**1. Introduction**

Obesity is defined as excessive body weight gain due to an increased accumulation of body fat that presents a leading cause of the largest public health problems [1], since nearly 40% of adults are overweight and 10–15% are obese worldwide [2]. Obesity phenotypes are associated with a higher risk of many medical problems such as cardiovascular events, metabolic disorders, type 2 diabetes, neuropsychiatric disorders, and some types of cancer, the majority of which can lead to elevated mortality risk [3–6]. An analysis of the latest work in the literature has shown that modifiable factors positively affect our well-being and health. The best effect can be achieved by combining positive actions in the field of diet, supplementation, moderate but systematic physical activity, and adding the right amount of sleep per day [7,8].

**Citation:** Maculewicz, E.; Leo ´nska-Duniec, A.; Mastalerz, A.; Szarska, E.; Garbacz, A.; Lepionka, T.; Łakomy, R.; Anyzewska, A.; ˙ Bertrandt, J. The Influence of *FTO, FABP2, LEP, LEPR,* and *MC4R* Genes on Obesity Parameters in Physically Active Caucasian Men. *IJERPH* **2022**, *19*, 6030. https://doi.org/10.3390/ ijerph19106030

Academic Editors: David Berrigan and Paul B. Tchounwou

Received: 9 March 2022 Accepted: 12 May 2022 Published: 16 May 2022

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**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

Obesity is a complex multifactorial disease that has a well-confirmed strong genetic basis but needs behavioral, developmental, and/or environmental influences to develop [1,9,10]. Several studies have demonstrated the role of lifestyle, including caloric intake and physical activity level, in the regulation of body weight [11,12]. However, the problem still lies in identifying the genes and polymorphic sites related to obesity and describing the biological mechanisms by which they exert their effects [9].

Although studies of the common obesity genetics were determined by genome-wide association studies (GWASs), this stage was set by research on monogenic obesity, which emphasized that the leptin–melanocortin signaling pathway is the major regulator of food intake. Several genes involved in the development of monogenic obesity are in or near loci subsequently linked by GWASs with obesity-related traits. To date, over 600 genes and chromosomal regions have been associated with the regulation of body weight and composition [9,13]. The genetic risk of common obesity is linked to the accumulation of numerous loci, each contributing a small part of the total obesity risk [9]. Therefore, the analysis of haplotypes and interactions between candidate genes are more informative than methods based on individual signal-nucleotide polymorphism (SNP) and might give additional information important for understanding complex interactions between various gene variants [14,15]. Consequently, in our study, we decided to analyze five of the most promising polymorphic sites localized within obesity-related genes: fat mass and obesityassociated (*FTO*), fatty acid-binding protein 2 (*FABP2*), leptin (*LEP*), leptin receptor (*LEPR*), and melanocortin-4 receptor (*MC4R*), which are characterized in Table 1 [9,16–22]. The genes were selected based on a literature review and our own previous studies. Recently, studies have confirmed that these SNPs are linked to obesity-related traits such as BMI, hip circumference, total body weight, body fat percentage, and cardiometabolic traits, among others. The noted associations are replicable across different ethnic populations as well as various age groups [9,13,16–22]. Guilherme et al. (2019) suggested that SNPs, which can affect body composition parameters, might influence physical performance [23].

**Table 1.** Characteristics of the studied genes and polymorphic sites.


The above-mentioned findings highlight the selected genes' association with body mass and body composition parameters. However, the results are inconsistent and the interactions between these candidate genes are still unknown. Thus, this study aimed to examine the associations between *FTO* (rs9939609), *FABP2* (rs1799883), *LEP* (rs2167270), *LEPR* (rs1137101), and *MC4R* (rs17782313) polymorphisms and obesity-related traits. Therefore, we studied individually and in gene–gene interaction models the alleles and genotypes

distribution in a group of physically active Caucasian men measured for selected body mass and body composition traits.

#### **2. Materials and Methods**
