Chronic Stress Induces Hepatic Steatosis via Brain-Hepatic Sympathetic Axis Mediated Catecholamine Resistance.

ABSTRACT: Chronic stress is epidemiologically linked to metabolic dysfunction-associated steatotic liver disease (MASLD), yet the underlying mechanisms remain unclear. In mice exposed to chronic restraint stress (CRS), we observed weight-independent hepatic steatosis with marked degeneration of sympathetic fibers. Stress elevated circulating norepinephrine levels but blunted hepatic β-adrenergic/cyclic adenosine monophosphate (cAMP) signaling accompanied by downregulation of β3-adrenergic receptor (β3-AR), indicating hepatic catecholamine resistance. Blocking hepatic sympathetic input prevented stress-aggravated steatosis and restored β-adrenergic signaling, whereas pharmacologic activation of β3-AR with mirabegron alleviated stress-induced lipid accumulation. Pseudorabies virus retrograde tracing a

SUBMITTER: Wu S 

PROVIDER: S-EPMC12837740 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature