There has been an increasing interest in relationship between stress and diet. To address this relationship, we evaluated an animal model of depression: male C57BL/6J mice subjected to subchronic mild social defeat stress (sCSDS) for 10 consecutive days using male ICR mice under two different calorie-adjusted diets conditions-nonpurified (MF) and semipurified (AIN) diets made from natural and chemical ingredients mainly, respectively. Our previous study indicates that diet quality and purity affect stress susceptibility in sCSDS mice. We therefore hypothesized that there are some key peripheral metabolites to change stress-susceptible behavior. GC-MS metabolomics of plasma, liver, and cecal content were performed on four test groups: sCSDS + AIN diet (n = 7), sCSDS + MF diet (n = 6), control (no sCSDS) + AIN diet (n = 8), and control + MF diet (n = 8). Metabolome analyses revealed that the number of metabolites changed by food was larger than the number changed by stress in all tissues. Enrichment analysis of the liver metabolite set altered by food implies that stress-susceptible mice show increased glycolysis-related substrates in the liver. We found metabolites that were affected by stress (e.g., plasma and liver 4-hydroxyproline and plasma beta-alanine are higher in sCSDS than in control) and a stress × food interaction (e.g., plasma GABA is lower in sCSDS + AIN than in sCSDS + MF). Because functional compounds were altered by both stress and food, diet may be able to attenuate various stress-induced symptoms by changing metabolites in peripheral tissues.
Keywords: chronic social stress; diet; metabolome; mouse; peripheral tissue; plasma.