title: No evidence for a role of adipose tissue-derived serum amyloid a in the development of insulin resistance or obesity-related inflammation in hSAA1(+/-) transgenic mice.
abstract: Obesity is associated with a low-grade inflammation including moderately increased serum levels of the acute phase protein serum amyloid A (SAA). In obesity, SAA is mainly produced from adipose tissue and serum levels of SAA are associated with insulin resistance. SAA has been described as a chemoattractant for inflammatory cells and adipose tissue from obese individuals contains increased numbers of macrophages. However, whether adipose tissue-derived SAA can have a direct impact on macrophage infiltration in adipose tissue or the development of insulin resistance is unknown. The aim of this study was to investigate the effects of adipose tissue-derived SAA1 on the development of insulin resistance and obesity-related inflammation. We have previously established a transgenic mouse model expressing human SAA1 in the adipose tissue. For this report, hSAA1(+/-) transgenic mice and wild type mice were fed with a high fat diet or normal chow. Effects of hSAA1 on glucose metabolism were assessed using an oral glucose tolerance test. Real-time PCR was used to measure the mRNA levels of macrophage markers and genes related to insulin sensitivity in adipose tissue. Cytokines during inflammation were analyzed using a Proinflammatory 7-plex Assay. We found similar insulin and glucose levels in hSAA1 mice and wt controls during an oral glucose tolerance test and no decrease in mRNA levels of genes related to insulin sensitivity in adipose tissue in neither male nor female hSAA1 animals. Furthermore, serum levels of proinflammatory cytokines and mRNA levels of macrophage markers in adipose tissue were not increased in hSAA1 mice. Hence, in this model we find no evidence that adipose tissue-derived hSAA1 influences the development of insulin resistance or obesity-related inflammation.
authors: Department of Molecular and Clinical Medicine, Institute of Medicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors: Sofie
authors: S
authors: Ahlin
authors: Maja
authors: M
authors: Olsson
authors: Bob
authors: B
authors: Olsson
authors: Per-Arne
authors: PA
authors: Svensson
authors: Kajsa
authors: K
authors: Sjöholm
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001786:Blood Glucose; D001823:Body Composition; D004195:Disease Models, Animal; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D007249:Inflammation / Q000209:etiology; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity / Q000150:complications / Q000235:genetics* / Q000378:metabolism*; D000685:Serum Amyloid A Protein / Q000235:genetics* / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; C521404:SAA1 protein, human; D000685:Serum Amyloid A Protein; D005947:Glucose
references: Amyloid. 2012 Mar;19(1):5-14
references: 22320226
references: Atherosclerosis. 2009 Dec;207(2):374-83
references: 19535079
references: Arterioscler Thromb Vasc Biol. 2000 Jun;20(6):1543-50
references: 10845870
references: Clin Biochem. 1994 Dec;27(6):469-73
references: 7535207
references: J Lipid Res. 2003 Dec;44(12):2257-69
references: 12951366
references: J Exp Med. 1999 Jan 18;189(2):395-402
references: 9892621
references: Diabetologia. 1997 Nov;40(11):1286-92
references: 9389420
references: Arterioscler Thromb Vasc Biol. 1999 Apr;19(4):972-8
references: 10195925
references: Front Immunol. 2013 Apr 22;4:92
references: 23626589
references: J Lipid Res. 2002 Sep;43(9):1410-20
references: 12235172
references: PLoS One. 2011;6(5):e19609
references: 21611116
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: Lab Invest. 1992 Jun;66(6):778-85
references: 1602745
references: Ann N Y Acad Sci. 1982;389:183-9
references: 7046575
references: Mol Med. 2011;17(11-12):1357-64
references: 21953420
references: Diabetologia. 1999 Dec;42(12):1433-8
references: 10651262
references: Arthritis Rheum. 2013 Jan;65(1):283-4
references: 23044993
references: J Clin Invest. 1978 Feb;61(2):390-4
references: 621279
references: Biochim Biophys Acta. 1997 Apr 25;1339(1):143-54
references: 9165109
references: J Clin Endocrinol Metab. 2005 Apr;90(4):2233-9
references: 15623807
references: J Clin Invest. 2003 Dec;112(12):1821-30
references: 14679177
references: Diabetologia. 2002 Jun;45(6):805-12
references: 12107724
references: J Lipid Res. 1997 Aug;38(8):1583-90
references: 9300780
references: Lancet. 2005 Oct 1;366(9492):1197-209
references: 16198769
references: J Intern Med. 2009 Sep;266(3):286-95
references: 19702793
references: Arthritis Rheum. 2010 Jun;62(6):1660-5
references: 20201074
references: J Biol Chem. 1986 Jul 25;261(21):9644-51
references: 3525531
references: J Endocrinol Invest. 2009 Jul;32(7):568-75
references: 19474523
references: J Immunol. 1995 Jan 15;154(2):825-31
references: 7814886
references: Curr Atheroscler Rep. 2006 Jan;8(1):62-8
references: 16455016
references: JAMA. 1999 Oct 27;282(16):1523-9
references: 10546691
references: J Exp Med. 1994 Jul 1;180(1):203-9
references: 7516407
references: PLoS One. 2012;7(4):e34031
references: 22532826
references: J Clin Invest. 2006 Jun;116(6):1494-505
references: 16691291
references: Exp Diabetes Res. 2008;2008:230837
references: 18584041
references: Blood. 2006 Sep 1;108(5):1751-7
references: 16735604
references: Cytokine. 2009 Dec;48(3):260-6
references: 19758820
references: PLoS Med. 2006 Jun;3(6):e287
references: 16737350
references: J Clin Invest. 2003 Dec;112(12):1796-808
references: 14679176
references: J Clin Endocrinol Metab. 2000 Sep;85(9):3338-42
references: 10999830
references: JAMA. 1999 Dec 8;282(22):2131-5
references: 10591334
references: J Clin Endocrinol Metab. 1998 Aug;83(8):2907-10
references: 9709967
references: Diabetologia. 2005 Mar;48(3):519-28
references: 15729583