Potential Physiological Convergence Between GLP-1 Receptor Signaling and Hepatocyte TAZ in Metabolic Liver Disease: From Metabolic Homeostasis to Fibrotic Remodeling

Metabolic dysfunction-associated steatotic liver disease (MASLD) progresses when nutrient excess, insulin resistance, adipose dysfunction, and hepatocellular stress overwhelm hepatic adaptation. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve weight, glycemic control, and steatohepatitis, and semaglutide has demonstrated histological improvement in metabolic dysfunction-associated steatohepatitis (MASH). In parallel, the transcriptional coactivator with PDZ-binding motif (TAZ; WWTR1) has emerged as a nutrient-, cholesterol-, and mechanics-responsive regulator linking stressed hepatocytes to inflammation and fibrogenesis through Hippo-YAP/TAZ signaling and Indian hedgehog. This narrative review integrates incretin physiology with cell-specific TAZ biology across the gut–brain–axis, adipose tissue, pancreatic islets, liver sinusoidal endothelial cells, hepatocytes, immune cells, and hepatic stellate cells. Recent evidence that semaglutide can signal through intrahepatic sinusoidal endothelial GLP-1 receptors provides a weight-loss-independent route to reduced hepatic inflammation and fibrosis; however, it does not establish that TAZ is a downstream mediator. The evidence therefore supports a multilevel convergence model in which GLP-1RAs lower metabolic and inflammatory inputs that favor TAZ activation, while direct GLP-1RA-to-TAZ signaling remains a testable hypothesis. Receptor-validated, cell-specific, weight-controlled, and longitudinal human studies are needed to distinguish mediation from parallel response and to determine whether TAZ-pathway biomarkers can guide mechanism-based therapy.