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Diet-Induced Hypercholesterolemia in Mice: Prevention by Overexpression of LDL Receptors
Abstract
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.
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“Overexpression of LDLR in the liver facilitated LDL elimination by receptor-mediated endocytosis and prevented diet-induced hypercholesterolemia (Hofmann et al., 1988; Yokode et al., 1990).”
From Overexpression of Low-Density Lipoprotein Receptor in the Brain Markedly Inhibits Amyloid Deposition and Increases Extracellular Aβ Clearance (2009) · cites this paper as Yokode et al., 1990
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Metadata
- Authors
- Yokode, M., Hammer, R. E., Ishibashi, S., Brown, M. S., & Goldstein, J. L.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Howard Hughes Medical Institute (US)
- Venue
- Science
- Published
- 1990-11-30
- Volume
- 250
- Issue
- 4985
- Pages
- 1273-1275
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2059352674
- Cited by
- 175
- References
- 28
- Citations by year
- 2024: 1 · 2021: 3 · 2020: 1 · 2019: 4 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 2 · 2012: 3
- FWCI
- 18.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-20948, P01HL020948)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- LDL receptor, hypercholesterolemia, high-fat diet, transgenic mice, liver, LDL cholesterol, bile acids, cholesterol, saturated fat, gene overexpression
- MeSH terms
- Animals, Cholesterol, Dietary, Dietary Fats, Exons, Humans, Hypercholesterolemia, Introns, Lipoproteins, Lipoproteins, HDL, Cholesterol, LDL, Lipoproteins, VLDL, Liver, Mice, Inbred C57BL, Mice, Transgenic, Nucleic Acid Hybridization, Promoter Regions, Genetic, Receptors, LDL, RNA, Messenger, Transferrin, Gene Expression, Mice, Lipoproteins, IDL
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