes, malignancies, and cardiovascular diseases [
4]. Adolescent overweight is defined as having a Body Mass Index (BMI) higher than one Standard Deviation (SD) over the median of the growth reference curve for a given age by the World Health Organization (WHO), while adolescent obesity is defined as having a BMI higher than two SD over the related median [
5]. Nowadays, it is agreed upon that obesity is a multifactorial disease affected by genetic factors and environment, such as lifestyle [
6]. It has been reported that lack of physical activity and high-calorie foods are the main causes of obesity in adolescents. However, genetic and hormonal factors may also play a role [
7].
According to a recent study, obesity has a genetic origin, which can be multi- or monogenic. Moreover, it has been shown that multigenic obesity is quite common, while monogenic causes of obesity are rare [
8]. For example, the Fat mass and obesity-associated (FTO) gene plays a crucial role in obesity [
9], and adolescent overweight and obesity are strongly associated with Single Nucleotide Polymorphisms (SNPs) of the FTO gene [
10]. According to the Genome-Wide Association Studies (GWAS), SNPs of the FTO gene have an essential role in regulating fat mass and adipogenesis [
11]. These obesity-associated SNPs may increase body weight by altering the expression of other genes, such as IRX3 and RPGRIP1L, rather than the FTO gene [
12]. Also, the SNPs of the FTO gene can regulate energy intake since the carriers of the high-risk allele of FTO consume more high-calorie food, especially fats and sugars [
13], and have poor eating habits and decreased satiety levels [
13]. A study on overweight children showed that the rs9939609 allele of the FTO gene was associated with greater food responses, food satisfaction, emotional eating, lower satiety responses, and eating slowness [
14].
Thus, the FTO genotype may influence eating behavior by regulating energy intake instead of energy expenditure [
15]. Several studies have reported a relationship between the SNPs of FTO and intake of energy and macronutrients. However, others have reported incompatible results. For example, a study reported that adults with the high-risk allele consumed fewer calories and more protein [
16]. Moreover, a study by Huang et al. (2014) reported that hypocaloric weight loss diets reduced the food desires and appetite of individuals carrying the obesity-prone allele of the FTO [
17]. However, the exact underlying mechanism of the effect of FTO genotype on obesity is not illustrated yet. Also, few studies have examined the effects of the SNPs of the FTO gene on the appetites of adolescents. On the other hand, the prevalence of adolescent obesity has also increased in Iran. For example, it has increased from 3.9% to 2000 to 9.3% in 2016 in 10-19-year-old boys [
18]. Therefore, the present study aimed to investigate the relationship between the FTO genotype and resistance to eating in Iranian male adolescents.
Discussion
The present study reported a significant reverse relationship between the FTO rs9930506 genotype and resistance to eating that remained significant after adjusting for different confounding factors. Moreover, the participants with low resistance to eating were significantly older and had significantly lower nutritional knowledge compared to those with high resistance to eating. Previous studies have shown that teenagers show more unhealthy eating behavior as they get older [
27,
28]. This can be explained by the fact that older teenagers are more likely to be exposed to advertisements of unhealthy food on social networks, which decreases their self-regulation of food intake [
29]. Also, studies have shown that increased nutritional knowledge helps individuals of all age groups, including teenagers, adopt healthier eating habits [
30,
31].
On the other hand, the present study did not show a significant relationship between resistance to eating and consumption of certain food categories, such as grains, nuts, meats, dairy, vegetables, fruits, oils, and junk food. According to previous studies, a diet high in vegetables is associated with high satiety and less desire for sweet, salty, and fatty foods [
32]. Moreover, a review showed that nuts can suppress hunger and desire to eat, leading to a feeling of fullness [
33]. These findings are not compatible with ours, which can be explained by differences in data collection methods. The mentioned studies used a self-reported FFQ questionnaire for food intake assessment, which allows for potential reporting errors.
