HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, H.-J. Articles by Ntambi, J. M. Search for Related Content PubMed PubMed Citation Articles by Kim, H.-J. Articles by Ntambi, J. M. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 43, 1750-1757, October 2002
Copyright © 2002 by Lipid Research, Inc.

Dietary cholesterol opposes PUFA-mediated repression of the stearoyl-CoA desaturase-1 gene by SREBP-1 independent mechanism

Hyoun-Ju Kim^*, Makoto Miyazaki^* and James M. Ntambi^1,*,

^* Departments of Biochemistry, University of Wisconsin, Madison, Wisconsin, 53706
Nutritional Sciences, University of Wisconsin, Madison, Wisconsin, 53706

¹ To whom correspondence should be addressed. e-mail: ntambi{at}biochem.wisc.edu

Stearoyl-CoA desaturase (SCD) catalyzes the rate-limiting step in the cellular synthesis of monounsaturated fatty acids, mainly oleate (18:1) and palmitoleate (16:1), which are the major monounsaturated fatty acids of membrane phospholipids, cholesteryl esters, waxes, and triglycerides. The mouse expresses three well-characterized SCD genes (SCD1, 2, and 3). SCD1 is the main isoform expressed in the liver of mice. Previous in vivo studies have shown that the transcriptional repression by n-3 and n-6 polyunsaturated fatty acids (PUFAs) and the induction by cholesterol of the SCD1 gene are dependent on the maturation of the sterol regulatory element-binding protein-1c (SREBP-1c). We studied the regulation of SREBP-1, SCD1, and other SREBP-1 target genes when a high cholesterol diet is combined with PUFA as n-6 PUFA rich soybean oil (SO), or n-3 PUFA rich fish oil (FO). While the PUFA/cholesterol (PUFA/CH) diets repressed the maturation of the SREBP-1, the SCD1 mRNA levels, and protein and enzyme activity were induced. Compared with PUFA diets, hepatic cholesterol ester and triglyceride were enriched with 16:1 and 18:1 monounsaturated fatty acids in mice fed PUFA/CH diets. Total plasma cholesterol levels were not altered but plasma triglycerides were reduced in SO/CH-fed mice compared with SO-fed mice. The mRNA for SREBP-1 was increased by the PUFA/CH diet but the mRNA levels of SREBP-1 target genes such as fatty acid synthase and LDL receptor were decreased, indicating that the main control of PUFA-mediated suppression of SREBP-1 target genes is the maturation of SREBP-1.

This study demonstrates that cholesterol overrides the PUFA-mediated repression of the SCD1 gene and regulates SCD1 gene expression through a mechanism independent of SREBP-1 maturation.

Abbreviations: CE, cholesteryl ester; FAS, fatty acid synthase; LXR, liver X receptor; PUFA, polyunsaturated fatty acid; SCD, stearoyl-CoA desaturase; SREBP, sterol regulatory element-binding protein

Supplementary key words hepatic gene expression • cholesterol supplemented PUFA diet • fatty acid composition

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. M. Waters, J. P. Kelly, P. O'Boyle, A. P. Moloney, and D. A. Kenny Effect of level and duration of dietary n-3 polyunsaturated fatty acid supplementation on the transcriptional regulation of {Delta}9-desaturase in muscle of beef cattle J Anim Sci, January 1, 2009; 87(1): 244 - 252. [Abstract] [Full Text] [PDF]

				C. A. Major, K. Ryan, A. J. Bennett, A. L. Lock, D. E. Bauman, and A. M. Salter Inhibition of stearoyl CoA desaturase activity induces hypercholesterolemia in the cholesterol-fed hamster J. Lipid Res., July 1, 2008; 49(7): 1456 - 1465. [Abstract] [Full Text] [PDF]

				A. M. Hebbachi, B. L. Knight, D. Wiggins, D. D. Patel, and G. F. Gibbons Peroxisome Proliferator-activated Receptor {alpha} Deficiency Abolishes the Response of Lipogenic Gene Expression to Re-feeding: RESTORATION OF THE NORMAL RESPONSE BY ACTIVATION OF LIVER X RECEPTOR {alpha} J. Biol. Chem., February 22, 2008; 283(8): 4866 - 4876. [Abstract] [Full Text] [PDF]

