title: Adiponectin induces the transforming growth factor decoy receptor BAMBI in human hepatocytes.
abstract: Transforming growth factor (TGF) β is the central cytokine in fibrotic liver diseases. We analyzed whether hepatoprotective adiponectin directly interferes with TGFβ1 signaling in primary human hepatocytes (PHH). Adiponectin induces the TGFβ decoy receptor BMP-and activin-membrane-bound inhibitor (BAMBI) in PHH. Overexpression of BAMBI in hepatoma cells impairs TGFβ-mediated phosphorylation of SMAD2 and induction of connective tissue growth factor. BAMBI is lower in human fatty liver with a higher susceptibility to liver fibrosis and negatively correlates with BMI of the donors. Hepatic BAMBI is reduced in rodent models of liver inflammation and fibrosis. In summary, the current data show that hepatoprotective effects of adiponectin include induction of BAMBI which is reduced in human fatty liver and rodent models of metabolic liver injury.
authors.affiliation: Department of Internal Medicine I, University Hospital of Regensburg, Regensburg, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Wanninger
authors.forename: Markus
authors.initials: M
authors.lastname: Neumeier
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bauer
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Weiss
authors.forename: Kristina
authors.initials: K
authors.lastname: Eisinger
authors.forename: Roland
authors.initials: R
authors.lastname: Walter
authors.forename: Christoph
authors.initials: C
authors.lastname: Dorn
authors.forename: Claus
authors.initials: C
authors.lastname: Hellerbrand
authors.forename: Andreas
authors.initials: A
authors.lastname: Schäffler
authors.forename: Christa
authors.initials: C
authors.lastname: Buechler
mesh_terms: D052242:Adiponectin / Q000494:pharmacology*; D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000633:toxicity; D004041:Dietary Fats / Q000008:administration & dosage / Q000633:toxicity; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D005260:Female; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051899:Smad2 Protein / Q000378:metabolism*
chemical_list: D052242:Adiponectin; C485671:BAMBI protein, human; D002791:Cholesterol, Dietary; D004041:Dietary Fats; D008565:Membrane Proteins; D051899:Smad2 Protein