Human Apolipoprotein C3 (APOC3) Protein

Background

APOC3 is a critical regulator of triglyceride-rich lipoprotein (TRL) metabolism, primarily associated with VLDL, HDL, and chylomicrons. APOC3 inhibits lipoprotein lipase (LPL) and hepatic uptake of remnant lipoproteins by interfering with the binding of TRLs to heparan sulfate proteoglycans (HSPG) and the low-density lipoprotein receptor (LDLR). Elevated APOC3 levels are strongly associated with hypertriglyceridemia, atherogenic dyslipidemia, and increased risk of cardiovascular disease. APOC3 expression is regulated by dietary factors, insulin, and nuclear receptors such as PPAR-alpha. Loss-of-function mutations in the APOC3 gene result in lower plasma triglycerides and reduced cardiovascular risk, highlighting its potential as a therapeutic target for lipid disorders. APOC3 also modulates inflammatory responses and has been implicated in non-alcoholic fatty liver disease (NAFLD), where elevated levels contribute to hepatic lipid accumulation. Pharmacological inhibitors of APOC3, such as antisense oligonucleotides, are being developed to lower plasma triglycerides and improve lipid profiles in hyperlipidemic patients.