				M. Torres-Gonzalez, S. Shrestha, M. Sharman, H. C. Freake, J. S. Volek, and M. L. Fernandez Carbohydrate Restriction Alters Hepatic Cholesterol Metabolism in Guinea Pigs Fed a Hypercholesterolemic Diet J. Nutr., October 1, 2007; 137(10): 2219 - 2223. [Abstract] [Full Text] [PDF]

				X. Qin, J. Tian, P. Zhang, Y. Fan, L. Chen, Y. Guan, Y. Fu, Y. Zhu, S. Chien, and N. Wang Laminar shear stress up-regulates the expression of stearoyl-CoA desaturase-1 in vascular endothelial cells Cardiovasc Res, June 1, 2007; 74(3): 506 - 514. [Abstract] [Full Text] [PDF]

				M. T. Flowers, A. K. Groen, A. T. Oler, M. P. Keller, Y. Choi, K. L. Schueler, O. C. Richards, H. Lan, M. Miyazaki, F. Kuipers, et al. Cholestasis and hypercholesterolemia in SCD1-deficient mice fed a low-fat, high-carbohydrate diet J. Lipid Res., December 1, 2006; 47(12): 2668 - 2680. [Abstract] [Full Text] [PDF]

				A. Baldan, P. Tarr, C. S. Vales, J. Frank, T. K. Shimotake, S. Hawgood, and P. A. Edwards Deletion of the Transmembrane Transporter ABCG1 Results in Progressive Pulmonary Lipidosis J. Biol. Chem., September 29, 2006; 281(39): 29401 - 29410. [Abstract] [Full Text] [PDF]

				K. Chu, M. Miyazaki, W. C. Man, and J. M. Ntambi Stearoyl-Coenzyme A Desaturase 1 Deficiency Protects against Hypertriglyceridemia and Increases Plasma High-Density Lipoprotein Cholesterol Induced by Liver X Receptor Activation. Mol. Cell. Biol., September 1, 2006; 26(18): 6786 - 6798. [Abstract] [Full Text] [PDF]

				T. Tanaka, S. Hidaka, H. Masuzaki, S. Yasue, Y. Minokoshi, K. Ebihara, H. Chusho, Y. Ogawa, T. Toyoda, K. Sato, et al. Skeletal Muscle AMP-Activated Protein Kinase Phosphorylation Parallels Metabolic Phenotype in Leptin Transgenic Mice Under Dietary Modification Diabetes, August 1, 2005; 54(8): 2365 - 2374. [Abstract] [Full Text] [PDF]

				R. R Almon, D. C DuBois, J. Y Jin, and W. J Jusko Temporal profiling of the transcriptional basis for the development of corticosteroid-induced insulin resistance in rat muscle J. Endocrinol., January 1, 2005; 184(1): 219 - 232. [Abstract] [Full Text] [PDF]

				F. Castro-Chavez, V. K. Yechoor, P. K. Saha, J. Martinez-Botas, E. C. Wooten, S. Sharma, P. O'Connell, H. Taegtmeyer, and L. Chan Coordinated Upregulation of Oxidative Pathways and Downregulation of Lipid Biosynthesis Underlie Obesity Resistance in Perilipin Knockout Mice: A Microarray Gene Expression Profile Diabetes, November 1, 2003; 52(11): 2666 - 2674. [Abstract] [Full Text] [PDF]

				M. Miyazaki, M. J. Jacobson, W. C. Man, P. Cohen, E. Asilmaz, J. M. Friedman, and J. M. Ntambi Identification and Characterization of Murine SCD4, a Novel Heart-specific Stearoyl-CoA Desaturase Isoform Regulated by Leptin and Dietary Factors J. Biol. Chem., September 5, 2003; 278(36): 33904 - 33911. [Abstract] [Full Text] [PDF]

				M.-Y. Akoume, S. Perwaiz, I. M. Yousef, and G. L. Plaa Synergistic Role of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase and Cholesterol 7{alpha}-Hydroxylase in the Pathogenesis of Manganese-Bilirubin-Induced Cholestasis in Rats Toxicol. Sci., June 1, 2003; 73(2): 378 - 385. [Abstract] [Full Text] [PDF]