What question did this study set out to answer?

To elucidate the primary mechanism by which increased human apolipoprotein C-I expression induces combined hyperlipidemia with severe hypertriglyceridemia.

December 2, 2004Journal of Lipid ResearchOpen Access

Severe hypertriglyceridemia in human APOC1 transgenic mice is caused by apoC-I-induced inhibition of LPL

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Population

Human apoC-I-expressing mice, APOC1 mice cross-bred on an apoE-deficient background, and lactoferrin-treated…

Comparison

Increased expression of human apolipoprotein C-I… vs Control mice

Design

Preclinical

Authors

JBJimmy F.P. BerbéeLeiden University Medical Center CHCaroline C. van der HoogtUniversity Medical Center Groningen DSDeepa SundararamanNetherlands Organisation for Applied Scientific Research

Discussion

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Implication

ApoC-I may promote hypertriglyceridemia via LPL inhibition; extends mechanistic insights in transgenic mice but leaves open human relevance.

Key Points

To elucidate the primary mechanism by which increased human apolipoprotein C-I expression induces combined hyperlipidemia with severe hypertriglyceridemia.
Assessed plasma triglyceride and cholesterol profiles in human APOC1-expressing transgenic mice, control mice, and APOC1 mice cross-bred onto an apoE-deficient background.
Measured the plasma clearance kinetics and half-life of radiolabeled [3H]TG-VLDL-mimicking particles in vivo, including in lactoferrin-treated mice to block apoE-mediated uptake.
Quantified postheparin plasma LPL activity and tested in vitro dose-dependent inhibition of LPL-mediated lipolysis by purified apoC-I relative to apoC-III.
Human APOC1 mice displayed a 12-fold increase in plasma triglycerides and a 2-fold increase in total cholesterol in VLDL, expanding to a 55-fold triglyceride increase on an apoE-deficient background.
Plasma half-life of [3H]TG-VLDL-mimicking particles increased 2-fold in APOC1 mice, and purified apoC-I inhibited LPL-mediated lipolysis in vitro in a dose-dependent manner with 60% of the efficiency of apoC-III.
Purified apoC-I impaired VLDL-mimicking particle clearance in vivo independently of apoE-mediated hepatic receptor uptake in lactoferrin-treated mice.

Structured PICO

Population

Human apoC-I-expressing (APOC1) mice, APOC1 mice cross-bred on an apoE-deficient background, and lactoferrin-treated mice

Intervention

Increased expression of human apolipoprotein C-I (apoC-I) or administration of purified apoC-I

Comparator

Control mice

Outcome

Triglyceride and total cholesterol levels, and LPL-mediated lipolysis activitysurrogate

ApoC-I is a potent inhibitor of LPL-mediated TG-lipolysis, providing a mechanistic explanation for the severe hypertriglyceridemia observed with its increased expression.

Cite This Study

Berbée et al. (2004) studied this question.

synapsesocial.com/papers/6a70e368e71d69abee08ec20 https://doi.org/10.1194/jlr.m400301-jlr200

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Implication

ApoC-I may promote hypertriglyceridemia via LPL inhibition; extends mechanistic insights in transgenic mice but leaves open human relevance.

Severe hypertriglyceridemia in human APOC1 transgenic mice is caused by apoC-I-induced inhibition of LPL

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Severe hypertriglyceridemia in human APOC1 transgenic mice is caused by apoC-I-induced inhibition of LPL

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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