PMID- 19481767 OWN - NLM STAT- MEDLINE DCOM- 20100603 LR - 20181201 IS - 1095-8673 (Electronic) IS - 0022-4804 (Linking) VI - 161 IP - 2 DP - 2010 Jun 15 TI - Adiponectin deficiency promotes the production of inflammatory mediators while severely exacerbating hepatic injury in mice with polymicrobial sepsis. PG - 301-11 LID - 10.1016/j.jss.2008.12.021 [doi] AB - 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. MATERIALS AND 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. CONCLUSION: These results suggest that an APN deficiency induces an excessive systemic inflammatory status and exacerbates hepatic injury during polymicrobial sepsis. CI - Copyright 2010 Elsevier Inc. All rights reserved. FAU - Uji, Yoshitaka AU - Uji Y AD - Department of Surgery, Shiga University of Medical Science, Shiga, Japan. FAU - Yamamoto, Hiroshi AU - Yamamoto H FAU - Maeda, Kazuhisa AU - Maeda K FAU - Tsuchihashi, Hiroshi AU - Tsuchihashi H FAU - Akabori, Hiroya AU - Akabori H FAU - Shimizu, Tomoharu AU - Shimizu T FAU - Endo, Yoshihiro AU - Endo Y FAU - Shimomura, Iichiro AU - Shimomura I FAU - Tani, Tohru AU - Tani T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090114 PL - United States TA - J Surg Res JT - The Journal of surgical research JID - 0376340 RN - 0 (Adiponectin) RN - 0 (Fibrinolytic Agents) RN - 0 (Inflammation Mediators) RN - 0 (Interleukin-6) RN - 0 (Receptors, CCR2) RN - 0 (Thiazolidinediones) RN - 0 (Tumor Necrosis Factor-alpha) RN - 05V02F2KDG (Rosiglitazone) RN - EC 2.6.1.2 (Alanine Transaminase) SB - IM MH - Adiponectin/*deficiency MH - Alanine Transaminase/blood/metabolism MH - Animals MH - Disease Models, Animal MH - Fibrinolytic Agents/therapeutic use MH - Inflammation/blood/physiopathology MH - Inflammation Mediators/*metabolism MH - Interleukin-6/blood MH - Liver/enzymology/injuries/*pathology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Microscopy, Confocal MH - Punctures MH - Receptors, CCR2/blood MH - Rosiglitazone MH - Sepsis/*etiology/microbiology/physiopathology MH - Shock, Septic/*etiology/microbiology MH - Thiazolidinediones/*therapeutic use MH - Tumor Necrosis Factor-alpha/blood EDAT- 2009/06/02 09:00 MHDA- 2010/06/04 06:00 CRDT- 2009/06/02 09:00 PHST- 2008/10/21 00:00 [received] PHST- 2008/12/12 00:00 [revised] PHST- 2008/12/15 00:00 [accepted] PHST- 2009/06/02 09:00 [entrez] PHST- 2009/06/02 09:00 [pubmed] PHST- 2010/06/04 06:00 [medline] AID - S0022-4804(08)01580-1 [pii] AID - 10.1016/j.jss.2008.12.021 [doi] PST - ppublish SO - J Surg Res. 2010 Jun 15;161(2):301-11. doi: 10.1016/j.jss.2008.12.021. Epub 2009 Jan 14.