PPARα agonist fenofibrate attenuates iron-induced liver injury in mice by modulating the Sirt3 and β-catenin signaling
Ashok Mandala, William J. Chen, A Austin, Milan Malhotra, Sanmathi Chavalmane, Kyle S. McCommis, Anping Chen, Danielle Carpenter, Pratim Biswas, Jaya P. Gnana‐Prakasam
2021American Journal of Physiology-Gastrointestinal and Liver Physiology25 citationsDOIOpen Access PDF
Abstract
Hepatic intracellular iron accumulation has been implicated in the pathophysiology of chronic liver diseases. In this study, we identified a novel mechanism involved in the progression of fibrosis. Excess iron accumulation in liver caused downregulation of PPARα-Sirt3-Wnt signaling leading to fibrosis. This work has significant translational potential as PPARα agonist fenofibrate could be an attractive therapeutic drug for the treatment of liver disorders associated with iron overload.
Topics & Concepts
FenofibrateAgonistDownregulation and upregulationPeroxisome proliferator-activated receptorPathophysiologyFibrosisHepatic fibrosisEndocrinologySignal transductionMedicineInternal medicineCancer researchChemistryPharmacologyReceptorBiochemistryGeneEndoplasmic Reticulum Stress and DiseasePeroxisome Proliferator-Activated ReceptorsLiver Disease Diagnosis and Treatment