Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 30 November 1990:
Vol. 250. no. 4985, pp. 1273 - 1275
DOI: 10.1126/science.2244210
Prev | Table of Contents | Next

Articles

Science, Vol 250, Issue 4985, 1273-1275
Copyright © 1990 by American Association for the Advancement of Science

articles

Diet-induced hypercholesterolemia in mice: prevention by overexpression of LDL receptors

M Yokode, RE Hammer, S Ishibashi, MS Brown, and JL Goldstein

Department of Molecular Genetics, University of Texas, Southwestern Medical Center, Dallas 75235.

The current studies were designed to determine whether chronic overexpression of low density lipoprotein (LDL) receptors in the liver would protect mice from the increase in plasma LDL-cholesterol that is induced by high-fat diets. A line of transgenic mice was studied that express the human LDL receptor gene in the liver under control of the transferrin promoter. When fed a diet containing cholesterol, saturated fat, and bile acids for 3 weeks, the transgenic mice, in contrast to normal mice, did not develop a detectable increase in plasma LDL. The current data indicate that unregulated overexpression of LDL receptors can protect against diet-induced hypercholesterolemia in mice.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Noninvasive Quantification of Pancreatic Fat in Humans.
I. Lingvay, V. Esser, J. L. Legendre, A. L. Price, K. M. Wertz, B. Adams-Huet, S. Zhang, R. H. Unger, and L. S. Szczepaniak (2009)
J. Clin. Endocrinol. Metab. 94, 4070-4076
   Abstract »    Full Text »    PDF »
Developmental programming of sex-dependent alterations in lipid metabolism: a role for long-term, sex-specific alterations in LDL-receptor expression. Focus on "Developmental programming of lipid metabolism and aortic vascular function in C57BL/6 mice: a novel study suggesting an involvement of LDL-receptor".
B. T. Alexander (2009)
Am J Physiol Regulatory Integrative Comp Physiol 296, R1027-R1028
   Full Text »    PDF »
Fibroblast Growth Factor 21 Reverses Hepatic Steatosis, Increases Energy Expenditure, and Improves Insulin Sensitivity in Diet-Induced Obese Mice.
J. Xu, D. J. Lloyd, C. Hale, S. Stanislaus, M. Chen, G. Sivits, S. Vonderfecht, R. Hecht, Y.-S. Li, R. A. Lindberg, et al. (2009)
Diabetes 58, 250-259
   Abstract »    Full Text »    PDF »
Human LDL Receptor Enhances Sequestration of ApoE4 and VLDL Remnants on the Surface of Hepatocytes but Not Their Internalization in Mice.
M. Altenburg, J. Arbones-Mainar, L. Johnson, J. Wilder, and N. Maeda (2008)
Arterioscler Thromb Vasc Biol 28, 1104-1110
   Abstract »    Full Text »    PDF »
Phospholipid transfer protein deficiency ameliorates diet-induced hypercholesterolemia and inflammation in mice.
L. Shelly, L. Royer, T. Sand, H. Jensen, and Y. Luo (2008)
J. Lipid Res. 49, 773-781
   Abstract »    Full Text »    PDF »
Clock mutation facilitates accumulation of cholesterol in the liver of mice fed a cholesterol and/or cholic acid diet.
T. Kudo, M. Kawashima, T. Tamagawa, and S. Shibata (2008)
Am J Physiol Endocrinol Metab 294, E120-E130
   Abstract »    Full Text »    PDF »
Tissue- and Nuclear Receptor-Specific Function of the C-Terminal LXXLL Motif of Coactivator NCoA6/AIB3 in Mice.
Q. Li, M.-J. Chu, and J. Xu (2007)
Mol. Cell. Biol. 27, 8073-8086
   Abstract »    Full Text »    PDF »
Attenuating Effect of Clock Mutation on Triglyceride Contents in the ICR Mouse Liver under a High-Fat Diet.
