Characterization of an in vitro steatosis model simulating activated de novo lipogenesis in MAFLD patients

Abstract

Activated de novo lipogenesis (DNL) is the critical pathway involved in the progression of metabolic-associated fatty liver disease (MAFLD). We present an invitro steatosis model for MAFLD that induces steatosis through activated DNL. This model utilizes insulin and LXR receptor ligand T0901317, eliminating the need for fatty acid treatment. Significant increases in triglycerides (TAGs) and expression of DNL-related transcription factors were observed. Transcriptomic analysis revealed distinct gene expression profiles between the DNL and conventional oleic acid (OA)-induced steatosis model. DNL steatosis model exhibited elevated pathways related to glycolysis, cholesterol homeostasis, and bile acid metabolism, reflecting its clinical relevance to MAFLD. Moreover, C75 and JNK-IN-5A compounds effectively reduced TAG accumulation and steatosis-related protein expression in the DNL model, whereas they had no significant impact on TAG accumulation in the OA model. In conclusion, we introduce an ideal model for steatosis study, which could help in understanding the MAFLD mechanisms.