Hepatic lipase deficiency decreases the selective uptake of HDL-cholesteryl esters in vivo

Recent in vitro studies have provided evidence that hepatic lipase (HL) fac ilitates the selective uptake of HDL cholesteryl esters (CE), but the in vi vo physiological relevance of this process has not been demonstrated, To ev aluate the role that HL plays in facilitating the selective uptake of HDL-C E in vivo, we studied the metabolism of [H-3]CEt, I-125-labeled apolipoprot ein (apo) A-I, and I-131- labeled apoA-II-labeled HDL in HL-deficient mice. Kinetic analysis revealed similar catabolism of I-125-labeled apoA-I (as w ell as I-131-labeled apoA-II) in C57BL controls and HL deficient mice, with fractional catabolic rates (FCR) of 2.17 +/- 0.15 and 2.16 +/- 0.11 d(-1) (2.59 +/- 0.14 and 2.67 +/- 0.13 d(-1), respectively). In contrast, despite similar hepatic scavenger receptor BI expression, HL-deficient mice had de layed clearance of [H-3]CEt compared to controls (FCR = 3.66 +/- 0.29 and 4 .41 +/- 0.18 d(-1), P < 0,05), The hepatic accumulation of [H-3]CEt in HL-d eficient mice (62.3 +/- 2.1% of total) was significantly less than in contr ols (72.7 +/- 3.0%), while the [H-3]CEt remaining in the plasma compartment increased (20.7 +/- 1.8% and 12.6 +/- 0.5%) (P < 0,05, all). In summary, H L deficiency does not alter the catabolism of apoA-I and apoA-II but decrea ses the hepatic uptake and the plasma clearance of HDL-CE, These data estab lish for the first time an important role for HL in facilitating the select ive uptake of HDL-CE in vivo.Hepatic lipase deficiency decreases the select ive uptake of HDL- cholesteryl esters in vivo.