title: Adiponectin deficiency promotes the production of inflammatory mediators while severely exacerbating hepatic injury in mice with polymicrobial sepsis.
abstract: BACKGROUND
  Adiponectin (APN), which is an adipose tissue-derived hormone, is known as an anti-inflammatory cytokine. The effects of APN on the production of inflammatory mediators and hepatic injury during polymicrobial sepsis were evaluated using APN-knockout (KO) mice that had undergone a cecal ligation and puncture (CLP) and rosiglitazone, a selective peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, which increases the plasma APN concentration.
  
  
  METHODS
  Wild type (WT) and APN-KO mice were underwent CLP. The plasma and hepatic levels of inflammatory mediators, including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1), were measured before, at 24, and 48 h after CLP. A histological analysis of the liver and the plasma alanine aminotransferase (ALT) levels were examined to evaluate hepatic injury. The plasma levels of inflammatory mediators after CLP with pretreatment of rosiglitazone were compared with those without rosiglitazone.
  
  
  RESULTS
  APN deficiency resulted in significant increases in the plasma levels of TNF-alpha, IL-6, and MCP-1 at 24 h after CLP. Hepatic MCP-1 and plasma AST levels in APN-KO mice were significantly higher than those in WT mice at 48 h after CLP. A steatosis change and MCP-1 expressions in hepatocytes were induced in APN-KO mice during sepsis. The administration of rosiglitazone significantly lowered the plasma levels of inflammatory mediators, including TNF-alpha, IL-6, and MCP-1, in WT mice but not in APN-KO mice during sepsis.
  
  
  CONCLUSIONS
  These results suggest that an APN deficiency induces an excessive systemic inflammatory status and exacerbates hepatic injury during polymicrobial sepsis.
authors.affiliation: Department of Surgery, Shiga University of Medical Science, Shiga, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Uji
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Maeda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsuchihashi
authors.forename: Hiroya
authors.initials: H
authors.lastname: Akabori
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Shimizu
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Endo
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
authors.forename: Tohru
authors.initials: T
authors.lastname: Tani
mesh_terms: D052242:Adiponectin / Q000172:deficiency*; D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D007249:Inflammation / Q000097:blood / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000201:enzymology / Q000293:injuries / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D011677:Punctures; D054390:Receptors, CCR2 / Q000097:blood; D000077154:Rosiglitazone; D018805:Sepsis / Q000209:etiology* / Q000382:microbiology / Q000503:physiopathology; D012772:Shock, Septic / Q000209:etiology* / Q000382:microbiology; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D052242:Adiponectin; D005343:Fibrinolytic Agents; D018836:Inflammation Mediators; D015850:Interleukin-6; D054390:Receptors, CCR2; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone; D000410:Alanine Transaminase