Potential Physiological Convergence Between GLP-1 Receptor Signaling and Hepatocyte TAZ in Metabolic Liver Disease: From Metabolic Homeostasis to Fibrotic Remodeling.
- 1King Abdullah International Medical Research Center, Jeddah 21423, Saudi Arabia.
- 2Department of Basic Medical Sciences, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Jeddah 21423, Saudi Arabia.
- 3Ministry of the National Guard-Health Affairs, Jeddah 21423, Saudi Arabia.
Abstract
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.
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BibTeX
@article{gholam2026potential,
title = {{Potential Physiological Convergence Between GLP-1 Receptor Signaling and Hepatocyte TAZ in Metabolic Liver Disease: From Metabolic Homeostasis to Fibrotic Remodeling.}},
author = {Mohammed F Gholam},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15191813},
url = {https://europepmc.org/article/MED/42882511},
note = {CC BY},
}
RIS
TY - JOUR
TI - Potential Physiological Convergence Between GLP-1 Receptor Signaling and Hepatocyte TAZ in Metabolic Liver Disease: From Metabolic Homeostasis to Fibrotic Remodeling.
AU - Mohammed F Gholam
PY - 2026
DA - 2026/10/04
JO - Cells
DO - 10.3390/cells15191813
UR - https://europepmc.org/article/MED/42882511
AB - 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.
SN - 2073-4409
ER -