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


METHODS
In the present study, we investigated adiponectin expression in healthy murine liver tissue and under inflammatory conditions in vivo.


RESULTS
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-alpha levels were not affected by adiponectin, whereas IL-10 production was increased. Neutralisation of IL-10 diminished the protective effect of adiponectin.


CONCLUSIONS
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.
Wolf
Anna Maria
AM
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria.
Wolf
Dominik
D
Avila
Matias A
MA
Moschen
Alexander R
AR
Berasain
Carmen
C
Enrich
Barbara
B
Rumpold
Holger
H
Tilg
Herbert
H
D052242:Adiponectin / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D003208:Concanavalin A / Q000633:toxicity; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D017114:Liver Failure, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D052242:Adiponectin; D012333:RNA, Messenger; D003208:Concanavalin A; D016753:Interleukin-10