Modes-of-Action Related to Repeated Dose Toxicity: Tissue-Specific Biological Roles of PPARγ Ligand-Dependent Dysregulation in Nonalcoholic Fatty Liver Disease

Figure 4

Model of ligand-dependent PPARγ activation as a potential MIE for liver steatosis through CD36 mediated excessive FA uptake and consequent hepatic TG accumulation. (1): PPARγ-RXRα-heterodimer interacting with the PPARγ response elements (PPRE-N-PPRE) and transcriptional corepressor complex; (2): ligand-activated PPARγ-RXRα heterodimer with transcriptional coactivator complex and RNA pol II; (3): rough endoplasmic reticulum; (4): Golgi complex; (5): FAT/CD36 (fatty acid translocase); (6): plasma fatty acid binding protein (in blue) carrying fatty acid (in orange); (7): growing lipid droplet storing triglycerides and coated with LD associated proteins; (8): mitochondria; (9): bile canaliculus.