title: Establishment of a transgenic mouse model specifically expressing human serum amyloid A in adipose tissue.
abstract: Obesity and obesity co-morbidities are associated with a low grade inflammation and elevated serum levels of acute phase proteins, including serum amyloid A (SAA). In the non-acute phase in humans, adipocytes are major producers of SAA but the function of adipocyte-derived SAA is unknown. To clarify the role of adipocyte-derived SAA, a transgenic mouse model expressing human SAA1 (hSAA) in adipocytes was established. hSAA expression was analysed using real-time PCR analysis. Male animals were challenged with a high fat (HF) diet. Plasma samples were subjected to fast protein liquid chromatography (FPLC) separation. hSAA, cholesterol and triglyceride content were measured in plasma and in FPLC fractions. Real-time PCR analysis confirmed an adipose tissue-specific hSAA gene expression. Moreover, the hSAA gene expression was not influenced by HF diet. However, hSAA plasma levels in HF fed animals (37.7±4.0 µg/mL, n = 7) were increased compared to those in normal chow fed animals (4.8±0.5 µg/mL, n = 10; p<0.001), and plasma levels in the two groups were in the same ranges as in obese and lean human subjects, respectively. In FPLC separated plasma samples, the concentration of hSAA peaked in high-density lipoprotein (HDL) containing fractions. In addition, cholesterol distribution over the different lipoprotein subfractions as assessed by FPLC analysis was similar within the two experimental groups. The established transgenic mouse model demonstrates that adipose tissue produced hSAA enters the circulation, resulting in elevated plasma levels of hSAA. This new model will enable further studies of metabolic effects of adipose tissue-derived SAA.
authors: Sahlgrenska Center for Cardiovascular and Metabolic Research, Institute of Medicine at the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. maja.olsson@gu.se
authors: Maja
authors: M
authors: Olsson
authors: Sofie
authors: S
authors: Ahlin
authors: Bob
authors: B
authors: Olsson
authors: Per-Arne
authors: PA
authors: Svensson
authors: Marcus
authors: M
authors: Ståhlman
authors: Jan
authors: J
authors: Borén
authors: Lena M S
authors: LM
authors: Carlsson
authors: Kajsa
authors: K
authors: Sjöholm
references: Genes Dev. 2000 Apr 15;14(8):963-80
references: 10783168
references: Obesity (Silver Spring). 2010 Jan;18(1):35-41
references: 19498343
references: J Clin Endocrinol Metab. 2009 May;94(5):1810-7
references: 19223523
references: J Lipid Res. 2003 Apr;44(4):780-92
references: 12562837
references: J Lipid Res. 2010 Nov;51(11):3117-25
references: 20667817
references: J Clin Invest. 1995 May;95(5):2246-57
references: 7738190
references: J Lipid Res. 2004 Feb;45(2):317-25
references: 14595002
references: Obesity (Silver Spring). 2006 Feb;14(2):309-18
references: 16571858
references: J Biol Chem. 2006 Sep 8;281(36):26602-14
references: 16809344
references: Circulation. 2004 Aug 3;110(5):540-5
references: 15277327
references: Diabetologia. 2005 Mar;48(3):519-28
references: 15729583
references: Curr Opin Lipidol. 2007 Apr;18(2):147-51
references: 17353662
references: Immunol Lett. 2007 Feb 15;108(2):160-6
references: 17267050
references: Nephrology (Carlton). 2007 Feb;12(1):25-32
references: 17295657
references: Circulation. 2004 Feb 17;109(6):726-32
references: 14970107
references: FASEB J. 2006 Jul;20(9):1540-2
references: 16754744
references: JAMA. 2009 Jul 1;302(1):37-48
references: 19567438
references: J Biol Chem. 1999 Mar 12;274(11):7172-81
references: 10066777
references: Arterioscler Thromb Vasc Biol. 2000 Jun;20(6):1543-50
references: 10845870
references: J Lipid Res. 2009 Jul;50(7):1353-62
references: 19286646
references: Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11371-6
references: 11027337
references: J Clin Endocrinol Metab. 2005 Apr;90(4):2233-9
references: 15623807
references: J Lipid Res. 2008 Feb;49(2):481-90
references: 18025001
references: J Nutr Biochem. 2010 Apr;21(4):317-24
references: 19369048
references: N Engl J Med. 1999 Oct 7;341(15):1097-105
references: 10511607
references: J Biol Chem. 2004 Aug 20;279(34):35503-9
references: 15190075
references: Am J Pathol. 2008 Dec;173(6):1902-10
references: 18974302
references: J Intern Med. 2009 Sep;266(3):286-95
references: 19702793
references: Eur J Biochem. 1999 Oct;265(2):501-23
references: 10504381
references: J Clin Invest. 1968 Jan;47(1):153-65
references: 16695937
references: J Exp Med. 1999 Jan 18;189(2):395-402
references: 9892621
references: J Histochem Cytochem. 1998 Dec;46(12):1377-84
references: 9815279
references: J Biol Chem. 1986 Jul 25;261(21):9644-51
references: 3525531
references: Atherosclerosis. 2008 Jan;196(1):248-255
references: 17588586
references: Nat Med. 2001 Jun;7(6):699-705
references: 11385507
references: Arterioscler Thromb Vasc Biol. 1999 Apr;19(4):972-8
references: 10195925
references: Arterioscler Thromb Vasc Biol. 2005 Apr;25(4):785-90
references: 15692094
references: J Lipid Res. 2010 Apr;51(4):743-54
references: 20061576
references: Proc Natl Acad Sci U S A. 1977 Sep;74(9):4025-8
references: 198813
references: Cytokine. 2009 Dec;48(3):260-6
references: 19758820
references: Biol Pharm Bull. 2008 Jul;31(7):1415-21
references: 18591785
references: Exp Diabetes Res. 2008;2008:230837
references: 18584041
references: Proc Natl Acad Sci U S A. 1990 Dec;87(24):9590-4
references: 2263614
references: J Atheroscler Thromb. 2009 Jun;16(3):299-300
references: 19556718
references: N Engl J Med. 2000 Mar 23;342(12):836-43
references: 10733371
references: Circ J. 2007 Feb;71(2):186-90
references: 17251664
references: PLoS Med. 2006 Jun;3(6):e287
references: 16737350
references: J Lipid Res. 1999 Apr;40(4):648-53
references: 10191288
references: Diabetes. 2007 Sep;56(9):2260-73
references: 17563062