MC4R Variant Is Associated With BMI but Not Response to Resistance Training in Young Females

Abstract

Recently, a genome-wide association study (GWAS) that identified eight single-nucleotide polymorphisms (SNPs) associated with BMI highlighted a possible neuronal influence on the development of obesity. We hypothesized these SNPs would govern the response of BMI and subcutaneous fat to resistance training in young individuals (age = 24 years). We genotyped the eight GWAS-identified SNPs in the article by Willer et al. in a cohort (n = 796) that undertook a 12-week resistance-training program. Females with a copy of the rare allele (C) for rs17782313 (MC4R) had significantly higher BMIs (CC/CT: n = 174; 24.70 ± 0.33 kg/m2, TT: n = 278; 23.41 ± 0.26 kg/m2, P = 0.002), and the SNP explained 1.9% of overall variation in BMI. Males with a copy of the rare allele (T) for rs6548238 (TMEM18) had lower amounts of subcutaneous fat pretraining (CT/TT: n = 65; 156,534 ± 7,415 mm3, CC: n = 136; 177,825 ± 5,139 mm3, P = 0.019) and males with a copy of the rare allele (A) for rs9939609 (FTO) lost a significant amount of subcutaneous fat with exercise (AT/AA: n = 83; −798.35 ± 2,624.30 mm3, TT: n = 47; 9,435.23 ± 3,494.44 mm3, P = 0.021). Females with a copy of the G allele for a missense variant in the SH2B1 (rs7498665) was associated with less change of subcutaneous fat volume with exercise (AG/GG: n = 191; 9,813 ± 2,250 mm3 vs. AA: n = 126; 770 ± 2,772 mm3; P = 0.011). These data support the original finding that there is an association between measures of obesity and a variant near the MC4R gene and extends these results to a younger population and implicates FTO, TMEM18, and SH2B1 polymorphisms in subcutaneous fat regulation.

Leptin and leptin receptor genetic variants associate with habitual physical activity and the arm body composition response to resistance training

“…Similarly, another FAMuSS study from our research consortium reported PPARα L162V associated with the subcutaneous fat response to RT, with men carrying the rare allele gained considerably greater adiposity following unilateral resistance arm (Uthurralt et al 2007). Our previous reports (Orkunoglu-Suer et al 2011; Uthurralt, Gordish-Dressman, Bradbury, Tesi-Rocha, Devaney, Harmon, Reeves, Brandoli, Hansen, Seip, Thompson, Price, Angelopoulos, Clarkson, Moyna, Pescatello, Visich, Zoeller, Gordon, and Hoffman 2007) in combination with the present findings suggest that an interaction may exist between genetic profile and the body composition response to RT. Individuals who RT, with a certain genetic profile, may lead to poorer body composition response outcomes and limited localized exercise may trigger an increase in adiposity.…”

“…Our research group has observed that a missense mutation in the SH2b1 gene (rs7498665) resulted in women with the rare allele gaining more subcutaneous fat than women with two copies of the common allele (Orkunoglu-Suer et al 2010). Similarly, another FAMuSS study from our research consortium reported PPARα L162V associated with the subcutaneous fat response to RT, with men carrying the rare allele gained considerably greater adiposity following unilateral resistance arm (Uthurralt et al 2007).…”

Obesity-related Genetic Variants And Their Associations With Physical Activity

“…The limbic system is implicated in the control of food procurement as an evolutionarily conserved survival mechanism to defend against famine [36]. In this regard, these three GIANT consortium identified GWAS obesity SNPs that we found to be associated with physical activity and Orkunoglu-Suer et al found to be associated with body composition phenotypes [20] have been classified as hyperphagic genes related to appetite suppression and satiety whose regulation resides in the dopaminergic projection from the limbic system [37][38][39]. Recent research in animals suggests that the 'pleasure-reward' system residing in the dopaminergic pathway that regulates appetite and satiety has a key role in voluntary movement [25,40] and heightened reward sensitivity in animals with obesity that binge eat [41,42].…”

“…The sample consisted of healthy, young EuropeanAmerican men and women (Table 2) with a BMI level that reflected the larger FAMuSS cohort [20,26], and the general age-matched population from which they were recruited [1]. While age did not differ by sex (p > 0.05), men had a higher BMI than women (p < 0.001).…”

“…In our previous work [20] and that of others [15,[17][18][19], the effect-medication of physical activity on genetic predispositions for overweight and obesity was examined. What was not investigated using this approach is the possibility of obesity-related SNPs influence physical activity behavior (Fig.…”