title: AICAR stimulates adiponectin and inhibits cytokines in adipose tissue.
abstract: 5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR) can be used as an experimental tool to activate 5'-AMP-activated protein kinase (AMPK) and has been shown to improve insulin sensitivity. In parallel adiponectin also seems to activate AMPK and to improve insulin sensitivity. We have investigated the effects of AICAR on the gene expression of adiponectin and on gene expression and release of cytokines in human adipose tissue in vitro. AICAR stimulated AMPK alpha1 activity 3-4-fold (p<0.001), and dose-dependently increased adiponectin mRNA levels with significant stimulation (2-4-fold) at AICAR concentrations of 0.5-2mM (p<0.05). The adipose tissue protein release of tumor necrosis factor-alpha (TNF- alpha) and interleukin-6 (IL-6) was decreased by AICAR (p<0.05). In conclusion, AICAR stimulated adipose tissue AMPK alpha1 activity and adiponectin gene expression, while attenuating the release of TNF-alpha and IL-6. Reduced concentrations of these cytokines and increased levels of adiponectin might play a role for the insulin sensitizing effects of AICAR.
authors.affiliation: Department of Endocrinology and Metabolism, Aarhus University Hospital, Tage Hansensgade 2, Aarhus Sygehus, DK-8000 Aarhus C, Denmark. lihn@dadlnet.dk
authors.forename: Aina S
authors.initials: AS
authors.lastname: Lihn
authors.forename: Niels
authors.initials: N
authors.lastname: Jessen
authors.forename: Steen B
authors.initials: SB
authors.lastname: Pedersen
authors.forename: Sten
authors.initials: S
authors.lastname: Lund
authors.forename: Bjørn
authors.initials: B
authors.lastname: Richelsen
mesh_terms: D055372:AMP-Activated Protein Kinases; D052242:Adiponectin; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012265:Ribonucleotides / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D052242:Adiponectin; D016207:Cytokines; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D009097:Multienzyme Complexes; D020033:Protein Isoforms; D011506:Proteins; D012333:RNA, Messenger; D012265:Ribonucleotides; D014409:Tumor Necrosis Factor-alpha; D000620:Aminoimidazole Carboxamide; D012313:RNA; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human; C031143:AICA ribonucleotide