T. Kudo, T. Tamagawa, M. Kawashima, N. Mito, and S. Shibata (2007)
J Biol Rhythms 22, 312-323
   Abstract »    PDF »
Inaugural Article: Analysis of HSD3B7 knockout mice reveals that a 3{alpha}-hydroxyl stereochemistry is required for bile acid function.
H. C. Shea, D. D. Head, K. D. R. Setchell, and D. W. Russell (2007)
PNAS 104, 11526-11533
   Abstract »    Full Text »    PDF »
Hepatic lipid accumulation in apolipoprotein C-I-deficient mice is potentiated by cholesteryl ester transfer protein.
T. Gautier, U. J. F. Tietge, R. Boverhof, F. G. Perton, N. Le Guern, D. Masson, P. C. N. Rensen, L. M. Havekes, L. Lagrost, and F. Kuipers (2007)
J. Lipid Res. 48, 30-40
   Abstract »    Full Text »    PDF »
Cross-talk between Thyroid Hormone Receptor and Liver X Receptor Regulatory Pathways Is Revealed in a Thyroid Hormone Resistance Mouse Model.
K. Hashimoto, R. N. Cohen, M. Yamada, K. R. Markan, T. Monden, T. Satoh, M. Mori, and F. E. Wondisford (2006)
J. Biol. Chem. 281, 295-302
   Abstract »    Full Text »    PDF »
Chronic intermittent hypoxia upregulates genes of lipid biosynthesis in obese mice.
J. Li, D. N. Grigoryev, S. Q. Ye, L. Thorne, A. R. Schwartz, P. L. Smith, C. P. O'Donnell, and V. Y. Polotsky (2005)
J Appl Physiol 99, 1643-1648
   Abstract »    Full Text »    PDF »
Lack of stimulation of cholesteryl ester transfer protein by cholesterol in the presence of a high-fat diet.
S. K. Cheema, A. Agarwal-Mawal, C. M. Murray, and S. Tucker (2005)
J. Lipid Res. 46, 2356-2366
   Abstract »    Full Text »    PDF »
Bovine Growth Hormone Transgenic Mice Are Resistant to Diet-Induced Obesity but Develop Hyperphagia, Dyslipidemia, and Diabetes on a High-Fat Diet.
B. Olsson, M. Bohlooly-Y, S. M. Fitzgerald, F. Frick, A. Ljungberg, B. Ahren, J. Tornell, G. Bergstrom, and J. Oscarsson (2005)
Endocrinology 146, 920-930
   Abstract »    Full Text »    PDF »
Post-transcriptional Regulation of Low Density Lipoprotein Receptor Protein by Proprotein Convertase Subtilisin/Kexin Type 9a in Mouse Liver.
S. W. Park, Y.-A. Moon, and J. D. Horton (2004)
J. Biol. Chem. 279, 50630-50638
   Abstract »    Full Text »    PDF »
Apolipoprotein E Modulates Clearance of Apoptotic Bodies In Vitro and In Vivo, Resulting in a Systemic Proinflammatory State in Apolipoprotein E-Deficient Mice.
D. J. Grainger, J. Reckless, and E. McKilligin (2004)
J. Immunol. 173, 6366-6375
   Abstract »    Full Text »    PDF »
p53 Involvement in the Pathogenesis of Fatty Liver Disease.
N. Yahagi, H. Shimano, T. Matsuzaka, M. Sekiya, Y. Najima, S. Okazaki, H. Okazaki, Y. Tamura, Y. Iizuka, N. Inoue, et al. (2004)
J. Biol. Chem. 279, 20571-20575
   Abstract »    Full Text »    PDF »
From The Cover: Deficiency of carbohydrate response element-binding protein (ChREBP) reduces lipogenesis as well as glycolysis.
