ATF4-mediated CD36 upregulation contributes to palmitate-induced lipotoxicity in hepatocytes
Alexandra Griffiths, Jun Wang, Qing Song, Samuel Man Lee, José Córdoba‐Chacón, Zhenyuan Song
2023American Journal of Physiology-Gastrointestinal and Liver Physiology18 citationsDOIOpen Access PDF
Abstract
We provided the initial evidence that ATF4 is a principal transcription factor mediating hepatic CD36 expression in that both palmitate- and ER stress-elicited CD36 upregulation was blunted by ATF4 gene knockdown in hepatocytes, and hepatocyte-specific ATF4 knockout mice manifested lower hepatic CD36 expression. We further confirmed that the ATF4-CD36 pathway activation contributes to palmitate-induced hepatolipotoxicity as genetic inhibition of either ATF4 or CD36 alleviated cell death and intracellular triacylglycerol accumulation in response to exogenous palmitate exposure.
Topics & Concepts
ATF4CD36Downregulation and upregulationGene knockdownHepatocyteLipotoxicityEndocrinologyInternal medicineCell biologyChemistryBiologyApoptosisMedicineGeneIn vitroBiochemistryReceptorInsulin resistanceInsulinLiver Disease Diagnosis and TreatmentEndoplasmic Reticulum Stress and DiseasePeroxisome Proliferator-Activated Receptors