Abstract

Significance Here we show that ANGPTL8 plays a major role in the trafficking of triglycerides to peripheral tissues in response to food intake in mice. Circulating triglycerides are predominantly delivered to skeletal muscle and heart during fasting and are partitioned to adipose tissue upon refeeding. The postprandial increase in triglyceride delivery to adipose tissue is abolished in mice lacking ANGPTL8; consequently, the mice fail to replenish triglyceride stores in adipose tissue. Despite major alterations in triglyceride metabolism, no defects in glucose metabolism were detected in Angptl8 −/− mice. The finding that plasma triglyceride levels are lower in Angptl8 +/− mice suggests that even partial inhibition of ANGPTL8 may provide therapeutic benefit for treatment of dyslipidemia.