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

Journal of Clinical Investigation

Volumn 101, Issue 11, 1998, Pages 2331-2339

  Norton, Jay D ^a   Shimomura, Iichiro ^a   Brown, Michael S ^a   Hammer, Robert E ^a,b   Goldstein, Joseph L ^a   Shimano, Hitoshi ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

Cholesterol; Fatty acids; Low density lipoprotein; Sterol regulatory element binding proteins; Transgenic mice

Indexed keywords

3 HYDROXY 3 METHYLGLUTARYL COENZYME A; BINDING PROTEIN; CHOLESTEROL; FATTY ACID; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE; LOW DENSITY LIPOPROTEIN; STEROL REGULATORY ELEMENT BINDING PROTEIN 2; UNCLASSIFIED DRUG;

ADIPOSE TISSUE; ARTICLE; CARBOXY TERMINAL SEQUENCE; CHOLESTEROL SYNTHESIS; FATTY ACID SYNTHESIS; GENE OVEREXPRESSION; LIVER; MALE; METABOLIC REGULATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; TRANSGENIC MOUSE;

EID: 0032104180     PISSN: 00219738     EISSN: None     Source Type: Journal    
DOI: 10.1172/jci2961     Document Type: Article

References (25)

1. Dietschy, J.M. 1997. Overview of cholesterol and lipoprotein metabolism in the brain, liver and extrahepatic organs. Nutr. Metab. Cardiovasc. Dis. 7:162-168.
2. Hillgartner, F.B., L.M. Salati, and A.G. Goodridge. 1995. Physiological and molecular mechanisms involved in nutritional regulation of fatty acid synthesis. Physiol. Rev. 75:47-76.
3. Brown, M.S., and J.L. Goldstein. 1997. The SREBP pathway: Regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell. 89:331-340.
4. Kim, J.B., G.D. Spotts, Y.-D. Halvorsen, H.-M. Shih, T. Ellenberger, H.C. Towle, and B.M. Spiegelman. 1995. Dual DNA binding specificity of ADD1/SREBP1 controlled by a single amino acid in the basic helix-loop-helix domain. Mol. Cell. Biol. 15:2582-2588.
5. Yokoyama, C., X. Wang, M.R. Briggs, A. Admon, J. Wu, X. Hua, J.L. Goldstein, and M.S. Brown. 1993. SREBP-1, a basic helix-loop-helix leucine zipper protein that controls transcription of the LDL receptor gene. Cell. 75: 187-197.
6. Hua, X., C. Yokoyama, J. Wu, M.R. Briggs, M.S. Brown, J.L. Goldstein, and X. Wang. 1993. SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element. Proc. Natl. Acad. Sci. USA. 90:11603-11607.
7. Ericsson, J., S.M. Jackson, B.C. Lee, and P.A. Edwards. 1996. Sterol regulatory element binding protein binds to a cis element in the promoter of the farnesyl diphosphate synthase gene. Proc. Natl. Acad. Sci. USA. 93:945-950.
8. Guan, G., P.-H. Dai, T.F. Osborne, J.B. Kim, and I. Shechter. 1997. Multiple sequence elements are involved in the transcriptional regulation of the human squalene synthase gene. J. Biol. Chem. 272:10295-10302.
9. Kim, J.B., and B.M. Spiegelman. 1996. ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism. Genes & Dev. 10:1096-1107.
10. Lopez, J.M., M.K. Bennett, H.B. Sanchez, J.M. Rosenfeld, and T.F. Osborne. 1996. Sterol regulation of acetyl CoA carboxylase: A mechanism for coordinate control of cellular lipid. Proc. Natl. Acad. Sci. USA. 93:1049-1053.
11. Ericsson, J., S.M. Jackson, J.B. Kim, B.M. Spiegelman, and P.A. Edwards. 1997. Identification of glycerol-3-phosphate acyltransferase as an adipocyte determination and differentiation factor 1 and sterol regulatory element-binding protein-responsive gene. J. Biol. Chem. 272:7298-7305.
