Hepatic triglyceride synthesis and very low-density lipoprotein production pathway

The hepatic triglyceride synthesis and very low-density lipoprotein (VLDL) production pathway is a central metabolic process that regulates the export of lipids from the liver to peripheral tissues [1]. This pathway involves the de novo synthesis of fatty acids, their esterification into triglycerides by enzymes such as diacylglycerol O-acyltransferase 1 and 2 (DGAT1/2), and the subsequent assembly of these lipids into VLDL particles [1, 4]. The assembly process is mediated by microsomal triglyceride transfer protein (MTP), which loads triglycerides onto apolipoprotein B-100 (ApoB-100) before the mature VLDL is secreted into the circulation [2, 5]. Dysregulation of this pathway, often characterized by excessive triglyceride production or impaired secretion, is a primary driver of non-alcoholic fatty liver disease (NAFLD) and hypertriglyceridemia [3]. Pharmacological targeting of this pathway includes MTP inhibitors like lomitapide and ACC inhibitors like firsocostat, which aim to reduce lipid levels but must be carefully managed to avoid the accumulation of fat within the liver (steatosis) [2, 3].

Other names

Hepatic lipogenesis and VLDL secretionHepatic TG-VLDL axisDe novo lipogenesis and VLDL assembly

Inhibition of key enzymatic steps in fatty acid synthesis (e.g., ACC, FASN) or triglyceride esterification (e.g., DGAT2), and disruption of VLDL assembly or secretion (e.g., MTP, ApoB-100).