High-fat diet induces fibrosis in mice lacking CYP2A5 and PPARα: a new model for steatohepatitis-associated fibrosis
Xue Chen, George K. Acquaah-Mensah, Krista L. Denning, Jonathan M. Peterson, Kesheng Wang, James Denvir, Feng Hong, Arthur I. Cederbaum, Yongke Lu
2020American Journal of Physiology-Gastrointestinal and Liver Physiology13 citationsDOIOpen Access PDF
Abstract
PPARα is upregulated in cyp2a5 −/− mice, but HFD-induced steatosis is still deteriorated. PPARα abrogation makes cyp2a5 −/− mice more sensitive to HFD-induced steatosis, liver inflammation, and fibrosis, suggesting that PPARα upregulation in cyp2a5 −/− mice is a compensation response. HFD-induced liver inflammation, fibrosis, and nitrotyrosine formation in pparα −/− /cyp2a5 −/− mice are all within clusters of lipid droplets, and lipid droplets are all within CYP2E1-positive area.
Topics & Concepts
SteatosisInternal medicineLipid metabolismEndocrinologyPeroxisome proliferator-activated receptorFibrosisCYP2E1ChemistryKnockout mouseSteatohepatitisDownregulation and upregulationFatty liverBiologyReceptorMedicineMetabolismCytochrome P450BiochemistryGeneDiseaseLiver Disease Diagnosis and TreatmentPeroxisome Proliferator-Activated ReceptorsAlcohol Consumption and Health Effects