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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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Citations to this article in year 2019 (13)

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SH Rouschop, T Karl, A Risch, PA van Ewijk, VB Schrauwen-Hinderling, A Opperhuizen, FJ van Schooten, RW Godschalk
Journal of lipid research 2019
Hepatic Transcriptomics Reveals that Lipogenesis Is a Key Signaling Pathway in Isocitrate Dehydrogenase 2 Deficient Mice
JH Pan, J Tang, MC Redding, KE Beane, CL Conner, YJ Cho, J Zhao, JH Kim, BC Kong, JH Lee, JK Kim
Genes & development 2019
Intracutaneous Delivery of Gelatins Reduces Fat Accumulation in Subcutaneous Adipose Tissue
SM An, MJ Kim, KY Seong, JS Jeong, HG Kang, SY Kim, DS Kim, DH Kang, SY Yang, BS An
Toxicological Research 2019
Frequent modulation of the sterol regulatory element binding protein (SREBP) by chemical exposure in the livers of rats
JC Corton
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J Shi, R Li, Y Liu, H Lu, L Yu, F Zhang
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K Nohara, T Nemkov, A DAlessandro, SH Yoo, Z Chen
International journal of molecular sciences 2019

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S Yamasaki, T Tomihara, G Kimura, Y Ueno, RM Ketema, S Sato, Y Mukai, T Sikder, M Kurasaki, T Hosokawa, T Saito
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