Metabolomics Investigation of a Multi‐Ingredient Supplements‐Modulated Changes in Metabolism in Mice After Endurance Exercise

Energy metabolism manipulation strategy, enhancing fat metabolism while reducing the dependence on glucose, is beneficial to improve exercise performance. The multi-ingredient supplements (MIS) mixed with valine, isoleucine, leucine, β-alanine, creatine, L-carnitine, quercetin, and betaine were found to be able to improve the endurance performance of mice, which was associated with a shift of energy substrates from glucose to fatty acids. Thus, we hypothesized that the MIS regulating lipid metabolism contributes to enhancing exercise endurance in mice. The present study aimed to explore the alterations in the biochemical composition of mice treated with the MIS using a metabolomics strategy after they were subjected to endurance exercise. The serum metabolite profile was investigated using ultrahigh performance liquid chromatography tandem mass spectrometry. Results showed that significant changes in lipid metabolism were observed in the MIS-treated mice during endurance exercise compared with the vehicle control. Specifically, the MIS treatment reduced glycerophospholipids, glycerolipids, long-chain fatty acids, and inflammatory signaling arachidonic acid derivatives, and increased medium-long-chain acylcarnitine levels relative to the exercised group. Furthermore, the levels of dimethylglycine (DMG), citrate (CA), glycerol, creatine, and corticosterone were also increased after the MIS supplementation, which was associated with the changes in the pathways of serotoninergic synapses, CA cycles, and amino acid metabolisms. In conclusion, the MIS tested in this study effectively alters serum metabolomics profiles, which provides further evidence to support a shift in energy substrate utilization contributing to the ability of the MIS to improve exercise performance.