Diacylglycerol O-acyltransferase 2 (DGAT2) and Apolipoprotein B-100 (APOB100) regulatory machinery (DGAT2-APOB100 complex)

The Diacylglycerol O-acyltransferase 2 (DGAT2) and Apolipoprotein B-100 (APOB100) regulatory machinery is a specialized functional complex within the endoplasmic reticulum of hepatocytes that coordinates the final step of triglyceride synthesis with the assembly of very-low-density lipoprotein (VLDL) particles (Choi et al., 2013, PMID: 24014574). DGAT2 is an integral membrane enzyme that catalyzes the covalent attachment of a fatty acyl-CoA to diacylglycerol; its physical interaction with APOB100 ensures that newly synthesized triglycerides are efficiently loaded onto the nascent lipoprotein (Yen et al., 2008, PMID: 18757502). This machinery is a primary driver of hepatic lipid export and its overactivity is strongly linked to the development of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) (Wegner et al., 2018, PMID: 30139914). Pharmacological targeting of this machinery, particularly through DGAT2 inhibitors like ervogastat (PF-06865571), aims to reduce the triglyceride supply for VLDL assembly, thereby decreasing both liver fat content and circulating atherogenic lipoproteins (Calle et al., 2021, PMID: 34138804). Additionally, antisense therapies targeting APOB100, such as mipomersen, disrupt the structural integrity of this machinery to lower plasma lipid levels, although they carry a risk of increasing hepatic steatosis by trapping lipids within the liver (Akdim et al., 2010, PMID: 20153372).

Other names

DGAT2-APOB100 interactionVLDL assembly machineryHepatic VLDL regulatory complexDGAT2-APOB complex

Inhibition of DGAT2 enzymatic activity to reduce the triglyceride pool available for VLDL assembly and disruption of APOB100-mediated lipoprotein formation to decrease hepatic lipid export.