12. Shimomura, I., H. Shimano, J.D. Horton, J.L. Goldstein, and M.S. Brown. 1997. Differential expression of exons 1a and 1c in mRNAs for sterol regulatory element binding protein-1 in human and mouse organs and cultured cells. J. Clin. Invest. 99:838-845.
13. Tontonoz, P., J.B. Kim, R.A. Graves, and B.M. Spiegelman. 1993. ADD1: a novel helix-loop-helix transcription factor associated with adipocyte determination and differentiation. Mol. Cell. Biol. 13:4753-4759.
14. Shimomura, I., Y. Bashmakov, H. Shimano, J.D. Horton, J.L. Goldstein, and M.S. Brown. 1997. Cholesterol feeding reduces nuclear forms of sterol regulatory element binding proteins in hamster liver. Proc. Natl. Acad. Sci. USA. 94:12354-12359.
15. Shimano, H., J.D. Horton, I. Shimomura, R.E. Hammer, M.S. Brown, and J.L. Goldstein. 1997. Isoform 1c of sterol regulatory element binding protein is less active than isoform 1a in livers of transgenic mice and in cultured cells. J. Clin. Invest. 99:846-854.
16. Shimano, H., J.D. Horton, R.E. Hammer, I. Shimomura, M.S. Brown, and J.L. Goldstein. 1996. Overproduction of cholesterol and fatty acids causes massive liver enlargement in transgenic mice expressing truncated SREBP-1a. J. Clin. Invest. 98:1575-1584.
17. Hamilton, J.G., and K. Comai. 1988. Rapid separation of neutral lipids, free fatty acids and polar lipids using prepacked silica Sep-pak columns. Lipids. 23:1146-1149.
18. Turley, S.D., M.W. Herndon, and J.M. Dietschy. 1994. Reevaluation and application of the dual-isotope plasma ratio method for the measurement of intestinal cholesterol absorption in the hamster. J. Lipid Res. 35:328-339.
19. Short, M.K., D.E. Clouthier, I.M. Schaefer, R.E. Hammer, M.A. Magnuson, and E.G. Beale. 1992. Tissue-specific, developmental, hormonal, and dietary regulation of rat phosphoenolpyruvate carboxykinase-human growth hormone fusion genes in transgenic mice. Mol. Cell. Biol. 12:1007-1020.
20. Chomczynski, P., and N. Sacchi. 1987. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162:156-159.
21. Shimano, H., I. Shimomura, R.E. Hammer, J. Herz, J.L. Goldstein, M.S. Brown, and J.D. Horton. 1997. Elevated levels of SREBP-2 and cholesterol synthesis in livers of mice homozygous for a targeted disruption of the SREBP-1 gene. J. Clin. Invest. 100:2115-2124.
22. Zhu, Y., K. Alvares, Q. Huang, M.S. Rao, and J.K. Reddy. 1993. Cloning of a new member of the peroxisome proliferator activated receptor gene family from mouse liver. J. Biol. Chem. 268:26817-26820.
23. Sato, R., J. Yang, X. Wang, M.J. Evans, Y.K. Ho, J.L. Goldstein, and M.S. Brown. 1994. Assignment of the membrane attachment, DNA binding, and transcriptional activation domains of sterol regulatory element binding protein-1 (SREBP-1). J. Biol. Chem. 269:17267-17273.
24. Sharp, D., L. Blinderman, K.A. Combs, B. Kienzle, B. Ricci, K. Wager-Smith, C.M. Gil, C.W. Turck, M.-E. Bouma, D.J. Rader, et al. 1993. Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinaemia. Nature. 365:65-69.
25. Sheng, Z., H. Otani, M.S. Brown, and J.L. Goldstein. 1995. Independent regulation of sterol regulatory element binding proteins 1 and 2 in hamster liver. Proc. Natl. Acad. Sci. USA. 92:935-938.