Front Endocrinol (Lausanne). 2026 Jun 26;17:1858091. doi: 10.3389/fendo.2026.1858091. eCollection 2026.
ABSTRACT
The liver-brain axis (LBA) represents a bidirectional communication network between the liver and the central nervous system (CNS), governed by integrated neural, humoral, and immune signaling pathways. Emerging evidence indicates that the liver functions not merely as a passive metabolic organ subordinate to central commands, but rather as a dynamic hub that actively senses and modulates peripheral neuroimmune responses. We here first delineate the fundamental communication mechanisms and the transport kinetics of signaling molecules governing LBA interactions. We then examine the profound species-specific disparities between humans and mice-particularly regarding signaling mediators, blood-brain barrier (BBB) architecture, and the hepatic immune microenvironment. From a pathophysiological perspective, we establish that LBA dysfunction serves as a core driver of obesity, diabetes, and their multisystemic sequelae, including cardiovascular diseases and psychiatric disorders such as anxiety and depression. Finally, we highlight recent therapeutic advances targeting the LBA for the management of metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), atherosclerosis, and associated psychiatric conditions, thereby underscoring the immense clinical potential of LBA-targeted interventions.
PMID:42434295 | PMC:PMC13349931 | DOI:10.3389/fendo.2026.1858091