K. Iizuka, R. K. Bruick, G. Liang, J. D. Horton, and K. Uyeda (2004)
PNAS 101, 7281-7286
   Abstract »    Full Text »    PDF »
Early Embryonic Lethality Caused by Targeted Disruption of the 3-Hydroxy-3-methylglutaryl-CoA Reductase Gene.
K. Ohashi, J.-i. Osuga, R. Tozawa, T. Kitamine, H. Yagyu, M. Sekiya, S. Tomita, H. Okazaki, Y. Tamura, N. Yahagi, et al. (2003)
J. Biol. Chem. 278, 42936-42941
   Abstract »    Full Text »    PDF »
Normal Sorting but Defective Endocytosis of the Low Density Lipoprotein Receptor in Mice with Autosomal Recessive Hypercholesterolemia.
C. Jones, R. E. Hammer, W.-P. Li, J. C. Cohen, H. H. Hobbs, and J. Herz (2003)
J. Biol. Chem. 278, 29024-29030
   Abstract »    Full Text »    PDF »
Activating Signal Cointegrator 2 Required for Liver Lipid Metabolism Mediated by Liver X Receptors in Mice.
S.-W. Kim, K. Park, E. Kwak, E. Choi, S. Lee, J. Ham, H. Kang, J. M. Kim, S. Y. Hwang, Y.-Y. Kong, et al. (2003)
Mol. Cell. Biol. 23, 3583-3592
   Abstract »    Full Text »    PDF »
Quantitative trait loci that determine lipoprotein cholesterol levels in DBA/2J and CAST/Ei inbred mice,.
M. A. Lyons, H. Wittenburg, R. Li, K. A. Walsh, G. A. Churchill, M. C. Carey, and B. Paigen (2003)
J. Lipid Res. 44, 953-967
   Abstract »    Full Text »    PDF »
A Natural Product That Lowers Cholesterol As an Antagonist Ligand for FXR.
N. L. Urizar, A. B. Liverman, D'N. T. Dodds, F. V. Silva, P. Ordentlich, Y. Yan, F. J. Gonzalez, R. A. Heyman, D. J. Mangelsdorf, and D. D. Moore (2002)
Science 296, 1703-1706
   Abstract »    Full Text »    PDF »
Absence of Sterol Regulatory Element-binding Protein-1 (SREBP-1) Ameliorates Fatty Livers but Not Obesity or Insulin Resistance in Lepob/Lepob Mice.
N. Yahagi, H. Shimano, A. H. Hasty, T. Matsuzaka, T. Ide, T. Yoshikawa, M. Amemiya-Kudo, S. Tomita, H. Okazaki, Y. Tamura, et al. (2002)
J. Biol. Chem. 277, 19353-19357
   Abstract »    Full Text »    PDF »
Increased Expression of the Sterol Regulatory Element-binding Protein-1 Gene in Insulin Receptor Substrate-2-/- Mouse Liver.
K. Tobe, R. Suzuki, M. Aoyama, T. Yamauchi, J. Kamon, N. Kubota, Y. Terauchi, J. Matsui, Y. Akanuma, S. Kimura, et al. (2001)
J. Biol. Chem. 276, 38337-38340
   Abstract »    Full Text »    PDF »
SREBP cleavage-activating protein (SCAP) is required for increased lipid synthesis in liver induced by cholesterol deprivation and insulin elevation.
M. Matsuda, B. S. Korn, R. E. Hammer, Y.-A. Moon, R. Komuro, J. D. Horton, J. L. Goldstein, M. S. Brown, and I. Shimomura (2001)
Genes & Dev. 15, 1206-1216
   Abstract »    Full Text »
Glucokinase Gene Locus Transgenic Mice Are Resistant to the Development of Obesity-Induced Type 2 Diabetes.
M. Shiota, C. Postic, Y. Fujimoto, T. L. Jetton, K. Dixon, D. Pan, J. Grimsby, J. F. Grippo, M. A. Magnuson, and A. D. Cherrington (2001)
Diabetes 50, 622-629
   Abstract »    Full Text »
Role of LXRs in control of lipogenesis.
