title: Increased lipid synthesis and decreased β-oxidation in the liver of SHR/NDmcr-cp (cp/cp) rats, an animal model of metabolic syndrome.
abstract: SHR/NDmcr-cp (cp/cp) rats (SHR/NDcp) are an animal model of metabolic syndrome. A previous study of ours revealed drastic increases in the mass of palmitic (16:0), oleic (18:1n-9), palmitoleic (16:1n-7), cis-vaccenic (18:1n-7) and 5,8,11-eicosatrienoic acids in the liver of SHR/NDcp. However, detailed information on the class of lipid accumulated and the mechanism responsible for the overproduction of the accumulated lipid in the liver was not obtained. This study aimed to characterize the class of lipid accumulated and to explore the mechanism underlying the lipid accumulation in the liver of SHR/NDcp, in comparison with SHR/NDmcr-cp (+/+) (lean hypertensive littermates of SHR/NDcp) and Wistar Kyoto rats. In the liver of SHR/NDcp, de novo synthesis of fatty acids (16:0, 18:1n-9 and 16:1n-7) and triacylglycerol (TAG) synthesis were up-regulated and fatty acid β-oxidation was down-regulated. These perturbations of lipid metabolism caused fat accumulation in hepatocytes and accumulation of TAG, which were enriched with 16:0, 18:1n-9 and 16:1n-7, in the liver of SHR/NDcp. On the other hand, no changes were found in hepatic contents of diacylglycerol and unesterified fatty acid (FFA); among FFA, there were no differences in the hepatic concentrations of unesterified 16:0 and stearic acid between SHR/NDcp and two other groups of rats. Moreover, little change was brought about in the expression of genes responsive to endoplasmic reticulum stress in the liver of SHR/NDcp. These results may reinforce the pathophysiological role of stearoyl-CoA desaturase 1 and fatty acid elongase 6 in the liver of SHR/NDcp.
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan.
authors.forename: Shizuyo
authors.initials: S
authors.lastname: Tanaka
authors.forename: Tohru
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Asano
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mitsumoto
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kobayashi
authors.forename: Naomi
authors.initials: N
authors.lastname: Kudo
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kawashima
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress; D004951:Esterification; D000081031:Fatty Acid Elongases; D005227:Fatty Acids / Q000378:metabolism*; D015870:Gene Expression; D050155:Lipogenesis; D008099:Liver / Q000378:metabolism*; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D014280:Triglycerides; D013230:Stearoyl-CoA Desaturase; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases
references.citation: Science. 2004 Oct 15;306(5695):457-61
references.pmid: 15486293
references.citation: NMR Biomed. 2009 Apr;22(3):310-7
references.pmid: 19012281
references.citation: Biochem Pharmacol. 1999 Sep 15;58(6):925-33
references.pmid: 10509745
references.citation: Mol Cell. 2000 Jul;6(1):77-86
references.pmid: 10949029
references.citation: Biochim Biophys Acta. 1995 Apr 6;1255(3):237-43
references.pmid: 7734438
references.citation: Eur J Pharmacol. 2009 Sep 15;618(1-3):28-36
references.pmid: 19616540
references.citation: Obesity (Silver Spring). 2007 Jan;15(1):24-31
references.pmid: 17228028
references.citation: Diabetologia. 2005 Oct;48(10):1999-2005
references.pmid: 16132958
references.citation: J Lipid Res. 2006 Sep;47(9):2028-41
references.pmid: 16790840
references.citation: Am J Physiol Endocrinol Metab. 2008 May;294(5):E969-77
references.pmid: 18349115
references.citation: J Biol Chem. 1951 Nov;193(1):265-75
references.pmid: 14907713
references.citation: J Lipid Res. 2001 Dec;42(12):2039-48
references.pmid: 11734577
references.citation: Exp Toxicol Pathol. 2012 May;64(4):333-8
references.pmid: 20965707
references.citation: Lipids. 2013 May;48(5):457-67
references.pmid: 23539346
references.citation: Can J Biochem Physiol. 1959 Aug;37(8):911-7
references.pmid: 13671378
references.citation: Biochim Biophys Acta. 2009 Jun;1791(6):501-6
references.pmid: 19038363
references.citation: Nature. 2011 May 26;473(7348):528-31
references.pmid: 21532591
references.citation: Obesity (Silver Spring). 2010 Jul;18(7):1460-3
references.pmid: 19875987
references.citation: Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3077-82
references.pmid: 12629214
references.citation: Hepatology. 2011 Jul;54(1):122-32
references.pmid: 21465509
references.citation: Am J Clin Nutr. 1984 Apr;39(4):612-8
references.pmid: 6369957
references.citation: J Biol Chem. 2009 Feb 27;284(9):5637-44
references.pmid: 19119140
references.citation: J Clin Invest. 2012 Jun;122(6):2176-94
references.pmid: 22546860
references.citation: Endocr Rev. 2008 Dec;29(7):939-60
references.pmid: 18723451
references.citation: Biol Pharm Bull. 2012;35(9):1509-15
references.pmid: 22975502
references.citation: Lipids. 1966 Jan;1(1):85-6
references.pmid: 17805690
references.citation: J Lipid Res. 2006 Sep;47(9):1928-39
references.pmid: 16751624
references.citation: Nat Med. 2007 Oct;13(10):1193-202
references.pmid: 17906635
references.citation: J Lipid Res. 2006 Dec;47(12):2668-80
references.pmid: 17005996
references.citation: Nat Clin Pract Endocrinol Metab. 2006 Jun;2(6):335-48
references.pmid: 16932311
references.citation: Science. 2006 Aug 25;313(5790):1137-40
references.pmid: 16931765
references.citation: Diabet Med. 2007 Jan;24(1):1-6
references.pmid: 17227317
references.citation: Anal Biochem. 1976 Apr;71(2):436-43
references.pmid: 5914
references.citation: Diabetes. 2001 Aug;50(8):1844-50
references.pmid: 11473047
references.citation: Curr Opin Clin Nutr Metab Care. 2010 Nov;13(6):703-8
references.pmid: 20823776
references.citation: Curr Opin Lipidol. 1997 Jun;8(3):146-53
references.pmid: 9211062
references.citation: Horm Res. 2007;68(2):72-82
references.pmid: 17344645
references.citation: Exp Mol Pathol. 1973 Aug;19(1):53-60
references.pmid: 4721724
references.citation: Acta Biochim Pol. 2010;57(4):389-92
references.pmid: 21079817
references.citation: J Biol Chem. 1999 Oct 15;274(42):30028-32
references.pmid: 10514488
references.citation: Prog Lipid Res. 2012 Oct;51(4):350-77
references.pmid: 22705711
references.citation: J Biol Chem. 2007 Jan 5;282(1):743-51
references.pmid: 17107947
references.citation: Biol Pharm Bull. 2012;35(2):184-91
references.pmid: 22293348
references.citation: J Hepatol. 2010 Apr;52(4):586-93
references.pmid: 20206402
references.citation: Clin Chem. 1964 May;10:451-3
references.pmid: 14185804
references.citation: Anal Biochem. 1980 May 1;104(1):118-23
references.pmid: 6770714
references.citation: Am J Physiol Endocrinol Metab. 2002 Jan;282(1):E46-51
references.pmid: 11739082
references.citation: Am J Pathol. 1975 Jul;80(1):129-42
references.pmid: 1171627
references.citation: Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):935-8
references.pmid: 7862668
references.citation: Int J Mol Med. 2008 Apr;21(4):507-11
references.pmid: 18360697
references.citation: Arch Biochem Biophys. 1978 Oct;190(2):409-20
references.pmid: 718160
references.citation: Life Sci. 2007 Jan 16;80(6):522-9
references.pmid: 17074368
references.citation: Nat Genet. 1996 Oct;14(2):130-1
references.pmid: 8841178
references.citation: Physiol Rev. 2010 Jan;90(1):367-417
references.pmid: 20086080
references.citation: Curr Opin Clin Nutr Metab Care. 2011 Mar;14(2):115-20
references.pmid: 21178610
references.citation: J Biol Chem. 2005 Jul 8;280(27):25629-36
references.pmid: 15878874
references.citation: Eur J Biochem. 1979 Jul;98(1):165-72
references.pmid: 467438
references.citation: Biochim Biophys Acta. 2010 Mar;1801(3):299-310
references.pmid: 19857603
references.citation: Am J Physiol Endocrinol Metab. 2006 Aug;291(2):E275-81
references.pmid: 16492686
references.citation: J Biochem. 1976 Aug;80(2):217-22
references.pmid: 1002667
references.citation: Am J Physiol. 1999 Apr;276(4):R1046-53
references.pmid: 10198384
references.citation: J Lipid Res. 2001 Jul;42(7):1018-24
references.pmid: 11441127
references.citation: J Clin Invest. 2009 May;119(5):1201-15
references.pmid: 19363290
references.citation: Jpn Circ J. 1963 Mar;27:282-93
references.pmid: 13939773
references.citation: Cell Metab. 2007 Dec;6(6):484-96
references.pmid: 18054317
references.citation: J Clin Invest. 2005 May;115(5):1343-51
references.pmid: 15864352