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
Department of Medicine, University of Washington, Seattle, Washington, USA.
J Lipid Res. 2009 Jul;50(7):1353-62. doi: 10.1194/jlr.M900089-JLR200. Epub 2009 Mar 12.
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.
脂肪组织会分泌诸如血清淀粉样蛋白A（SAA）之类的蛋白质，其在局部和全身炎症中发挥重要作用。肥胖人群的循环SAA水平会升高，但脂肪源性SAA和高脂血症在此过程中的作用尚不清楚。我们利用小鼠脂肪组织（SAA3）和肝脏（SAA1和2）分泌的SAA诱导型异构体的差异，来评估脂肪组织是否在肥胖和高脂血症中对SAA的循环池有贡献。遗传性肥胖（ob/ob）小鼠而非载脂蛋白E缺乏的高脂血症小鼠（Apoe(-/-)），其循环SAA水平显著高于同窝对照。肥胖小鼠肝脏中的SAA1/2 mRNA表达以及腹部脂肪中的SAA3 mRNA表达均显著高于瘦小鼠，但在Apoe(-/-)小鼠中它们不受高脂血症影响。然而，通过对循环SAA的主要载体HDL进行质谱分析，在循环中仅能检测到SAA1/2和SAA的组成型形式（SAA4）。相反，在培养的脂肪细胞培养基中可检测到SAA3。我们的研究结果表明，肥胖会使脂肪组织中SAA3的表达上调，但它对小鼠SAA的循环池没有贡献。
