acute-phase serum amyloid a as a marker of insulin resistance in mice急性期血清淀粉样蛋白小鼠胰岛素抵抗的标志.pdfVIP

Hindawi Publishing Corporation Experimental Diabetes Research Volume 2008, Article ID 230837, 11 pages doi:10.1155/2008/230837 Research Article Acute-Phase Serum Amyloid A as a Marker of Insulin Resistance in Mice Ludger Scheja,1, 2 Barbara Heese,1, 2 Heike Zitzer,2 Mervyn D. Michael,3 Angela M. Siesky,3 Heike Pospisil,4 Ulrike Beisiegel,1 and Klaus Seedorf1, 2 1 Department of Biochemistry and Molecular Biology II, University Medical Center, 20246 Hamburg, Germany 2 Former Lilly Research Laboratories, 22419 Hamburg, Germany 3 Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA 4 Center for Bioinformatics, University of Hamburg, 20146 Hamburg, Germany Correspondence should be addressed to Ludger Scheja, l.scheja@uke.uni-hamburg.de Received 21 November 2007; Revised 3 March 2008; Accepted 29 April 2008 Recommended by Eleazar Shafrir 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 alteration