title: Adiponectin protects LPS-induced liver injury through modulation of TNF-alpha in KK-Ay obese mice.
abstract: Adiponectin, an adipocytokine, has been identified in adipose tissue, and its receptors are widely distributed in many tissues, including the liver. The present study was performed to clarify the role of adiponectin in lipopolysaccharide (LPS)-induced liver injury using KK-Ay obese mice. We analyzed the effects of adiponectin pretreatment on liver injury induced by D-galactosamine/LPS (GalN/LPS) in KK-Ay obese mice. GalN/LPS treatment induced significant increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in the blood, apoptotic and necrotic changes in hepatocytes, and/or showed a high degree of lethality. The GalN/LPS-induced liver injury was more pronounced in KK-Ay obese mice than in lean controls. Pretreatment with adiponectin ameliorated the GalN/LPS-induced elevation of serum AST and ALT levels and the apoptotic and necrotic changes in hepatocytes, resulting in a reduction in lethality. In addition, pretreatment with adiponectin attenuated the GalN/LPS-induced increases in serum and hepatic tumor necrosis factor alpha (TNF-alpha) levels and increased peroxisome proliferator-activated receptor (PPAR) alpha messenger RNA expression in the liver. Furthermore, abdominal macrophages from KK-Ay obese mice pretreated with adiponectin in vitro exhibited decreased LPS-induced TNF-alpha production compared with controls. Finally, adiponectin pretreatment also ameliorated TNF-alpha-induced liver injury. In conclusion, these findings suggest that adiponectin prevents LPS-induced hepatic injury by inhibiting the synthesis and/or release of TNF-alpha of KK-Ay obese mice.
authors.affiliation: Department of Internal Medicine, School of Medicine, Oita University, Hasama, Oita, Japan. MASAKI@med.oita-u.ac.jp
authors.forename: Takayuki
authors.initials: T
authors.lastname: Masaki
authors.forename: Seiichi
authors.initials: S
authors.lastname: Chiba
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tatsukawa
authors.forename: Tohru
authors.initials: T
authors.lastname: Yasuda
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Noguchi
authors.forename: Masataka
authors.initials: M
authors.lastname: Seike
authors.forename: Hironobu
authors.initials: H
authors.lastname: Yoshimatsu
mesh_terms: D052242:Adiponectin; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury; D019610:Cytoprotection; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008107:Liver Diseases / Q000401:mortality / Q000503:physiopathology / Q000517:prevention & control*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009336:Necrosis; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009994:Osmolar Concentration; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase