Key points are not available for this paper at this time.
Abstract Aerobic exercise enhances physiological performance by activating metabolic systems, including glucose oxidation and fat metabolism. Cellular glucose predominantly flows through glycolysis (95–98%), whereas a smaller fraction (2–5%) enters the hexosamine biosynthetic pathway (HBP), generating UDP‐ N ‐acetylglucosamine. Excessive carbohydrate intake and inactivity expedite glucose redirection toward the HBP via mass‐action mechanisms, which impair glucose uptake and insulin signalling. Although exercise intensity is a key determinant of fuel selection, with lipid oxidation predominating at moderate intensities (25–40% ) and glucose utilization becoming the primary energy source during vigorous activity (75–85% ), the mechanisms by which exercise intensity regulates HBP activity remain poorly understood. To investigate this, 12 male C57BL/6 mice were randomly assigned to control (CG, n = 6) and aerobic exercise groups (AEG, n = 6), with AEG undergoing 8 weeks of ‐based all‐out aerobic exercise (∼65.72% ). Untargeted plasma metabolomics was performed using ultra‐high performance liquid chromatography–time‐of‐flight mass spectrometry and processed using apLCMS, xMSanalyzer, xMSannotator, MetaboAnalyst 6.0 and the KEGG database. A two‐component partial least squares discriminant analysis model achieved 100% classification accuracy with strong explanatory and predictive performance ( R 2 = 0.981, Q 2 = 0.673). Eight N ‐acetyl compounds were significantly decreased in AEG compared with CG ( P = 0.0139; log 2 fold change = −1.17), corresponding to an approximate 0.445‐fold decrease in AEG relative to CG, with amino sugar and nucleotide sugar metabolism being the sole significantly affected pathway ( P = 0.0489). Four HBP intermediates ( N ‐acetyl‐ d ‐glucosamine 6‐phosphate, N ‐acetyl‐α‐ d ‐glucosamine 1‐phosphate, N ‐acetyl‐ d ‐mannosamine 6‐phosphate, N ‐acetyl‐α‐ d ‐galactosamine 1‐phosphate) showed discriminatory performance (AUC = 0.833). All‐out aerobic exercise suppresses HBP activity by lowering its key metabolic intermediates, suggesting a clear shift in glucose flux toward glycolysis. This metabolic redirection likely serves as a protective mechanism against the development of insulin resistance and diabetes.
Kang et al. (Thu,) studied this question.