Very-low-density lipoprotein particle formation and secretion

Very-low-density lipoprotein (VLDL) particle formation and secretion is a complex metabolic process in the liver responsible for the assembly and release of triglyceride-rich lipoproteins into the systemic circulation. The pathway begins with the synthesis of apolipoprotein B-100 (ApoB-100), which serves as the essential structural scaffold for the particle, followed by the stepwise addition of lipids facilitated by the microsomal triglyceride transfer protein (MTTP). Dysregulation of this process, typically resulting in excessive VLDL output, is a central driver of hypertriglyceridemia and the subsequent generation of atherogenic low-density lipoproteins (LDL), which are major risk factors for cardiovascular disease. Pharmacological agents such as lomitapide and mipomersen target this pathway by inhibiting MTTP activity or suppressing ApoB synthesis, respectively, to reduce lipid levels in patients with severe dyslipidemia. However, a primary therapeutic challenge of inhibiting VLDL secretion is the resulting accumulation of lipids within hepatocytes, which can lead to hepatic steatosis and potential liver injury.

Other names

Very-low-density lipoprotein assembly and secretionVLDL secretionVLDL biogenesisHepatic VLDL productionVLDL assembly

Drugs targeting this process primarily act through the inhibition of the microsomal triglyceride transfer protein (MTTP) to prevent lipid loading of nascent lipoproteins, or via antisense oligonucleotides that inhibit the translation of apolipoprotein B (ApoB) mRNA.