Serum metabolomic responses to aerobic exercise in rats under chronic unpredictable mild stress

This study analyzed the effects of aerobic exercise on endogenous serum metabolites in response to chronic unpredictable mild stress (CUMS) using a rat model, aiming to identify the metabolic regulatory pathways involved in the antidepressant effect resulted from a 28-day treadmill aerobic exercise intervention. The animals were randomly divided into four groups (n = 8): normal control, normal with aerobic exercise, CUMS control, and CUMS with aerobic exercise. Body weight, sucrose preference and open field tests were performed weekly during the intervention period for changes in depressant symptoms. Serum metabolic profiles obtained by using the LC–MS/MS metabolomics were analyzed to explore the regulatory mechanism for the effect of the aerobic exercise on depression. Behavior tests showed that the aerobic exercise resulted in a significant improvement in depression-like behavior in the CUMS rats. A total of 21 differential metabolites were identified as being associated with depression in serum metabolic profile, of which the aerobic exercise significantly modulated 15, mainly related to amino acid metabolism and energy metabolism. Collectively, this is the first study that LC–MS/MS techniques were used to reveal the modulatory effects of aerobic exercise on the serum metabolic profile of depressed rats and the findings further enriched our understanding of potential mechanisms of aerobic exercise interventions on depression.