J. R. Schultz, H. Tu, A. Luk, J. J. Repa, J. C. Medina, L. Li, S. Schwendner, S. Wang, M. Thoolen, D. J. Mangelsdorf, et al. (2000)
Genes & Dev. 14, 2831-2838
   Abstract »    Full Text »
A sensitive and convenient method for lipoprotein profile analysis of individual mouse plasma samples.
D. W. Garber, K. R. Kulkarni, and G. M. Anantharamaiah (2000)
J. Lipid Res. 41, 1020-1026
   Abstract »    Full Text »
Dietary fat and reduced levels of TGFbeta1 act synergistically to promote activation of the vascular endothelium and formation of lipid lesions.
D. Grainger, D. Mosedale, J. Metcalfe, and E. Bottinger (2000)
J. Cell Sci. 113, 2355-2361
   Abstract »    PDF »
Sterol Regulatory Element-binding Protein-1 as a Key Transcription Factor for Nutritional Induction of Lipogenic Enzyme Genes.
H. Shimano, N. Yahagi, M. Amemiya-Kudo, A. H. Hasty, J.-i. Osuga, Y. Tamura, F. Shionoiri, Y. Iizuka, K. Ohashi, K. Harada, et al. (1999)
J. Biol. Chem. 274, 35832-35839
   Abstract »    Full Text »    PDF »
Increased Levels of Nuclear SREBP-1c Associated with Fatty Livers in Two Mouse Models of Diabetes Mellitus.
I. Shimomura, Y. Bashmakov, and J. D. Horton (1999)
J. Biol. Chem. 274, 30028-30032
   Abstract »    Full Text »    PDF »
Metabolism of Cholesterol Is Altered in the Liver of C3H Mice Fed Fats Enriched with Different C-18 Fatty Acids.
S. K. Cheema and L. B. Agellon (1999)
J. Nutr. 129, 1718-1724
   Abstract »    Full Text »
Compensated endocytosis of LDL by hamster cells co-expressing the two distinct mutant LDL receptors defective in endocytosis and ligand binding.
H. Yoshida, M. Yokode, A. Yamamoto, R. Masaki, T. Murayama, H. Horiuchi, and T. Kita (1999)
J. Lipid Res. 40, 814-823
   Abstract »    Full Text »
Lower Plasma Levels and Accelerated Clearance of High Density Lipoprotein (HDL) and Non-HDL Cholesterol in Scavenger Receptor Class B Type I Transgenic Mice.
Y. Ueda, L. Royer, E. Gong, J. Zhang, P. N. Cooper, O. Francone, and E. M. Rubin (1999)
J. Biol. Chem. 274, 7165-7171
   Abstract »    Full Text »    PDF »
Mammary Gland Expression of Mouse Mammary Tumor Virus Is Regulated by a Novel Element in the Long Terminal Repeat.
W. Qin, T. V. Golovkina, T. Peng, I. Nepomnaschy, V. Buggiano, I. Piazzon, and S. R. Ross (1999)
J. Virol. 73, 368-376
   Abstract »    Full Text »    PDF »
Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy.
I. Shimomura, R. E. Hammer, J. A. Richardson, S. Ikemoto, Y. Bashmakov, J. L. Goldstein, and M. S. Brown (1998)
Genes & Dev. 12, 3182-3194
   Abstract »    Full Text »
Knockout of the abetalipoproteinemia gene in mice: Reduced lipoprotein secretion in heterozygotes and embryonic lethality in homozygotes.
M. Raabe, L. M. Flynn, C. H. Zlot, J. S. Wong, M. M. Veniant, R. L. Hamilton, and S. G. Young (1998)
PNAS 95, 8686-8691
   Abstract »    Full Text »    PDF »
Lipoprotein lipase mediates an increase in the selective uptake of high density lipoprotein-associated cholesteryl esters by hepatic cells in culture.
