Submitted on May 14, 2004
Revised on August 10, 2004
Accepted on August 29, 2004
Overexpression of apoC-III produces lesser hypertriglyceridemia in apoB48-only gene-targeted mice than in apoB100-only mice
Karin Conde-Knape, Kenta Okada, Rajasekhar Ramakrishnan, and Neil S. Shachter
Department of Medicine, Columbia University, New York, NY 10032
Corresponding Author: nss5{at}columbia.edu
The adaptive value of apoB48, 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 apoB48 only (apo-B48/48) or apoB100 only (apo-B100/100). Cholesterol levels were higher in apo-B48/48 mice than in apo-B100/100 mice but triglyceride levels were similar. Lipid levels were increased by the apoC-III transgene. However, triglyceride levels (mg/dl) were significantly higher in apo-B100/100C-III than in apo-B48/48C-III mice (895±395 vs. 690±252, P <0.01), while cholesterol levels were higher in the apo-B48/48C-III mice (144±35 vs. 94±30 in apo-B100/100C-III, P <0.00001). Triglyceride clearance from VLDL was impaired to a greater extent in apo-B100/100C-III vs. apo-B100/100 mice than in apo-B48/48C-III vs. apo-B48/48 mice. Triglyceride secretion rates were no different in apoC-III transgenic mice than in their non-transgenic littermates. ApoB48 triglyceride-rich lipoproteins were more resistant to the triglyceride-raising effects of apoC-III but appeared more sensitive to the remnant clearance inhibition. Our findings support a coordinated role for apoB48 in facilitating the delivery of dietary triglycerides to the periphery. Consistent with such a mechanism, glucose levels were significantly higher in apo-B48/48 mice vs. apo-B100/100 mice, perhaps on the basis of metabolic competition.
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