Scheja Ludger, Heese Barbara, Zitzer Heike, Michael Mervyn D, Siesky Angela M, Pospisil Heike, Beisiegel Ulrike, Seedorf Klaus
Department of Biochemistry and Molecular Biology II, University Medical Center, 20246 Hamburg, Germany.
Exp Diabetes Res. 2008;2008:230837. doi: 10.1155/2008/230837.
Acute-phase serum amyloid A (A-SAA) was shown recently to correlate with obesity and insulin resistance in humans. However, the mechanisms linking obesity-associated inflammation and elevated plasma A-SAA to insulin resistance are poorly understood. Using high-fat diet- (HFD-) fed mice, we found that plasma A-SAA was increased early upon HFD feeding and was tightly associated with systemic insulin resistance. Plasma A-SAA elevation was due to induction of Saa1 and Saa2 expression in liver but not in adipose tissue. In adipose tissue Saa3 was the predominant isoform and the earliest inflammatory marker induced, suggesting it is important for initiation of adipose tissue inflammation. To assess the potential impact of A-SAA on adipose tissue insulin resistance, we treated 3T3-L1 adipocytes with recombinant A-SAA. Intriguingly, physiological levels of A-SAA caused alterations in gene expression closely resembling those observed in HFD-fed mice. Proinflammatory genes (Ccl2, Saa3) were induced while genes critical for insulin sensitivity (Irs1, Adipoq, Glut4) were down-regulated. Our data identify HFD-fed mice as a suitable model to study A-SAA as a biomarker and a novel possible mediator of insulin resistance.
近期研究表明，急性期血清淀粉样蛋白A（A-SAA）与人类肥胖及胰岛素抵抗相关。然而，肥胖相关炎症及血浆A-SAA升高与胰岛素抵抗之间的联系机制尚不清楚。我们使用高脂饮食（HFD）喂养的小鼠，发现喂食HFD后早期血浆A-SAA升高，且与全身胰岛素抵抗密切相关。血浆A-SAA升高是由于肝脏中Saa1和Saa2表达的诱导，而非脂肪组织。在脂肪组织中，Saa3是主要的亚型且是最早诱导的炎症标志物，表明其对脂肪组织炎症的起始很重要。为评估A-SAA对脂肪组织胰岛素抵抗的潜在影响，我们用重组A-SAA处理3T3-L1脂肪细胞。有趣的是，生理水平的A-SAA导致基因表达改变，与HFD喂养小鼠中观察到的情况非常相似。促炎基因（Ccl2、Saa3）被诱导，而对胰岛素敏感性至关重要的基因（Irs1、Adipoq、Glut4）被下调。我们的数据表明，HFD喂养的小鼠是研究A-SAA作为胰岛素抵抗生物标志物和新型潜在介质的合适模型。
