Acute-phase serum amyloid A as a marker of insulin resistance in mice.
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.
Scheja
Ludger
L
Department of Biochemistry and Molecular Biology II, University Medical Center, 20246 Hamburg, Germany.
Heese
Barbara
B
Zitzer
Heike
H
Michael
Mervyn D
MD
Siesky
Angela M
AM
Pospisil
Heike
H
Beisiegel
Ulrike
U
Seedorf
Klaus
K
D041721:3T3-L1 Cells; D000210:Acute-Phase Reaction / Q000097:blood*; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology; D004195:Disease Models, Animal; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D020033:Protein Isoforms / Q000097:blood; D000685:Serum Amyloid A Protein / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D052242:Adiponectin; C499919:Adipoq protein, mouse; D015415:Biomarkers; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D004041:Dietary Fats; D051275:Glucose Transporter Type 4; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D020033:Protein Isoforms; C489995:Saa2 protein, mouse; C076498:Saa3 protein, mouse; D000685:Serum Amyloid A Protein; C495693:Slc2a4 protein, mouse