Endurance training and essential amino acid intervention synergize to ameliorate fructose-induced metabolic dysfunction in mice

Abstract

Purpose: Excessive fructose (FRU) consumption can rapidly produce multiple features of metabolic syndrome, including dysregulation of systemic metabolism, insulin resistance, and diabetes. Essential amino acids (EAAs) and endurance exercise training (ET) improve abnormal metabolism in various disease conditions, yet their combined effect and metabolic mechanism remain unclear. Thus, the current study aimed to investigate metabolic kinetic mechanism and the combined effect of EAA and ET on fructose-induced metabolic dysfunction. Materials and methods: Mice were randomly divided into 5 groups with an 8-week intervention: normal chow (CON), FRU, FRU+ET, FRU+EAA or FRU+ET+ EAA, followed by stable isotope tracer infusions ([U-13C16]palmitate, [D2]glucose, and [D5]glycerol) or D2O administration to determine substrate metabolic flux rates and their contribution to TCA cycle flux and protein synthesis rates of various organs, respectively. Summary of results: FRU-induced adverse changes in body weight and physical function were reversed by ET, EAA, or ET+EAA. In stable isotope tracing analysis, ET and ET+EAA alleviated hyperglycemia by suppressing hepatic glucose production rate, while EAA and ET+EAA normalized palmitate turnover and contribution to TCA cycle in various organs. Additionally, the altered protein synthesis measured using a D2O labeling method was normalized by ET and ET+EAA. Conclusion:These findings suggest that the combined treatment of dietary EAAs and ET more effectively mitigates fructose-induced metabolic dysfunction by normalizing hepatic glucose production rate, protein synthesis rates, and fatty acid metabolism. This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI22C2208), and the National Research Foundation of Korea (NRF), funded by the Korea government (MSIT) (No. 2021R1A2C3005801), and partially funded by MYOCARE INC. 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.