CCL2 and CCR2 variants are associated with skeletal muscle strength and change in strength with resistance training

Abstract

Baseline muscle size and muscle adaptation to exercise are traits with high variability across individuals. Recent research has implicated several chemokines and their receptors in the pathogenesis of many conditions that are influenced by inflammatory processes, including muscle damage and repair. One specific chemokine, chemokine (C-C motif) ligand 2 (CCL2), is expressed by macrophages and muscle satellite cells, increases expression dramatically following muscle damage, and increases expression further with repeated bouts of exercise, suggesting that CCL2 plays a key role in muscle adaptation. The present study hypothesizes that genetic variations in CCL2 and its receptor (CCR2) may help explain muscle trait variability. College-aged subjects [n = 874, Functional Single-Nucleotide Polymorphisms Associated With Muscle Size and Strength (FAMUSS) cohort] underwent a 12-wk supervised strength-training program for the upper arm muscles. Muscle size (via MR imaging) and elbow flexion strength (1 repetition maximum and isometric) measurements were taken before and after training. The study participants were then genotyped for 11 genetic variants in CCL2 and five variants in CCR2. Variants in the CCL2 and CCR2 genes show strong associations with several pretraining muscle strength traits, indicating that inflammatory genes in skeletal muscle contribute to the polygenic system that determines muscle phenotypes. These associations extend across both sexes, and several of these genetic variants have been shown to influence gene regulation.

SLC30A8 Nonsynonymous Variant Is Associated With Recovery Following Exercise and Skeletal Muscle Size and Strength

“…Interestingly, this variant showed sexually dimorphic results: only males had an association in both cohorts, which is consistent with the previous EMD and FAMuSS cohorts (17,19), and additional articles showing the genetic influence on fitness phenotypic traits (24,25). This suggests that the sex-specific genetic architecture influencing phenotypes needs to be incorporated into the design of individualized exercise interventions to optimize results.…”

“…In addition, we wanted to compare and quantitate the genotype effect on an acute exercise intervention (single bout) versus a long-term 12-week resistance training intervention. Therefore, we included the following two different exercise cohorts: 1) Eccentric Muscle Damage (EMD) cohort allowed us to evaluate the effects of acute resistance exercise to exhaustion (16,17); and 2) the Functional Single Nucleotide Polymorphisms Associated with Muscle Size and Strength Study (FAMuSS) provided evaluation of a chronic resistance exercise program, a longitudinal 12-week resistance exercise training cohort (18,19). In this article, we demonstrated that two copies of the protective allele (TT) against the development of T2D are associated with a positive response to an acute resistance training exercise bout and show an association with pre-exercise measures of skeletal muscle size and strength.…”

“…All participants undertook 12 weeks of progressive resistance training using their nondominant arm only (18,19). Arm strength and skeletal muscle volume were measured before and after the training using maximal voluntary isometric contraction (MVC) and onerepetition maximum (1-RM) ( Supplementary Fig.…”

“…Arm strength and skeletal muscle volume were measured before and after the training using maximal voluntary isometric contraction (MVC) and onerepetition maximum (1-RM) ( Supplementary Fig. 1) (18,19). Upper arm skeletal muscle volume was quantified using magnetic resonance imaging (19).…”

Acute response of peripheral CCr5 chemoreceptor and NK cells in individuals submitted to a single session of low‐intensity strength exercise with blood flow restriction

“…On the other hand, chemokine receptors have an important effect on the mobilization of leucocytes and regulation of inflammatory response after strength exercise (Harmon et al, 2010;Jajtner et al, 2014). Due to the fact that exercise is a physiological stress and has similar immune responses to infections and sepsis (Walsh et al, 2011), we believe the CC chemokine receptor type 5 (CCR5), a protein found on the cell surface of many leucocytes attracted to infected tissues (Thomas, 2004), can be influenced by physical exercise sessions, especially of the strength training variation.…”