Versatile Functions of Hepatic Lipase in Lipoprotein Metabolism

Despite a growing therapeutic arsenal, atherosclerotic cardiovascular disease remains the major cause of mortality worldwide. Hepatic lipase, encoded by the gene LIPC (lipase C, hepatic type), is a protein that has recently regained interest in this context. In this review, we provide a comprehensive overview of the versatile roles of hepatic lipase in lipoprotein metabolism, with a focus on the recently discovered LIPC-E97G (point mutation replacing glutamic acid with glycine at position 97) variant. Specifically, we discuss the roles of hepatic lipase in the metabolism of high-density lipoproteins and apoB-containing lipoproteins, as elucidated through in vitro, in vivo, and genetic studies. We also explore the complex interplay between the antiatherogenic and proatherogenic effects of hepatic lipase, highlighting a predominance of antiatherogenic functions for hepatic lipase. Lastly, we briefly discuss how the knowledge on the function of hepatic lipase can potentially be harnessed for the treatment of atherosclerotic cardiovascular disease.