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Citations to this article

Activation of cholesterol synthesis in preference to fatty acid synthesis in liver and adipose tissue of transgenic mice overproducing sterol regulatory element-binding protein-2.
J D Horton, … , J L Goldstein, H Shimano
J D Horton, … , J L Goldstein, H Shimano
Published June 1, 1998
Citation Information: J Clin Invest. 1998;101(11):2331-2339. https://doi.org/10.1172/JCI2961.
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Research Article Article has an altmetric score of 12

Activation of cholesterol synthesis in preference to fatty acid synthesis in liver and adipose tissue of transgenic mice overproducing sterol regulatory element-binding protein-2.

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Abstract

We produced transgenic mice that express a dominant-positive truncated form of sterol regulatory element-binding protein-2 (SREBP-2) in liver and adipose tissue. The encoded protein lacks the membrane-binding and COOH-terminal regulatory domains, and it is therefore not susceptible to negative regulation by cholesterol. Livers from the transgenic mice showed increases in mRNAs encoding multiple enzymes of cholesterol biosynthesis, the LDL receptor, and fatty acid biosynthesis. The elevations in mRNA for 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) synthase and HMG CoA reductase were especially marked (13-fold and 75-fold, respectively). As a result, the transgenic livers showed a 28-fold increase in the rate of cholesterol synthesis and a lesser fourfold increase in fatty acid synthesis, as measured by intraperitoneal injection of [3H]water. These results contrast with previously reported effects of dominant-positive SREBP-1a, which activated fatty acid synthesis more than cholesterol synthesis. In adipose tissue of the SREBP-2 transgenics, the mRNAs for cholesterol biosynthetic enzymes were elevated, but the mRNAs for fatty acid biosynthetic enzymes were not. We conclude that SREBP-2 is a relatively selective activator of cholesterol synthesis, as opposed to fatty acid synthesis, in liver and adipose tissue of mice.

Authors

J D Horton, I Shimomura, M S Brown, R E Hammer, J L Goldstein, H Shimano

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1984 Total
Citations: 3 8 8 9 15 19 13 20 20 22 19 22 17 30 137 34 23 30 17 16 23 21 24 33 25 19 23 8 2 1 661
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Citations to this article in year 2006 (16)

Title and authors Publication Year
Primate-specific evolution of an LDLR enhancer
Q Wang, S Prabhakar, Q Wang, AM Moses, S Chanan, M Brown, MB Eisen, JF Cheng, EM Rubin, D Boffelli
Genome biology 2006
SREBP Activation by Antipsychotic- and Antidepressant-Drugs in Cultured Human Liver Cells: Relevance for Metabolic Side-Effects?
MB Raeder, J Fernø, AO Vik-Mo, VM Steen
Molecular and Cellular Biochemistry 2006
Carbohydrate response element binding protein, ChREBP, a transcription factor coupling hepatic glucose utilization and lipid synthesis
K Uyeda, JJ Repa
Cell Metabolism 2006
Androgen Activation of the Sterol Regulatory Element-Binding Protein Pathway: Current Insights
HV Heemers, G Verhoeven, JV Swinnen
Molecular Endocrinology 2006
Improving the fat content of foods
DI Shaw, WL Hall, CM Williams
Improving the fat content of foods 2006
ACAT1 deficiency increases cholesterol synthesis in mouse peritoneal macrophages
DE Dove, YR Su, LL Swift, MR Linton, S Fazio
Atherosclerosis 2006
Statins and hepatic steatosis: Perspectives from the Dallas Heart Study
JD Browning
Hepatology 2006
Antidepressant drugs activate SREBP and up-regulate cholesterol and fatty acid biosynthesis in human glial cells
MB Raeder, J Fernø, M Glambek, C Stansberg, VM Steen
Neuroscience Letters 2006
Schizochytrium limacinum SR-21 as a source of docosahexaenoic acid: optimal growth and use as a dietary supplement for laying hens
HJ Chin, TF Shen, HP Su, ST Ding
Australian Journal of Agricultural Research 2006
17β-Hydroxysteroid dehydrogenase type 7 (Hsd17b7) reverts cholesterol auxotrophy in NS0 cells
G Seth, RS McIvor, WS Hu
Journal of Biotechnology 2006
Changes in hepatic gene expression associated with the hypocholesterolaemic activity of royal jelly
M Kamakura, T Moriyama, T Sakaki
Journal of Pharmacy and Pharmacology 2006
p38 Mitogen-activated Protein Kinase Plays an Inhibitory Role in Hepatic Lipogenesis
Y Xiong, QF Collins, J An, E Lupo, HY Liu, D Liu, J Robidoux, Z Liu, W Cao
The Journal of biological chemistry 2006
Hepatic PCSK9 Expression Is Regulated by Nutritional Status via Insulin and Sterol Regulatory Element-binding Protein 1c
P Costet, B Cariou, G Lambert, F Lalanne, B Lardeux, AL Jarnoux, A Grefhorst, B Staels, M Krempf
The Journal of biological chemistry 2006
Increased cholesterol biosynthesis and hypercholesterolemia in mice overexpressing squalene synthase in the liver
H Okazaki, F Tazoe, S Okazaki, N Isoo, K Tsukamoto, M Sekiya, N Yahagi, Y Iizuka, K Ohashi, T Kitamine, R Tozawa, T Inaba, H Yagyu, M Okazaki, H Shimano, N Shibata, H Arai, R Nagai, T Kadowaki, J Osuga, S Ishibashi
Journal of lipid research 2006
A targeted apoB38.9 mutation in mice is associated with reduced hepatic cholesterol synthesis and enhanced lipid peroxidation
X Lin, Z Chen, P Yue, MR Averna, RE Ostlund, MA Watson, G Schonfeld
AJP Gastrointestinal and Liver Physiology 2006
Regulation of Adenosine 5′,Monophosphate-Activated Protein Kinase and Lipogenesis by Androgens Contributes to Visceral Obesity in an Estrogen-Deficient State
KJ McInnes, A Corbould, ER Simpson, ME Jones
Endocrinology 2006

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