Endogenous apoC-I increases hyperlipidemia in apoE-knockout mice by stimulating VLDL production and inhibiting LPL
Previous studies have shown that overexpression of human apolipoprotein C-I (apoC-I) results in moderate hypercholesterolemia and severe hypertriglyceridemia in mice in the presence and absence of apoE. We assessed whether physiological endogenous apoC-I levels are sufficient to modulate plasma lipi...
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doaj-8f3483df38d74b95b5ab78a247d884362021-04-27T04:44:31ZengElsevierJournal of Lipid Research0022-22752006-06-0147612031211Endogenous apoC-I increases hyperlipidemia in apoE-knockout mice by stimulating VLDL production and inhibiting LPLMarit Westerterp0Willeke de Haan1Jimmy F.P. Berbeée2Louis M. Havekes3Patrick C.N. Rensen4Netherlands Organization for Applied Scientific Research-Quality of Life, Department of Biomedical Research, Gaubius Laboratory, 2301 CE Leiden, The Netherlands; Departments of General Internal Medicine, Endocrinology, and Metabolism, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsNetherlands Organization for Applied Scientific Research-Quality of Life, Department of Biomedical Research, Gaubius Laboratory, 2301 CE Leiden, The Netherlands; Departments of General Internal Medicine, Endocrinology, and Metabolism, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsNetherlands Organization for Applied Scientific Research-Quality of Life, Department of Biomedical Research, Gaubius Laboratory, 2301 CE Leiden, The Netherlands; Departments of General Internal Medicine, Endocrinology, and Metabolism, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsNetherlands Organization for Applied Scientific Research-Quality of Life, Department of Biomedical Research, Gaubius Laboratory, 2301 CE Leiden, The Netherlands; Departments of General Internal Medicine, Endocrinology, and Metabolism, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; Department of Cardiology, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsNetherlands Organization for Applied Scientific Research-Quality of Life, Department of Biomedical Research, Gaubius Laboratory, 2301 CE Leiden, The Netherlands; Departments of General Internal Medicine, Endocrinology, and Metabolism, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsPrevious studies have shown that overexpression of human apolipoprotein C-I (apoC-I) results in moderate hypercholesterolemia and severe hypertriglyceridemia in mice in the presence and absence of apoE. We assessed whether physiological endogenous apoC-I levels are sufficient to modulate plasma lipid levels independently of effects of apoE on lipid metabolism by comparing apolipoprotein E gene-deficient/apolipoprotein C-I gene-deficient (apoe−/−apoc1−/−), apoe−/−apoc1+/−, and apoe−/−apoc1+/+ mice. The presence of the apoC-I gene-dose-dependently increased plasma cholesterol (+45%; P < 0.001) and triglycerides (TGs) (+137%; P < 0.001), both specific for VLDL. Whereas apoC-I did not affect intestinal [3H]TG absorption, it increased the production rate of hepatic VLDL-TG (+35%; P < 0.05) and VLDL-[35S]apoB (+39%; P < 0.01). In addition, apoC-I increased the postprandial TG response to an intragastric olive oil load (+120%; P < 0.05) and decreased the uptake of [3H]TG-derived FFAs from intravenously administered VLDL-like emulsion particles by gonadal and perirenal white adipose tissue (WAT) (−34% and −25%, respectively; P < 0.05). As LPL is the main enzyme involved in the clearance of TG-derived FFAs by WAT, and total postheparin plasma LPL levels were unaffected, these data demonstrate that endogenous apoC-I suffices to attenuate the lipolytic activity of LPL. Thus, we conclude that endogenous plasma apoC-I increases VLDL-total cholesterol and VLDL-TG dose-dependently in apoe−/− mice, resulting from increased VLDL particle production and LPL inhibition.http://www.sciencedirect.com/science/article/pii/S0022227520332193apolipoprotein C-Iapolipoprotein Elipasestransgenic mouse modelslipoprotein lipasevery low density lipoprotein |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marit Westerterp Willeke de Haan Jimmy F.P. Berbeée Louis M. Havekes Patrick C.N. Rensen |
spellingShingle |
Marit Westerterp Willeke de Haan Jimmy F.P. Berbeée Louis M. Havekes Patrick C.N. Rensen Endogenous apoC-I increases hyperlipidemia in apoE-knockout mice by stimulating VLDL production and inhibiting LPL Journal of Lipid Research apolipoprotein C-I apolipoprotein E lipases transgenic mouse models lipoprotein lipase very low density lipoprotein |
author_facet |
Marit Westerterp Willeke de Haan Jimmy F.P. Berbeée Louis M. Havekes Patrick C.N. Rensen |
author_sort |
Marit Westerterp |
title |
Endogenous apoC-I increases hyperlipidemia in apoE-knockout mice by stimulating VLDL production and inhibiting LPL |
title_short |
Endogenous apoC-I increases hyperlipidemia in apoE-knockout mice by stimulating VLDL production and inhibiting LPL |
title_full |
Endogenous apoC-I increases hyperlipidemia in apoE-knockout mice by stimulating VLDL production and inhibiting LPL |
title_fullStr |
Endogenous apoC-I increases hyperlipidemia in apoE-knockout mice by stimulating VLDL production and inhibiting LPL |
title_full_unstemmed |
Endogenous apoC-I increases hyperlipidemia in apoE-knockout mice by stimulating VLDL production and inhibiting LPL |
title_sort |
endogenous apoc-i increases hyperlipidemia in apoe-knockout mice by stimulating vldl production and inhibiting lpl |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2006-06-01 |
description |
Previous studies have shown that overexpression of human apolipoprotein C-I (apoC-I) results in moderate hypercholesterolemia and severe hypertriglyceridemia in mice in the presence and absence of apoE. We assessed whether physiological endogenous apoC-I levels are sufficient to modulate plasma lipid levels independently of effects of apoE on lipid metabolism by comparing apolipoprotein E gene-deficient/apolipoprotein C-I gene-deficient (apoe−/−apoc1−/−), apoe−/−apoc1+/−, and apoe−/−apoc1+/+ mice. The presence of the apoC-I gene-dose-dependently increased plasma cholesterol (+45%; P < 0.001) and triglycerides (TGs) (+137%; P < 0.001), both specific for VLDL. Whereas apoC-I did not affect intestinal [3H]TG absorption, it increased the production rate of hepatic VLDL-TG (+35%; P < 0.05) and VLDL-[35S]apoB (+39%; P < 0.01). In addition, apoC-I increased the postprandial TG response to an intragastric olive oil load (+120%; P < 0.05) and decreased the uptake of [3H]TG-derived FFAs from intravenously administered VLDL-like emulsion particles by gonadal and perirenal white adipose tissue (WAT) (−34% and −25%, respectively; P < 0.05). As LPL is the main enzyme involved in the clearance of TG-derived FFAs by WAT, and total postheparin plasma LPL levels were unaffected, these data demonstrate that endogenous apoC-I suffices to attenuate the lipolytic activity of LPL. Thus, we conclude that endogenous plasma apoC-I increases VLDL-total cholesterol and VLDL-TG dose-dependently in apoe−/− mice, resulting from increased VLDL particle production and LPL inhibition. |
topic |
apolipoprotein C-I apolipoprotein E lipases transgenic mouse models lipoprotein lipase very low density lipoprotein |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520332193 |
work_keys_str_mv |
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