Hepatic very-low-density lipoprotein production (Hepatic VLDL production)

Hepatic very-low-density lipoprotein (VLDL) production is the multi-step biological process by which hepatocytes assemble and secrete triglyceride-rich lipoprotein particles into the systemic circulation [1, 2]. This process is essential for the transport of endogenously synthesized lipids from the liver to peripheral tissues, but its overactivity is a primary driver of atherogenic dyslipidemia [13, 15]. The biogenesis of VLDL involves the translation of its structural protein, Apolipoprotein B-100 (ApoB), and the subsequent loading of neutral lipids onto this protein by the Microsomal Triglyceride Transfer Protein (MTP) [1, 9, 11]. Drugs such as Lomitapide, an MTP inhibitor, and Mipomersen, an ApoB-targeted antisense oligonucleotide, are used to treat severe hyperlipidemias by directly reducing the output of VLDL from the liver [1, 8]. While effective at lowering plasma lipids, these therapies carry a significant risk of causing hepatic steatosis, as inhibited VLDL secretion leads to the sequestration of triglycerides within the liver [1, 7, 17]. This target entry represents a physiological pathway rather than a single molecular target, but it serves as a critical focus in the development of cardiometabolic therapies [13].

Other names

Hepatic VLDL secretionHepatic VLDL assemblyVLDL biogenesisHepatic lipoprotein synthesis

Inhibition of microsomal triglyceride transfer protein (MTP), inhibition of apolipoprotein B-100 (ApoB) synthesis via antisense oligonucleotides, or modulation of regulatory proteins like ANGPTL3 and ApoC-III that influence VLDL assembly and clearance.