Is there a link between proprotein convertase PC7 activity and human lipid homeostasis?

• A R504H mutation in human proprotein convertase PC7 is associated with increased HDL and reduced triglycerides.
• Wild-type PC7 and its R504H mutant have identical cellular enzymatic activities.
• In situ hybridization revealed co-localization of mouse ApoF and PC7 mRNAs in liver.
• WT and PC7 KO mice do not exhibit changes in circulating levels of insulin or glucose.
• WT and PC7 KO mice do not exhibit changes in circulating levels of HDL, TG and LDL.

A genome-wide association study suggested that a R504H mutation in the proprotein convertase PC7 is associated with increased circulating levels of HDL and reduced triglycerides in black Africans. Our present results show that PC7 and PC7-R504H exhibit similar processing of transferrin receptor-1, proSortilin, and apolipoprotein-F. Plasma analyses revealed no change in the lipid profiles, insulin or glucose of wild type and PC7 KO mice. Thus, the R504H mutation does not modify the proteolytic activity of PC7. The mechanisms behind the implication of PC7 in the regulation of human HDL, triglycerides and in modifying the levels of atherogenic small dense LDL remain to be elucidated.