Novel roles of hepatic lipase and phospholipid transfer protein in VLDL as well as HDL metabolism.
OBJECTIVE
Elevated plasma phospholipid transfer protein (PLTP) expression may increase atherosclerosis in mice by reducing plasma HDL and increasing hepatic VLDL secretion. Hepatic lipase (HL) is a lipolytic enzyme involved in several aspects of the same pathways of lipoprotein metabolism. We investigated whether the effects of elevated PLTP activity are compromised by HL deficiency.


RESULTS
HL deficient mice were crossbred with PLTP transgenic (PLTPtg) mice and studied in the fasted state. Plasma triglycerides were decreased in HL deficiency, explained by reduced hepatic triglyceride secretion. In PLTPtg mice, a redistribution of HL activity between plasma and tissue was evident and plasma triglycerides were also decreased. HL deficiency mitigated or even abolished the stimulatory effect of elevated PLTP activity on hepatic triglyceride secretion. HL deficiency had a modest incremental effect on plasma HDL, which remained present in PLTP transgenic/HL(-/-) mice, thereby partially compensating the decrease in HDL caused by elevation of PLTP activity. HDL decay experiments showed that the fractional turnover rate of HDL cholesteryl esters was delayed in HL deficient mice, increased in PLTPtg mice and intermediate in PLTPtg mice in an HL(-/-) background.


CONCLUSIONS
HL affects hepatic VLDL. Elevated PLTP activity lowers plasma HDL-cholesterol by stimulating the plasma turnover and hepatic uptake of HDL cholesteryl esters. HL is not required for the increase in hepatic triglyceride secretion or for the lowering of HDL-cholesterol induced by PLTP overexpression.
van Haperen
Rien
R
Department of Cell Biology and Genetics, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
Samyn
Hannelore
H
van Gent
Teus
T
Zonneveld
Adri J
AJ
Moerland
Matthijs
M
Grosveld
Frank
F
Jansen
Hans
H
Dallinga-Thie
Geesje M
GM
van Tol
Arie
A
de Crom
Rini
R
D000818:Animals; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism*; D015243:Cholesterol, VLDL / Q000097:blood / Q000378:metabolism*; D008049:Lipase / Q000097:blood / Q000378:metabolism*; D008071:Lipoprotein Lipase / Q000097:blood; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D049294:Phospholipid Transfer Proteins / Q000097:blood / Q000378:metabolism*
D008076:Cholesterol, HDL; D015243:Cholesterol, VLDL; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D008049:Lipase; C495700:Lipc protein, mouse; D008071:Lipoprotein Lipase