Temperature-dependent metabolite orchestration to acute submaximal exercise indicates cardiorespiratory fitness in humans

Cardiorespiratory fitness (CRF), an important biomarker of human health, is impaired in cold environment compared to thermoneutral condition. The study aimed to investigate the role of metabolome response to acute exercise in regulation of CRF at different ambient temperatures.A total of 27 young adults were recruited, and each subject underwent a cardiopulmonary exercise test (CPET) and a constant load submaximal exercise at both room temperature (25 °C) and cold temperature (0 °C). The serum samples were collected before and immediately after constant load exercise.Acute cold exposure decreased CRF by 41 %, accompanied by a metabolic shift to anaerobic respiration. It also decreased VO2 and increased respiratory quotient during constant load exercise. Metabolome profiling revealed that acute exercise reprogrammed serum metabolome in an ambient temperature-dependent manner. Specifically, exercise increased a cluster of fatty acids during cold exposure, possibly due to impaired fatty acid oxidation. The correlations between metabolite responses to acute exercise and exercise parameters were analyzed using partial least squares regression and machine learning, revealing that metabolite responses to acute exercise were highly correlated with exercise parameters and predictive of CRF. Among the contributors, tryptophan and its metabolites stood out as important ones.These results suggested that the metabolite responses to acute submaximal exercise unmasks the exercise performance at different ambient temperatures, highlighting the role of metabolite orchestration in the physiological regulation of CRF.