Improvement on central nervous fatigue by diglyceride-based food for special medical purposes in a chronic stress-induced mouse model

As a natural component of edible oils, diglyceride has attracted attention for its anti-obesity, anti-inflammation and neuroprotective potential. However, the anti-fatigue effects of the diglyceride-based food for special medical purposes (DIG-FSMP) were not reported. In this study, in silico analysis was firstly used to search the link between diglyceride (DIG) and fatigue. Subsequently, 50 male Institute of Cancer Research (ICR) mice (n=10/group) were were subjected to a 28-day intervention with DIG-FSMP or Rhodiola rosea (positive control). Neurotransmitter levels (GABA and Glu) and differential gene expression were quantified in harvested brain and hippocampal tissues to evaluate the anti-central fatigue effects. The results showed that 48 potential anti-central fatigue targets of diglyceride were identified. Among them, PRKCA, PPARG, and ALOX5 are the core anti-fatigue targets reported in literature, suggesting that DIG-FSMP has potential anti-central fatigue activity. Animal experiments demonstrated that compared with the model group, after DIG-FSMP intervention, the content of GABA in mice decreased by 29% and the content of Glu increased by 9%; in the open field test, the number of grid-crossings increased by 31% and the number of cheek-scratching increased by 72%. RNA-Seq analysis identified 340 differentially expressed genes (DEGs) in high-dose group relative to model group. In particular, 3 of the in silico identified targets are indeed differentially expressed genes in M and H groups: TLR2，Nr4a1 and Nr4a2. Gut microbiota analysis indicated that at the genus level, a significant increase ( unclassified Bacteroidetes and Lactobacillus ) (p<0.05) and a significant decrease ( Akkermansia ) (p<0.05)were observed in H group, compared with M group. DIG-FSMP effectively ameliorates central nervous fatigue by restoring behavioral vitality, balancing GABA/Glu levels, and modulating brain gene expression and gut microbiota composition. However, further research is needed to determine the optimal dosage of DIG-FSMP fighting against central nervous fatigue.