Hepatic very-low-density lipoprotein (VLDL) synthesis and secretion machinery (VLDL synthesis and secretion machinery)

The hepatic very-low-density lipoprotein (VLDL) synthesis and secretion machinery is the integrated biological system responsible for the assembly, maturation, and export of triglyceride-rich lipoproteins from hepatocytes into the bloodstream. This multi-step process involves the synthesis of apolipoprotein B-100 (ApoB-100), its co-translational lipidation by microsomal triglyceride transfer protein (MTP), and the subsequent expansion of the lipid core through the addition of triglycerides, a process facilitated by enzymes such as diacylglycerol O-acyltransferase 2 (DGAT2). Once assembled, the nascent VLDL particles are transported via specialized vesicles to the Golgi apparatus for final processing before being secreted into the space of Disse. This machinery is a critical regulator of systemic lipid homeostasis; its overactivity, often associated with insulin resistance and obesity, leads to hypertriglyceridemia and increased risk of atherosclerotic cardiovascular disease. Therapeutic strategies targeting this machinery include MTP inhibitors like lomitapide and ApoB-100 antisense oligonucleotides like mipomersen, which effectively lower plasma lipids but are associated with the risk of hepatic steatosis due to the retention of lipids within the liver.

Other names

VLDL assembly and secretion pathwayHepatic VLDL production machineryApolipoprotein B-containing lipoprotein assembly systemVLDL biogenesis machinery

Inhibition of microsomal triglyceride transfer protein (MTP), antisense inhibition of apolipoprotein B-100 (ApoB-100) mRNA, inhibition of diacylglycerol O-acyltransferase 2 (DGAT2), and inhibition of angiopoietin-like 3 (ANGPTL3).