Overexpression ofapoC-III produces lesser hypertriglyceridemia in apoB-48-only gene-targeted micethan in apoB-100-only mice

Abstract

The adaptive value of apolipoprotein B-48 (apoB-48), thetruncated form of apoB produced by the intestine, in lipid metabolism remainsunclear. We crossed human apoC-III transgenic mice with mice expressing eitherapoB-48 only (apoB48/48) or apoB-100 only(apoB100/100). Cholesterol levels were higher inapoB48/48 mice than in apoB100/100 micebut triglyceride levels were similar. Lipid levels were increased by the apoC-IIItransgene. However, triglyceride levels were significantly higher inapoB100/100C-III than in apoB48/48C-IIImice (895 ± 395 mg/dl vs. 690 ± 252 mg/dl; P <0.01), whereas cholesterol levels were higher in theapoB48/48C-III mice than inapoB100/100C-III (144 ± 35 mg/dl vs. 94 ± 30mg/dl; P < 0.00001). Triglyceride clearance from VLDL wasimpaired to a greater extent in apoB100/100C-III vs.apoB100/100 mice than in apoB48/48C-IIIvs. apoB48/48 mice. Triglyceride secretion rates were nodifferent in apoC-III transgenic mice than in their nontransgenic littermates.ApoB-48 triglyceride-rich lipoproteins were more resistant to thetriglyceride-increasing effects of apoC-III but appeared more sensitive to theremnant clearance inhibition.Our findings support a coordinated role forapoB-48 in facilitating the delivery of dietary triglycerides to the periphery.Consistent with such a mechanism, glucose levels were significantly higher inapoB48/48 mice vs. apoB100/100 mice,perhaps on the basis of metabolic competition.

Keywords

• apolipoproteins C
• apolipoproteinsB
• hyperglycemia
• transgenic
• postprandialperiod