Abstract | 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. METHODS AND 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:
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Authors | Rien van Haperen, Hannelore Samyn, Teus van Gent, Adri J Zonneveld, Matthijs Moerland, Frank Grosveld, Hans Jansen, Geesje M Dallinga-Thie, Arie van Tol, Rini de Crom |
Journal | Biochimica et biophysica acta
(Biochim Biophys Acta)
Vol. 1791
Issue 10
Pg. 1031-6
(Oct 2009)
ISSN: 0006-3002 [Print] Netherlands |
PMID | 19524061
(Publication Type: Journal Article)
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Chemical References |
- Cholesterol, HDL
- Cholesterol, VLDL
- Membrane Proteins
- Phospholipid Transfer Proteins
- Lipase
- Lipc protein, mouse
- Lipoprotein Lipase
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Topics |
- Animals
- Cholesterol, HDL
(blood, metabolism)
- Cholesterol, VLDL
(blood, metabolism)
- Lipase
(blood, metabolism)
- Lipoprotein Lipase
(blood)
- Membrane Proteins
(metabolism)
- Mice
- Mice, Transgenic
- Phospholipid Transfer Proteins
(blood, metabolism)
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