Endurance Exercise Training Alleviates Hepatic Lipocalin‐2 Release and Prevents Anxiety‐Like Disorders in Chronically Stressed Mice

Abstract Exercise training can prevent anxiety disorders in both rodent models and human cohorts. The involvement of peripheral factors in exercise‐mediated mental health is being appreciated. It is recently shown that the hepatic biosynthesis of lipocalin‐2 (LCN2) can respond to chronic restraint stress (CRS) and elicit anxiety‐like behaviors via inhibiting the neural activity in the medial prefrontal cortex (mPFC). Here, it is found that 14‐day treadmill exercise training ameliorates anxiety‐like behaviors in these CRS‐treated mice. Further assays show that exercise intervention reduces the hepatic release of LCN2. Meanwhile, exercise training may also counteract the adverse effect of LCN2 via relieving the cortical microglial cell proliferation. The results collectively suggest that exercise training may modulate the liver‐brain axis to reshape the cortical activity for preventing anxiety disorders.