F. Rinninger, T. Kaiser, W. A. Mann, N. Meyer, H. Greten, and U. Beisiegel (1998)
J. Lipid Res. 39, 1335-1348
   Abstract »    Full Text »
An efficient chromatographic system for lipoprotein fractionation using whole plasma.
W. Innis-Whitehouse, X. Li, W. V. Brown, and N.-A. Le (1998)
J. Lipid Res. 39, 679-690
   Abstract »    Full Text »
Atherogenic Lipoproteins Support Assembly of the Prothrombinase Complex and Thrombin Generation: Modulation by Oxidation and Vitamin E.
S. Rota, N. A. McWilliam, T. P. Baglin, and C. D. Byrne (1998)
Blood 91, 508-515
   Abstract »    Full Text »    PDF »
Cholesterol feeding reduces nuclear forms of sterol regulatory element binding proteins in hamster liver.
I. Shimomura, Y. Bashmakov, H. Shimano, J. D. Horton, J. L. Goldstein, and M. S. Brown (1997)
PNAS 94, 12354-12359
   Abstract »    Full Text »    PDF »
A targeted mutation in the murine gene encoding the high density lipoprotein (HDL) receptor scavenger receptor class B type I reveals its key role in HDL metabolism.
A. Rigotti, B. L. Trigatti, M. Penman, H. Rayburn, J. Herz, and M. Krieger (1997)
PNAS 94, 12610-12615
   Abstract »    Full Text »    PDF »
Liver LDL Receptor mRNA Expression Is Decreased in Human ApoB/CETP Double Transgenic Mice and Is Regulated by Diet as Well as the Cytokine Oncostatin M.
J. Liu, Y. L. Zhang, M. J. Spence, R. E. Vestal, P. M. Wallace, and D. S. Grass (1997)
Arterioscler Thromb Vasc Biol 17, 2948-2954
   Abstract »    Full Text »
Tamoxifen Decreases Cholesterol Sevenfold and Abolishes Lipid Lesion Development in Apolipoprotein E Knockout Mice.
J. Reckless, J. C. Metcalfe, and D. J. Grainger (1997)
Circulation 95, 1542-1548
   Abstract »    Full Text »
Changes in Plasma Lipoprotein Cholesterol Levels by Antisense Oligodeoxynucleotides against Cholesteryl Ester Transfer Protein in Cholesterol-fed Rabbits.
M. Sugano and N. Makino (1996)
J. Biol. Chem. 271, 19080-19083
   Abstract »    Full Text »    PDF »
Invited Review: From Diet to DNA: Dietary Patterning of Gene Expression.
M. M. McGrane and R. W. Hanson (1992)
Nutr Clin Pract 7, 16-21
   Abstract »    PDF »
Relationship between Expression Levels and Atherogenesis in Scavenger Receptor Class B, Type I Transgenics.
Y. Ueda, E. Gong, L. Royer, P. N. Cooper, O. L. Francone, and E. M. Rubin (2000)
J. Biol. Chem. 275, 20368-20373
   Abstract »    Full Text »    PDF »
Unsaturated Fatty Acids Down-regulate SREBP Isoforms 1a and 1c by Two Mechanisms in HEK-293 Cells.
V. C. Hannah, J. Ou, A. Luong, J. L. Goldstein, and M. S. Brown (2001)
J. Biol. Chem. 276, 4365-4372
   Abstract »    Full Text »    PDF »
Doubling Expression of the Low Density Lipoprotein Receptor by Truncation of the 3'-Untranslated Region Sequence Ameliorates Type III Hyperlipoproteinemia in Mice Expressing the Human ApoE2 Isoform.
C. Knouff, S. Malloy, J. Wilder, M. K. Altenburg, and N. Maeda (2001)
J. Biol. Chem. 276, 3856-3862
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)