title: Up-regulation of stearoyl-CoA desaturase 1 increases liver MUFA content in obese Zucker but not Goto-Kakizaki rats.
abstract: The Goto-Kakizaki (GK) rat is an animal model for spontaneous-onset, non-obese type 2 diabetes. Despite abundant evidence about disorders in metabolism, little information is available about fatty acid metabolism in the liver of GK rats. This study aimed to investigate the characteristics of the fatty acid profile, particularly MUFA, and the mechanism underlying the alterations in fatty acid profiles in the liver of GK rats. The activities of enzymes that participate in the biosynthesis of MUFA, expressions of genes encoding these enzymes, and the fatty acid profile in the liver were compared with those of obese Zucker (fa/fa) (ZF) rats, which are obese and non-diabetic. Stearoyl-CoA desaturase (SCD) activity and SCD1 gene expression were considerably up-regulated in GK rats, and these levels were largely comparable to those in ZF rats. However, the proportions and contents of oleic acid and palmitoleic acid were very low considering the highly elevated activity of SCD in the liver of GK rats, when compared with ZF rats. Palmitoyl-CoA chain elongation (PCE) activity and fatty acid elongase (Elovl6) gene expression were markedly up-regulated in ZF rats, whereas PCE activity was up-regulated much less and Elovl6 gene expression was unchanged in GK rats. These results suggest the possibility that up-regulation of gene expression of Elovl6 along with SCD1 is indispensable to elevate the proportions and contents of oleic acid in the liver.
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Karahashi
authors.forename: Fumiko
authors.initials: F
authors.lastname: Ishii
authors.forename: Tohru
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Koichi
authors.initials: K
authors.lastname: Imai
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mitsumoto
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kawashima
authors.forename: Naomi
authors.initials: N
authors.lastname: Kudo
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D000081031:Fatty Acid Elongases; D005229:Fatty Acids, Monounsaturated / Q000032:analysis / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D013230:Stearoyl-CoA Desaturase / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D005229:Fatty Acids, Monounsaturated; D013230:Stearoyl-CoA Desaturase; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases
references.citation: Cell. 1996 Feb 9;84(3):491-5
references.pmid: 8608603
references.citation: J Lipid Res. 2010 Mar;51(3):500-13
references.pmid: 19783528
references.citation: Biochim Biophys Acta. 1968 Sep 2;164(1):25-34
references.pmid: 5680293
references.citation: J Biol Chem. 2008 Nov 28;283(48):33772-83
references.pmid: 18835813
references.citation: J Biol Chem. 1991 Mar 15;266(8):5080-6
references.pmid: 1848237
references.citation: J Lipid Res. 2006 Sep;47(9):2028-41
references.pmid: 16790840
references.citation: Am J Physiol Endocrinol Metab. 2006 Aug;291(2):E275-81
references.pmid: 16492686
references.citation: Biol Pharm Bull. 2012;35(1):116-20
references.pmid: 22223347
references.citation: Am J Physiol Endocrinol Metab. 2009 Dec;297(6):E1291-303
references.pmid: 19755671
references.citation: Science. 2004 Oct 15;306(5695):457-61
references.pmid: 15486293
references.citation: Exp Toxicol Pathol. 2012 May;64(4):333-8
references.pmid: 20965707
references.citation: Cell. 2008 Sep 19;134(6):933-44
references.pmid: 18805087
references.citation: Am J Physiol Gastrointest Liver Physiol. 2010 Oct;299(4):G855-66
references.pmid: 20595619
references.citation: Prog Lipid Res. 2004 Mar;43(2):91-104
references.pmid: 14654089
references.citation: J Mol Med (Berl). 2009 Apr;87(4):379-84
references.pmid: 19259639
references.citation: Can J Biochem Physiol. 1959 Aug;37(8):911-7
references.pmid: 13671378
references.citation: J Biol Chem. 2009 Feb 27;284(9):5637-44
references.pmid: 19119140
references.citation: Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3077-82
references.pmid: 12629214
references.citation: J Clin Invest. 2008 Jan;118(1):316-32
references.pmid: 18060040
references.citation: Biol Pharm Bull. 2012;35(9):1509-15
references.pmid: 22975502
references.citation: Hepatology. 2007 Jul;46(1):122-9
references.pmid: 17526015
references.citation: Lipids. 2003 May;38(5):531-7
references.pmid: 12880109
references.citation: Nat Med. 2007 Oct;13(10):1193-202
references.pmid: 17906635
references.citation: Biochem Biophys Res Commun. 1994 Nov 30;205(1):417-22
references.pmid: 7999057
references.citation: J Biol Chem. 2000 Sep 29;275(39):30132-8
references.pmid: 10899171
references.citation: Expert Rev Gastroenterol Hepatol. 2009 Aug;3(4):445-51
references.pmid: 19673631
references.citation: J Lipid Res. 2013 Jan;54(1):71-84
references.pmid: 23099444
references.citation: Diabetes. 1991 Apr;40(4):486-91
references.pmid: 2010050
references.citation: Int J Clin Exp Med. 2010 Sep 27;3(4):303-7
references.pmid: 21072264
references.citation: Biol Pharm Bull. 2012;35(2):184-91
references.pmid: 22293348
references.citation: Biochim Biophys Acta. 1982 Dec 13;713(3):622-8
references.pmid: 6129897
references.citation: J Hepatol. 2010 Apr;52(4):586-93
references.pmid: 20206402
references.citation: J Pharmacol Sci. 2007 Jun;104(2):137-45
references.pmid: 17538229
references.citation: PLoS One. 2012;7(6):e39286
references.pmid: 22768070
references.citation: J Nutr. 1997 Feb;127(2):249-56
references.pmid: 9039824
references.citation: Biochim Biophys Acta. 1985 Mar 27;834(1):118-23
references.pmid: 3884049
references.citation: Diabetes Metab Res Rev. 2005 Nov-Dec;21(6):495-504
references.pmid: 15926190
references.citation: J Lipid Res. 1995 Aug;36(8):1676-85
references.pmid: 7595089
references.citation: Prog Lipid Res. 2010 Apr;49(2):186-99
references.pmid: 20018209
references.citation: Crit Rev Biochem Mol Biol. 2010 Jun;45(3):199-214
references.pmid: 20218765
references.citation: Nat Genet. 1996 May;13(1):18-9
references.pmid: 8673096
references.citation: J Clin Invest. 2006 Jun;116(6):1686-95
references.pmid: 16741579
references.citation: J Biol Chem. 2006 Apr 28;281(17):12093-101
references.pmid: 16505490
references.citation: Biochim Biophys Acta. 2011 Jun;1811(6):409-17
references.pmid: 21172452
references.citation: J Lipid Res. 2010 Jul;51(7):1871-7
references.pmid: 20228221
references.citation: Curr Opin Clin Nutr Metab Care. 2011 Mar;14(2):115-20
references.pmid: 21178610
references.citation: Diabetologia. 2008 Apr;51(4):648-56
references.pmid: 18286258
references.citation: Lipids. 1989 May;24(5):389-95
references.pmid: 2755316
references.citation: J Lipid Res. 2005 Apr;46(4):706-15
references.pmid: 15654130
references.citation: J Biol Chem. 2002 Jan 18;277(3):1705-11
references.pmid: 11694526
references.citation: Cell Metab. 2007 Dec;6(6):484-96
references.pmid: 18054317
references.citation: J Biol Chem. 2010 Jul 16;285(29):22027-35
references.pmid: 20489212
references.citation: Endocrinology. 1983 Apr;112(4):1346-51
references.pmid: 6339203
references.citation: Mol Cell Biochem. 2009 Nov;331(1-2):31-40
references.pmid: 19444596
references.citation: J Biol Chem. 1951 Nov;193(1):265-75
references.pmid: 14907713
references.citation: Biochim Biophys Acta. 2010 Mar;1801(3):338-49
references.pmid: 20056169
references.citation: Am J Physiol. 1993 Nov;265(5 Pt 1):E807-13
references.pmid: 8238507