Serum amyloid A3 does not contribute to circulating SAA levels

• Published in: Journal of lipid research Vol. 50; no. 7; pp. 1353 - 1362
• Main Authors: Chiba, Tsuyoshi, Han, Chang Yeop, Vaisar, Tomas, Shimokado, Kentaro, Kargi, Atil, Chen, Mei-Hsiu, Wang, Shari, McDonald, Thomas O., O'Brien, Kevin D., Heinecke, Jay W, Chait, Alan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-07-2009; American Society for Biochemistry and Molecular Biology; Elsevier
• Subjects: 3T3-L1 Cells; adipose tissue; Adipose Tissue - metabolism; Animals; ApoE deficient mice; Apolipoproteins E - genetics; Apolipoproteins E - metabolism; Cholesterol - blood; gene expression; HDL; Humans; local inflammation; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese - genetics; Mice, Obese - metabolism; ob/ob mice; obesity; Obesity - metabolism; Serum Amyloid A Protein - genetics; Serum Amyloid A Protein - metabolism; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; systemic inflammation; ApoE deficient mice; HDL; systemic inflammation; adipose tissue; ob/ob mice; gene expression; local inflammation; obesity
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1194/jlr.M900089-JLR200

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.