Metabolomics revealed the anxiety-like behaviors led to liver injury through EGFR/PI3K/AKT/NF-κB pathway in rats

Abstract

Abstract Psychological distress is associated with increased liver disease mortality. This association highlighted the close relationship between psychological and physical health. Thus, further work to elucidated the underlying mechanism should be carried out. In this experiment, a model of anxious rats was established by compound stress. The HPA axis situation and inflammatory factor changes in the brain of the rats were observed, which in turn were evaluated for behavioral tests and liver function, respectively. The liver metabolic profiles of the rats were characterized by liquid chromatography-mass spectrometry (LC-MS). Differential metabolites were screened by p < 0.05 and VIP > 1. Pathway enrichment analysis was performed on metabolomics data by Ingenuity Pathway Analysis (IPA). Immunofluorescence (IF), immunohistochemistry (IHC) and western blotting, were employed to detect the expression of the screened target epidermal growth factor receptor (EGFR), and verify its potential pathway of mechanism. The results show that we found liver function impairment in anxiety-like rats. Further, 61 differential metabolites in control and anxiety groups were screened by using metabolomics (p < 0.05, VIP > 1). IPA analysis revealed the key target EGFR which was also identified from the HPA axis. We further found that anxiety-like rats may cause liver injury through EFGR/PI3K/AKT/NF-κB pathway, and then lead to the production of inflammatory factors in the liver. This study demonstrated that the activation of HPA axis in anxiety-like rats led to phosphorylation of EGFR, which finally contributed to liver injury through the EGFR/PI3K/AKT/NF-κB pathway. This finding provided novel evidence for the deleterious effects of psychological problems on physical health.