Exercise plays a beneficial role in the treatment of metabolic syndrome (MetS). Metabolomics can provide new insights and facilitate the optimization of exercise prescription. This study aimed to investigate whether the response of the human serum metabolic fingerprint to exercise depends on exercise mode or the presence of MetS. Twenty-three sedentary men (nine with MetS and fourteen healthy) completed four trials: Resting, high-intensity interval exercise (HIIE), continuous moderate-intensity exercise (CME), and resistance exercise (RE). Blood samples were collected pre-exercise, immediately after exercise, and 1 h post-exercise for targeted metabolomic analysis in serum by liquid chromatography–mass spectrometry. Time exerted the strongest differentiating effect, followed by exercise mode. The largest changes from baseline were found in the immediate post-exercise samples. RE caused the strongest responses overall, followed by HIIE, while CME had minimal effect. Unlike previous results in urine, no valid model could separate the two groups in serum. Exercise exerted a beneficial effect on prominent serum biomarkers of metabolic risks, such as branched-chain amino acids, alanine, acetylcarnitine, choline, and betaine. These findings contribute to the ongoing research efforts to map the molecular responses to exercise and to optimize exercise guidelines for individuals at cardiometabolic risk.

Life expectancy has risen in the past decades, resulting in an increase in the number of aged individuals. Exercise remains one of the most cost-effective treatments against disease and the physical consequences of aging. The purpose of this research was to investigate the effects of aging, long-term and lifelong exercise on the rat urinary metabolome. Thirty-six male Wistar rats were divided into four equal groups: exercise from 3 to 12 months of age (A), lifelong exercise from 3 to 21 months of age (B), no exercise (C), and exercise from 12 to 21 months of age (D). Exercise consisted in swimming for 20 min/day, 5 days/week. Urine samples collection was performed at 3, 12 and 21 months of life and their analysis was conducted by liquid chromatography-mass spectrometry. Multivariate analysis of the metabolite data did not show any discrimination between groups at any of the three aforementioned ages. However, multivariate analysis discriminated the three ages clearly when the groups were treated as one. Univariate analysis showed that training increased the levels of urinary amino acids and possibly protected against sarcopenia, as evidenced by the higher levels of creatine in the exercising groups. Aging was accompanied by decreased levels of urinary amino acids and signs of increased glycolysis. Concluding, both aging and, to a lesser degree, exercise affected the rat urinary metabolome, including metabolites related to energy metabolism, with exercise showing a potential to mitigate the consequences of aging.