Overexpression of apoC-III produces lesser hypertriglyceridemia in apoB-48-only gene-targeted mice than in apoB-100-only mice.
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.
Conde-Knape
Karin
K
Department of Medicine, Columbia University, New York, NY 10032, USA.
Okada
Kenta
K
Ramakrishnan
Rajasekhar
R
Shachter
Neil S
NS
D000818:Animals; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D053305:Apolipoprotein C-III; D001055:Apolipoproteins B / Q000235:genetics* / Q000378:metabolism; D001056:Apolipoproteins C / Q000096:biosynthesis / Q000235:genetics*; D015243:Cholesterol, VLDL / Q000097:blood; D005260:Female; D018390:Gene Targeting; D015228:Hypertriglyceridemia / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D014280:Triglycerides / Q000097:blood
D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D053305:Apolipoprotein C-III; D001055:Apolipoproteins B; D001056:Apolipoproteins C; D015243:Cholesterol, VLDL; D014280:Triglycerides