title: Adiponectin decreases C-reactive protein synthesis and secretion from endothelial cells: evidence for an adipose tissue-vascular loop.
abstract: OBJECTIVE
  Inflammation is pivotal in atherosclerosis. C-reactive protein (CRP), in addition to being a cardiovascular risk marker, may also be proatherogenic. We have previously shown that in addition to the liver, human aortic endothelial cells (HAECs) synthesize and secrete CRP. Whereas CRP levels are increased in obesity, metabolic syndrome, and diabetes, levels of adiponectin are reduced in these conditions. We tested the hypothesis that adiponectin reduces CRP synthesis and secretion in HAECs under normoglycemic (5.5 mmol/L glucose) and hyperglycemic conditions (15 mmol/L glucose).
  
  
  RESULTS
  Adiponectin dose-dependently reduced CRP mRNA and protein from HAECs. Adiponectin treatment of HAECs significantly decreased IkappaB phosphorylation and NFkappaB binding activity. There was no effect of adiponectin on STAT or C/EBP transcriptional activity. Adiponectin also activated AMP kinase resulting in decreased NFkappaB activity and decreased CRP mRNA and protein. These effects of adiponectin were mimicked by AICAR, an activator of AMPK, and reversed by inhibition of AMPK. Thus, adiponectin reduces CRP synthesis and secretion from HAECs under hyperglycemia via upregulation of AMP kinase and downregulation of NFkappaB. Similar findings were observed in rat primary hepatocytes.
  
  
  CONCLUSIONS
  Thus, in obesity and diabetes, the hypoadiponectinemia could exacerbate the proinflammatory state by inducing CRP production.
authors.affiliation: Laboratory for Atherosclerosis and Metabolic Research, 4635 Second Avenue, Sacramento, CA 95817, USA.
authors.forename: Sridevi
authors.initials: S
authors.lastname: Devaraj
authors.forename: Natalie
authors.initials: N
authors.lastname: Torok
authors.forename: Mohan R
authors.initials: MR
authors.lastname: Dasu
authors.forename: David
authors.initials: D
authors.lastname: Samols
authors.forename: Ishwarlal
authors.initials: I
authors.lastname: Jialal
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D042783:Endothelial Cells / Q000201:enzymology / Q000378:metabolism*; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D050791:STAT Transcription Factors / Q000378:metabolism; D014162:Transfection
chemical_list: D052242:Adiponectin; D022782:CCAAT-Enhancer-Binding Protein-beta; D020672:I-kappa B Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D050791:STAT Transcription Factors; D002097:C-Reactive Protein; D020928:Mitogen-Activated Protein Kinases; D000263:Adenylate Kinase; D005947:Glucose