title: Serum amyloid A3 does not contribute to circulating SAA levels.
abstract: Adipose tissue secretes proteins like serum amyloid A (SAA), which plays important roles in local and systemic inflammation. Circulating SAA levels increase in obese humans, but the roles of adipose-derived SAA and hyperlipidemia in this process are unclear. We took advantage of the difference in the inducible isoforms of SAA secreted by adipose tissue (SAA3) and liver (SAA1 and 2) of mice to evaluate whether adipose tissue contributes to the circulating pool of SAA in obesity and hyperlipidemia. Genetically obese (ob/ob) mice, but not hyperlipidemic mice deficient in apolipoprotein E (Apoe(-/-)), had significantly higher circulating levels of SAA than their littermate controls. SAA1/2 mRNA expression in the liver and SAA3 mRNA expression in intra-abdominal fat were significantly higher in obese than thin mice, but they were not affected by hyperlipidemia in Apoe(-/-) mice. However, only SAA1/2 and the constitutive form of SAA (SAA4) could be detected in the circulation by mass spectrometric analysis of HDL, the major carrier of circulating SAA. In contrast, SAA3 could be detected in medium from cultured adipocytes. Our findings indicate that the expression of SAA3 in adipose tissue is upregulated by obesity, but it does not contribute to the circulating pool of SAA in mice.
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Chiba
authors.forename: Chang Yeop
authors.initials: CY
authors.lastname: Han
authors.forename: Tomas
authors.initials: T
authors.lastname: Vaisar
authors.forename: Kentaro
authors.initials: K
authors.lastname: Shimokado
authors.forename: Atil
authors.initials: A
authors.lastname: Kargi
authors.forename: Mei-Hsiu
authors.initials: MH
authors.lastname: Chen
authors.forename: Shari
authors.initials: S
authors.lastname: Wang
authors.forename: Thomas O
authors.initials: TO
authors.lastname: McDonald
authors.forename: Kevin D
authors.initials: KD
authors.lastname: O'Brien
authors.forename: Jay W
authors.initials: JW
authors.lastname: Heinecke
authors.forename: Alan
authors.initials: A
authors.lastname: Chait
mesh_terms: D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000235:genetics / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D001057:Apolipoproteins E; C076498:Saa3 protein, mouse; D000685:Serum Amyloid A Protein; D002784:Cholesterol