biostudies-literatureLarsson MAmerican Heart AssociationFondation LeducqFoundation for the National Institutes of HealthNHLBI NIH HHS1893-1902https://www.ebi.ac.uk/biostudies/studies/S-EPMC5580902biostudies-literatureUnknown58(9)apoC-III is often assumed to retard the intravascular processing of triglyceride-rich lipoproteins (TRLs) by inhibiting LPL, but that view is based largely on studies of free LPL. We now recognize that intravascular LPL is neither free nor loosely bound, but instead is tightly bound to glycosylphosphatidylinositol-anchored HDL-binding protein 1 (GPIHBP1) on endothelial cells. Here, we revisited the effects of apoC-III on LPL, focusing on apoC-III's capacity to affect the activity of GPIHBP1-bound LPL. We found that TRLs from <i>APOC3</i> transgenic mice bound normally to GPIHBP1-bound LPL on cultured cells in vitro and to heart capillaries in vivo. However, the triglycerides in apoC-III-enriched TRLs were hydrolyzed more slowly by free LPL, and the inhibitory effect of apoC-III on triglyceJournal of lipid researchApolipoprotein C-III inhibits triglyceride hydrolysis by GPIHBP1-bound LPL.PMC558090215POST22960055P01 HL09055312CVD04Fong LGLarsson MHeizer PJJung RSYoung SGBeigneux APAllan CMfalseApolipoprotein C-III inhibits triglyceride hydrolysis by GPIHBP1-bound LPL.apoC-III is often assumed to retard the intravascular processing of triglyceride-rich lipoproteins (TRLs) by inhibiting LPL, but that view is based largely on studies of free LPL. We now recognize that intravascular LPL is neither free nor loosely bound, but instead is tightly bound to glycosylphosphatidylinositol-anchored HDL-binding protein 1 (GPIHBP1) on endothelial cells. Here, we revisited the effects of apoC-III on LPL, focusing on apoC-III's capacity to affect the activity of GPIHBP1-bound LPL. We found that TRLs from <i>APOC3</i> transgenic mice bound normally to GPIHBP1-bound LPL on cultured cells in vitro and to heart capillaries in vivo. However, the triglycerides in apoC-III-enriched TRLs were hydrolyzed more slowly by free LPL, and the inhibitory effect of apoC-III on triglyce2017-01-01T00:00:00Z2017 Sep2025-04-19T22:15:53.133Z2019-03-26T23:53:08ZS-EPMC55809022869429610.1194/jlr.M07822010.1194/jlr.m078220