Fig. 1

Schematic diagram of lipid metabolism in NAFLD. The uptake of circulating fatty acids from chylomicron remnants or adipose tissue by FATP2/5 and CD36 leads to lipid accumulation in the liver. Fatty acid can take part in several pathways and transferred to the mitochondria and participate in β-oxidation (A). ACSL converts fatty acids to FA-CoA, which then enters the TAG synthesis pathway via chain reactions catalyzed by GPAT, AGPAT, PAP, and DGAT (B). Produced TAGs can be stored as LDs. PNPLA3, MBOAT7, and HSD17B13 are located on the surface of lipid droplets in hepatocytes. PNPLA3 catalyzes the hydrolysis of TG, MBOAT7 plays an important role during the noncanonical hepatic triglyceride synthesis pathway, and HSD17B13 appears to be involved in hepatic lipid biogenesis and metabolism (C). At the ER, TAGs can also be packaged into VLDL by MTTP and ApoB. TM6SF2 is also located in the ER and regulates VLDL secretion. Nascent VLDL particles packaged into VLDL transport vesicles are transported from the ER to the Golgi apparatus, and Apoc3, a component of VLDL, stimulates VLDL assembly and secretion. Finally, mature VLDLs are secreted through vesicle-mediated exocytosis (D)