Plasma carboxyl ester lipase activity modulates apolipoprotein B-containing lipoprotein metabolism in a transgenic mouse model

Ling Li, Wei Weng, Earl H. Harrison, Edward A. Fisher

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Pancreatic carboxyl ester lipase (CEL) is in the plasma of many mammals, including humans and rats, but not mice. In vitro, CEL hydrolyzes cholesterol esters of apolipoprotein B-containing lipoproteins (apo B-Lp). To study the effect of CEL on metabolism of apo B-Lp and atherosclerosis in vivo, apo E-knockout (EKO) mice, which have high plasma levels of apo B-Lp and are prone to atherosclerosis, were made to secrete CEL into plasma by introducing a transgene containing a liver-specific promoter and rat CEL complementary DNA. Plasma CEL activity in EKO-CEL mice was comparable with that found in rats. Evidence of modification of apo B-Lp by plasma CEL in vivo was an increase in the free cholesterol to cholesterol ester ratio of apo B-Lp from mice on chow or a Western-type diet. In addition, plasma total cholesterol levels were elevated in EKO-CEL mice, with the elevation found exclusively in the apo B-Lp fraction. Associated with the increase in steady-state apo B-Lp levels was an increase in the plasma half-life of very low-density lipoproteins (VLDL) in EKO-CEL mice, measured by the clearance rate of injected VLDL. Interestingly, despite the increase of apo B-Lp, the atherosclerotic lesion did not differ between EKO and EKO-CEL mice on a Western-type diet. In summary, our results demonstrate that plasma CEL modulates apo B-Lp metabolism in vivo, resulting in reduced VLDL clearance and elevated plasma cholesterol levels.

Original languageEnglish (US)
Pages (from-to)1361-1368
Number of pages8
JournalMetabolism: clinical and experimental
Volume57
Issue number10
DOIs
StatePublished - Oct 1 2008

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