Seladelpar combined with complementary therapies improves fibrosis, inflammation, and liver injury in a mouse model of nonalcoholic steatohepatitis
Yun‐Jung Choi, Jeff Johnson, Jin-Ju Lee, Jiangao Song, Marcy Matthews, Marc K. Hellerstein, Charles A. McWherter
2023American Journal of Physiology-Gastrointestinal and Liver Physiology13 citationsDOIOpen Access PDF
Abstract
NASH is a chronic, progressive, and increasingly problematic liver disease that has been resistant to treatment with individual therapeutics. In this study using a diet-induced mouse model of NASH, we found that the PPARδ agonist seladelpar reduced fibrosis and NASH pathology alone and in combinations with a GLP-1-R agonist (liraglutide) or an ASK1 inhibitor (selonsertib). Liver transcriptome analysis comparing each agent and coadministration suggests seladelpar should be effective in combination with a variety of therapeutics.
Topics & Concepts
LiraglutideFibrosisAgonistSteatohepatitisNonalcoholic steatohepatitisMedicineInflammationNonalcoholic fatty liver diseaseLiver injuryDiseaseTranscriptomeFatty liverPharmacologyBioinformaticsInternal medicineReceptorBiologyEndocrinologyType 2 diabetesDiabetes mellitusGene expressionGeneBiochemistryLiver Disease Diagnosis and TreatmentPeroxisome Proliferator-Activated ReceptorsDrug Transport and Resistance Mechanisms