Effects of Diet Quality and Psychosocial Stress on the Metabolic Profiles of Mice

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.