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Originally published In Press as doi:10.1194/jlr.M400185-JLR200 on September 1, 2004

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Journal of Lipid Research, Vol. 45, 2235-2244, December 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Overexpression of apoC-III produces lesser hypertriglyceridemia in apoB-48-only gene-targeted mice than in apoB-100-only mice

Karin Conde-Knape1,*, Kenta Okada2,*, Rajasekhar Ramakrishnan{dagger} and Neil S. Shachter3,*

* Departments of Medicine, Columbia University, New York, NY 10032
{dagger} Pediatrics, Columbia University, New York, NY 10032

3 To whom correspondence should be addressed. e-mail: nss5{at}columbia.edu

The adaptive value of apolipoprotein B-48 (apoB-48), the truncated form of apoB produced by the intestine, in lipid metabolism remains unclear. We crossed human apoC-III transgenic mice with mice expressing either apoB-48 only (apoB48/48) or apoB-100 only (apoB100/100). Cholesterol levels were higher in apoB48/48 mice than in apoB100/100 mice but triglyceride levels were similar. Lipid levels were increased by the apoC-III transgene. However, triglyceride levels were significantly higher in apoB100/100C-III than in apoB48/48C-III mice (895 ± 395 mg/dl vs. 690 ± 252 mg/dl; P < 0.01), whereas cholesterol levels were higher in the apoB48/48C-III mice than in apoB100/100C-III (144 ± 35 mg/dl vs. 94 ± 30 mg/dl; P < 0.00001). Triglyceride clearance from VLDL was impaired to a greater extent in apoB100/100C-III vs. apoB100/100 mice than in apoB48/48C-III vs. apoB48/48 mice. Triglyceride secretion rates were no different in apoC-III transgenic mice than in their nontransgenic littermates. ApoB-48 triglyceride-rich lipoproteins were more resistant to the triglyceride-increasing effects of apoC-III but appeared more sensitive to the remnant clearance inhibition.

Our findings support a coordinated role for apoB-48 in facilitating the delivery of dietary triglycerides to the periphery. Consistent with such a mechanism, glucose levels were significantly higher in apoB48/48 mice vs. apoB100/100 mice, perhaps on the basis of metabolic competition.

Supplementary key words apolipoproteins C • apolipoproteins B • hyperglycemia • transgenic • postprandial period


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