Recent studies have shown a relationship between FTO and obesity-related indices in early adolescents [
34]. However, the exact mechanism of the effect of the FTO gene on body weight is not illustrated yet. According to several studies, the rs9939609 polymorphism of the FTO gene may be involved in regulating satiety and eating behaviors in children and adolescents [
35,
36]. A study by Rivas et al. (2018) reported that the children with the risk allele of FTO had lower scores in satiety measures while higher scores in food responsiveness and emotional eating measures compared to other children [
14], which was compatible with our findings. Moreover, a study by Ranzenhofer et al. (2019) showed a significant relationship between FTO and food intake in non-obese 5-10-year-old children whose adiposity was lower or equal to the 95th percentile [
37]. Also, the studies by Emond et al. (2017) and Wardle et al. (2008) reported that children and adolescents who were carriers of the FTO risk alleles had less feeling of satiety and higher energy intake compared to others [
13,
35].
Another study by Wardle et al. (2009) reported higher energy intake in children with the FTO risk alleles, which may lead to eating in the absence of hunger. Thus, carriers of the risk alleles of FTO may have low levels of eating control [
36]. Moreover, several studies have investigated the effect of the rs9939609 polymorphism of the FTO gene on satiety and eating patterns in adults, reporting that the adults with the risk allele had lower levels of satiety and control on eating [
38]. For example, a recent study by Melhorn et al. (2018) reported that the individuals with the risk allele had less feelings of fullness, consumed more calories, and attributed greater appeal to high-fat foods compared to other participants [
38]. All these studies are compatible with our findings, suggesting that those carrying the risk allele may not manifest resistance to eating.
Several mechanisms have been suggested for the effect of the FTO gene on resistance to eating, including its effect on satiety through the Central Nervous System (CNS) and the levels of ghrelin and leptin [
38,
39]. It is believed that the risk allele of the FTO gene disrupts leptin signaling through CNS, thereby increasing the size of the meals [
40,
41]. This process is probably through attenuating the satiety-enhancing effect of leptin in the hindbrain or modulating mesolimbic dopamine signals [
42]. Moreover, it has been shown that the rs9939609 polymorphism of the FTO gene can alter the responsiveness of CNS to cerebral ghrelin levels, possibly through mRNA expression and methylation. Such a process is a potential mediating pathway between the risk alleles of the FTO gene and obesity [
17,
43].
Individuals with the rs9939609 polymorphism of the FTO are markedly different from others in neural responsiveness to food cues in cerebral regions responsible for energy homeostasis control, reward, and incentive motivation [
44]. Allelic variations in the FTO gene may lead to persistent postprandial cerebral activation by visual cues of calorie-dense foods in the extended satiety network previously shown to mediate appetite, which in turn leads to increased ad libitum caloric intake [
45]. Thus, those with the risk allele of the FTO gene have impaired satiety responsiveness and overconsumption. Also, Benedict et al. performed an analysis of the cross-sectional data from the Prospective Investigation of the Vasculature in Uppsala Seniors, reporting that some alleles of FTO may cause obesity by shifting the endocrine balance from leptin, the satiety hormone, to ghrelin, the hunger-promoting hormone [
46]. Furthermore, another study reported that men with the risk alleles of the FTO gene had less feelings of fullness and higher levels of hunger, food cravings, appetite, and prospective food consumption [
47].
The present study had some limitations as well. We conducted a cross-sectional study. Thus, the estimation of the causal relationship could not be identified. Moreover, several socioeconomic and cultural factors are involved in resistance to eating, while we only used a small sample size from two schools in Tehran. Therefore, the results of the present study cannot be generalized to other populations. Also, the present study investigated the rs9930506 polymorphism of the FTO gene. However, most other studies mentioned in the
discussion section evaluated the rs9939609 polymorphism of the FTO gene. Thus, these results might not be quite comparable. On the other hand, some previous studies had used self-reported questionnaires, which increased the chance of bias. Finally, cross-sectional studies simultaneously evaluate the exposure and outcome, which gives no evidence of a temporal relationship between them.
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