ANGPTL3 deficiency alters the lipid profile and metabolism of cultured hepatocytes and human lipoproteins

Even though the functions of ANGPTL3 in the circulation are relatively well characterized, many mechanistic questions regarding the molecular consequences of ANGPTL3 loss-of-function and protection against cardiovascular disease remain unanswered. To help understant the molecular mechanisms exerted by ANGPTL3 deficiency, we studied the alterations of ANGPTL3 loss-of-function in hepatocytes and plasma lipid molecular species profiles. Overall design: We characterized the impacts of ANGPTL3 depletion on the immortalized human hepatocyte (IHH) transcriptome, lipidome and human plasma lipoprotein lipidome. ANGPTL3 knock-down (KD) hepatocytes were created using an shRNA lentiviral vector. An approximately 90% KD efficiency was observed at shRNA and the KD effect was evident also at the protein level.