Purpose:
Cardiovascular fitness (maximal oxygen uptake [VO₂max]) is linked with health indicators and the α2 subunit of the AMP-activated protein kinase (AMPKα2), encoded by the PRKAA2 gene, is an important metabolic sensor and can mediate part of exercise effect. It has been proposed that changes in the metabolic process bound with exercise might occur through epigenetic regulations. However, how VO₂max can influence the epigenetic mechanism and consequently health is still unknown. The aim of this study was to investigate the PRKAA2 gene methylation profile and its relation to metabolic variables in normoglycemic monozygotic twins discordant for VO₂max.

Methods:
Nine pairs of monozygotic twins were studied, with the intra-pair VO₂max difference >10 ml • kg^–1 • min^–1. An oral glucose tolerance test was used, and blood samples were collected for biochemical and DNA methylation analyses.

Results:
No DNA methylation differences were observed between the groups. The low-cardiorespiratory-fitness group demonstrated a positive correlation between the methylation profile and low-density lipoprotein (CpG1, r = 0.714) and total cholesterol (CpG1, r = 0.723; CpG3, r = 0.678). Only the high-cardiorespiratory-fitness group showed correlations between glucose and insulin variables.

Conclusions:
Our data suggest a link between high cardiorespiratory fitness and glucose-insulin correlation. The results provide important insights for future studies about the mechanisms through which VO₂max can influence glucose metabolism.