Angiopoietin-like protein 8 (ANGPTL8) (ANGPTL8)

Angiopoietin-like protein 8 (ANGPTL8), also known as betatrophin or lipasin, is a liver-secreted protein that plays a critical role in regulating lipid metabolism by inhibiting lipoprotein lipase (LPL) activity (UniProt Q6UXH0). It functions primarily in the fed state, forming a complex with ANGPTL3 to suppress LPL in adipose and muscle tissues, thereby directing the storage of circulating triglycerides (PubMed: 31413171). Elevated levels of ANGPTL8 are strongly associated with hypertriglyceridemia and increased risk of cardiovascular disease (PubMed: 22822213). As a therapeutic target, the ANGPTL8 mRNA is specifically addressed using RNA interference (siRNA) technologies to prevent the translation of the protein (Arrowhead Pharmaceuticals). By reducing ANGPTL8 expression, these therapies aim to restore LPL activity, significantly lowering plasma triglycerides and non-HDL cholesterol in patients with severe dyslipidemia (ClinicalTrials.gov: NCT04832971). This approach offers a promising strategy for managing metabolic disorders and reducing the risk of acute pancreatitis associated with high triglyceride levels.

Other names

BetatrophinLipasinRIFLC19orf80Hepatocellular carcinoma-associated protein TD26Re-feeding induced fat and liver protein

RNA interference (siRNA) mediated degradation of ANGPTL8 mRNA to inhibit protein translation and increase lipoprotein lipase activity; monoclonal antibody-based inhibition of the ANGPTL8 protein.