Regulation of stearoyl-CoA desaturase expression.
Stearoyl-CoA desaturase (SCD) is a regulatory enzyme in lipogenesis, catalyzing the rate-limiting step in the overall de novo synthesis of monounsaturated FA, mainly oleate and palmitoleate from stearoyl- and palmitoyl-CoA, respectively. Oleate and palmitoleate are the major monounsaturated FA of membrane phospholipids, TG, wax esters, cholesterol esters, and alkyldiacylglycerol. Several SCD gene isoforms (SCD1, SCD2, SCD3, and SCD4) exist in mice, and two have been characterized in humans. SCD1 gene expression in liver cells is regulated by numerous stimuli including diet and hormones. We are interested in why SCD is such a highly regulated enzyme even though oleate, the major product of this enzyme, is one of the most abundant FA in the diet and is therefore readily available. Dietary oleate is also well known for its TG-lowering effects and, as a major component of olive oil, is expected to have beneficial effects. However, high SCD activity has been implicated in diabetes, obesity, atherosclerosis, and cancer in several animal models; therefore, the role that de novo oleate plays in these disease states has to be carefully evaluated. By using SCD1-/- mice, which are deficient in tissue oleate, we begin to learn more about the physiological role of SCD gene expression and oleate in normal and disease states.
Ntambi
James M
JM
Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA. ntambi@biochem.wisc.edu
Miyazaki
Makoto
M
Dobrzyn
Agnieszka
A
D000818:Animals; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*
D007527:Isoenzymes; D013230:Stearoyl-CoA Desaturase
Diabetes. 2002 Feb;51(2):271-5
11812732
Nat Med. 2002 Nov;8(11):1288-95
12368907
Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3077-82
12629214
Mamm Genome. 1998 Apr;9(4):341-2
9530639
Diabetes. 1997 Dec;46(12):2115-8
9392507
Proc Natl Acad Sci U S A. 1989 Aug;86(16):6133-7
2569740
J Physiol Paris. 2002 Apr-Jun;96(3-4):265-71
12445905
Brain Res. 2003 Jul 4;977(1):103-11
12788519
J Biol Chem. 2004 Aug 13;279(33):35017-24
15180999
Lipids. 1996 Mar;31 Suppl:S33-6
8729090
Prostaglandins Leukot Essent Fatty Acids. 2003 Feb;68(2):113-21
12538075
Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11482-6
12177411
J Biol Chem. 2003 Sep 5;278(36):33904-11
12815040
J Biol Chem. 1988 Nov 25;263(33):17291-300
2903162
J Biol Chem. 2000 Oct 20;275(42):32379-82
10934219
Biochim Biophys Acta. 1997 Apr 21;1345(3):349-57
9150254
Biochem J. 1999 May 15;340 ( Pt 1):255-64
10229681
J Neurochem. 2001 Nov;79(3):606-16
11701764
J Biol Chem. 2001 Mar 30;276(13):9800-7
11124951
J Biol Chem. 2001 Aug 3;276(31):28744-50
11397803
Biochem Biophys Res Commun. 1997 Apr 28;233(3):838-43
9168944
J Biol Chem. 1976 Aug 25;251(16):5095-103
8453
J Biol Chem. 1989 Sep 5;264(25):14755-61
2570068
J Biol Chem. 1996 Jan 26;271(4):2147-55
8567672
Science. 2002 Jul 12;297(5579):240-3
12114623
Prog Lipid Res. 1995;34(2):139-50
7480063
J Neurochem. 1998 Oct;71(4):1719-26
9751207
Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9443-8
8790349
Nature. 2002 Jan 17;415(6869):339-43
11797013
Genes Dev. 2000 Nov 15;14 (22):2819-30
11090130
J Biochem. 1990 Dec;108(6):1022-9
1982442
J Lipid Res. 1999 Sep;40(9):1549-58
10484602
J Biol Chem. 2001 Oct 19;276(42):39455-61
11500518
J Nutr. 2001 Sep;131(9):2260-8
11533264
J Biol Chem. 2000 Sep 15;275(37):28488-93
10862772
EMBO J. 1992 Feb;11(2):433-9
1537328
J Clin Invest. 1999 Jun;103(11):1489-98
10359558
Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6409-14
15096593
Gene. 2003 Apr 24;309(1):11-21
12727354
Biochemistry. 1978 Nov 14;17(23):4927-32
31169
J Lipid Res. 2001 Jul;42(7):1018-24
11441127
Biochem Biophys Res Commun. 1992 Jul 15;186(1):531-6
1352972
Cancer Res. 2000 Nov 15;60(22):6353-8
11103797
Genomics. 2001 Jan 15;71(2):182-91
11161812
Adv Exp Med Biol. 1999;466:79-85
10709630
J Biol Chem. 1994 Nov 4;269(44):27773-7
7961698
Curr Opin Lipidol. 2003 Jun;14(3):255-61
12840656
J Biol Chem. 1992 May 25;267(15):10925-30
1350282
J Biol Chem. 2001 Feb 9;276(6):4365-72
11085986
Biochem Biophys Res Commun. 1997 Feb 3;231(1):206-10
9070250
J Lipid Res. 2002 Oct;43(10):1750-7
12364560
J Lipid Res. 2002 Nov;43(11):1899-907
12401889
Trends Cardiovasc Med. 2004 Feb;14(2):77-81
15030794
J Lipid Res. 2004 Sep;45(9):1674-82
15210843
J Lipid Res. 2000 Aug;41(8):1310-6
10946019
J Lipid Res. 2002 Dec;43(12):2146-54
12454277
J Biol Chem. 2000 Sep 29;275(39):30132-8
10899171