García, Luis A.

Skeletal muscle is a highly plastic tissue, adapting its structure and metabolism in response to various stimuli like exercise. This study aimed to determine the plasticity of skeletal muscle DNA methylation in response to an acute exercise bout in volunteers with a range of insulin sensitivities. We studied 14 sedentary participants (7 male/7 female): age = 34.5 ± 3.1 years, body mass index = 29.3 ± 1.9 kg/m2 and HbA1c = 5.3 ± 0.1 %. We performed VO2peak tests to determine exercise capacity (VO2peak = 25.5 ± 1.6 mL per Kg per minute) and euglycemic hyperinsulinemic clamps (Rd value = 5.9 ± 0.8 mg per Kg per minute) with vastus lateralis muscle biopsies before and 30 minutes after a single 48-minute exercise bout. We extracted DNA from the muscle biopsies and performed reduced representation bisulfite sequencing. After performing quality control on the sequencing data, 1,034,947 sites were included for downstream analyses. MethylSig analysis revealed 17,030 differentially methylated cytosines (DMC), 9,020 increased and 8,010 decreased. To identify biologically meaningful DMCs, we used a mean change of >10%, which resulted in 1,179 and 1,436 increased and decreased sites, respectively. Pathway analysis of the increased DMCs revealed an enrichment in efferocytosis, leukocyte transendothelial migration, and FOXO-mediated transcription of oxidative stress pathways. In addition, pathway analysis of the decreased DMCs revealed an enrichment in metabolic (type 2 diabetes/ PI3K-Akt signaling), actin cytoskeleton, integrin/extracellular matrix and calcium signaling pathways. Our study reveals that an acute exercise bout induces alterations in the DNA methylation of skeletal muscle, impacting specific pathways in individuals with varying degrees of insulin sensitivity. Notably, our findings underscore the remarkable plasticity of skeletal muscle tissue. This research was funded by the National Institutes of Health, grant number R01DK094013 (Dawn Coletta). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The vitamin D receptor (VDR) is vital for maintaining calcium and phosphate balance and regulating bone metabolism. Recent research has suggested that VDR also plays an essential role in metabolic diseases. Previous studies on non-Hispanic whites have shown that VDR single nucleotide polymorphisms (SNP) are associated with cardiometabolic phenotypes. However, the association between VDR SNPs and cardiometabolic traits in Hispanics remains unclear. This study investigated the association between VDR SNPs and cardiometabolic phenotypic data in self-reported Hispanics (n = 1610) from the Arizona Insulin Resistance registry and Sangre Por Salud Biobank. The study population was predominantly female (66.4%) with a mean age of 40 ± 14 years (n = 121 <18 years) and an average body mass index (BMI) of 29.8 ± 6.3 kg/m2. We performed a genotyping association analysis of VDR SNPs (Taq1-rs731236, Fok1-rs2228570 and Apa1-rs7975232) with cardiometabolic traits using linear regression models. The results showed that Taq1 and Apa1 were strongly associated with systolic blood pressure (SBP) in children (<18 years), while Fok1 was associated with measures of adiposity, including fat mass, waist circumference, and BMI. In age-stratified adult (≥18 years) models, Taq1 was strongly associated with hemoglobin A1c, while Apa1 was associated with BMI and fasting glucose. Fok1 had no significant associations in the adult models. In conclusion, the VDR SNPs were associated with several cardiometabolic phenotypes in this Hispanic sample, but the type and strength of the associations varied by age group.