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Titolo:
Increased production of very-low-density lipoproteins in transgenic mice overexpressing human apolipoprotein A-II and fed with a high-fat diet
Autore:
Julve, J; Escola-Gil, JC; Marzal-Casacuberta, A; Ordonez-Llanos, J; Gonzalez-Sastre, F; Blanco-Vaca, F;
Indirizzi:
Hosp Santa Cruz & San Pablo, Serv Bioquim, E-08025 Barcelona, Spain Hosp Santa Cruz & San Pablo Barcelona Spain E-08025 025 Barcelona, Spain Hosp Santa Cruz & San Pablo, Inst Rec, E-08025 Barcelona, Spain Hosp SantaCruz & San Pablo Barcelona Spain E-08025 025 Barcelona, Spain Univ Autonoma Barcelona, Dept Bioquim & Biol Mol, E-08193 Barcelona, SpainUniv Autonoma Barcelona Barcelona Spain E-08193 E-08193 Barcelona, Spain
Titolo Testata:
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
fascicolo: 3, volume: 1488, anno: 2000,
pagine: 233 - 244
SICI:
1388-1981(20001115)1488:3<233:IPOVLI>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
CHOLESTEROL ACYLTRANSFERASE DEFICIENCY; FUNCTIONAL LECITHIN; LIPASE ACTIVITIES; ADIPOSE-TISSUE; LCAT GENE; ACID; HYPERTRIGLYCERIDEMIA; METABOLISM; PROTEIN; TRIGLYCERIDE;
Keywords:
apolipoprotein A-II; atherosclerosis; high density lipoprotein; familial combined hyperlipidemia; VLDL metabolism;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Blanco-Vaca, F Hosp Santa Cruz & San Pablo, Serv Bioquim, Antoni M Claret 167, E-08025 Barcelona, Spain Hosp Santa Cruz & San Pablo Antoni M Claret 167 Barcelona Spain E-08025
Citazione:
J. Julve et al., "Increased production of very-low-density lipoproteins in transgenic mice overexpressing human apolipoprotein A-II and fed with a high-fat diet", BBA-MOL C B, 1488(3), 2000, pp. 233-244

Abstract

We investigated the mechanisms that lead to combined hyperlipidemia in transgenic mice that overexpress human apolipoprotein (apo) A-II (line 11.1). The 11.1 transgenic mice develop pronounced hypertriglyceridemia, and a moderate increase in free fatty acid (FFA) and plasma cholesterol, especially when fed a high-fat/high-cholesterol diet. Post-heparin plasma lipoprotein lipase and hepatic lipase activities (using artificial or natural autologous substrates), the decay of plasma triglycerides with fasting, and the fractional catabolic rate of the radiolabeled VLDL-triglyceride (both fasting and postprandial) were similar in 11.1 transgenic mice and in control mice. In contrast, a 2.5-fold increase in hepatic VLDL-triglyceride production was observed in 11.1 transgenic mice in a period of 2 h in which blood lipolysis was inhibited. This increased synthesis of hepatic VLDL-triglyceride used preformed FFA rather than FFA of de novo hepatic synthesis. The 11.1 transgenic mice also presented reduced epididymal/parametrial white adipose tissue weight (1.5-fold), increased rate of epididymal/parametrial hormone-sensitive lipase-mediated lipolysis (1.2-fold) and an increase in cholesteroland, especially, in triglyceride liver content, suggesting an enhanced mobilization of fat as the sourer of preformed FFA reaching the liver. Increased plasma FFA was reverted by insulin, demonstrating that 11.1 transgenic mice are not insulin resistant. We conclude that the overexpression of humanapoA-II in transgenic mice induces combined hyperlipidemia through an increase in VLDL production. These mice will be useful in the study of molecular mechanisms that regulate the overproduction of VLDL, a situation of majorpathophysiological interest since it is the basic mechanism underlying familial combined hyperlipidemia. (C) 2000 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/04/20 alle ore 04:14:01