Increased production of very-low-density lipoproteins in transgenic mice overexpressing human apolipoprotein A-II and fed with a high-fat diet
| Autor: | Josep Julve, Àfrica Marzal-Casacuberta, Francisco Blanco-Vaca, Joan Carles Escolà-Gil, Jordi Ordóñez-Llanos, Francesc González-Sastre |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Very low-density lipoprotein Time Factors Lipolysis Hyperlipidemia Familial Combined Mice Transgenic White adipose tissue Biology Fatty Acids Nonesterified Lipoproteins VLDL Cholesterol Dietary chemistry.chemical_compound Mice High-density lipoprotein Internal medicine medicine Animals Humans Insulin Molecular Biology Triglycerides Lipoprotein lipase Triglyceride Cholesterol Cell Biology Glucose Tolerance Test Dietary Fats Endocrinology chemistry Gene Expression Regulation Liver lipids (amino acids peptides and proteins) Female Hepatic lipase Insulin Resistance Food Deprivation Apolipoprotein A-II |
| Zdroj: | Biochimica et biophysica acta. 1488(3) |
| ISSN: | 0006-3002 |
| Popis: | 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 cholesterol and, especially, in triglyceride liver content, suggesting an enhanced mobilization of fat as the source 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 human apoA-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 major pathophysiological interest since it is the basic mechanism underlying familial combined hyperlipidemia. |
| Databáze: | OpenAIRE |
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