Up-regulation of the anti-inflammatory adipokine adiponectin in acute liver failure in mice

• Published in: Journal of hepatology 2006-03, Vol.44 (3), p.537-543
• Main Authors: Wolf, Anna Maria, Wolf, Dominik, Avila, Matias A., Moschen, Alexander R., Berasain, Carmen, Enrich, Barbara, Rumpold, Holger, Tilg, Herbert
• Format: Article
• Language: English
• Subjects: Acute liver failure; Adiponectin; Adiponectin - genetics; Adiponectin - metabolism; Animals; Biological and medical sciences; ConA; Concanavalin A - toxicity; Cytokines; Disease Models, Animal; Endothelial Cells - metabolism; Female; Gastroenterology. Liver. Pancreas. Abdomen; Hepatocytes - metabolism; Hepatocytes - pathology; Inflammation; Interleukin-10 - genetics; Interleukin-10 - metabolism; Liver Failure, Acute - genetics; Liver Failure, Acute - metabolism; Liver Failure, Acute - pathology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Macrophages - metabolism; Macrophages - pathology; Medical sciences; Mice; Mice, Inbred BALB C; Other diseases. Semiology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Up-Regulation
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2005.08.019

Recent reports suggest that the adipose tissue and adipokines are potent modulators of inflammation. However, there is only scarce knowledge on the functional role and regulation of endogenous adiponectin in non-fat tissues such as the liver under conditions of acute inflammation. In the present study, we investigated adiponectin expression in healthy murine liver tissue and under inflammatory conditions in vivo. Adiponectin mRNA was readily detectable in healthy liver tissue and further increased in ConA-mediated acute liver failure. Adiponectin protein expression was mainly found in hepatic endothelial cells. In vitro adiponectin mRNA expression was detectable in several cell types, including primary hepatic sinusoidal endothelial cells, stellate cells, and macrophages. Mice pretreated with adiponectin before ConA administration developed reduced hepatic injury as shown by decreased release of transaminases and reduced hepatocellular apoptotis. Of note, TNF-α levels were not affected by adiponectin, whereas IL-10 production was increased. Neutralisation of IL-10 diminished the protective effect of adiponectin. Adiponectin expression is up-regulated in ConA-mediated acute liver failure. Therefore, adiponectin might play a role in the control and limitation of inflammation in the liver. Moreover, our data suggest a role for IL-10 in adiponectin-mediated hepatoprotection.