Adiponectin and its receptors in rodent models of fatty liver disease and liver cirrhosis.
OBJECTIVE
To determine circulating and hepatic adiponectin in rodents with fatty liver disease or liver cirrhosis and investigate expression of the adiponectin receptors AdipoR1 on the mRNA and protein level and AdipoR2 on the mRNA level.


METHODS
Fat fed rats were used as a model for fatty liver disease and bile duct ligation in mice to investigate cirrhotic liver. Expression of AdipoR1 and AdipoR2 mRNA was determined by real time RT-PCR. AdipoR1 protein was analysed by immunoblot. Adiponectin was measured by ELISA.


RESULTS
Systemic adiponectin is reduced in fat-fed rats but is elevated in mice after bile duct ligation (BDL). Hepatic adiponectin protein is lower in steatotic liver but not in the liver of BDL-mice when compared to controls. Adiponectin mRNA was not detected in human liver samples or primary human hepatocytes nor in rat liver but recombinant adiponectin is taken up by isolated hepatocytes in-vitro. AdipoR1 mRNA and AdipoR1 protein levels are similar in the liver tissue of control and fat fed animals whereas AdipoR2 mRNA is induced. AdipoR2 mRNA and AdipoR1 mRNA and protein is suppressed in the liver of BDL-mice.


CONCLUSIONS
Our studies show reduced circulating adiponectin in a rat model of fatty liver disease whereas circulating adiponectin is elevated in a mouse model of cirrhosis and similar findings have been described in humans. Diminished hepatic expression of adiponectin receptors was only found in liver cirrhosis.
Neumeier
Markus
M
Department of Internal Medicine I, University of Regensburg, Regensburg D-93042, Germany. christa.buechler@klinik.uni-regensburg.de
Hellerbrand
Claus
C
Gäbele
Erwin
E
Buettner
Roland
R
Bollheimer
Cornelius
C
Weigert
Johanna
J
Schäffler
Andreas
A
Weiss
Thomas S
TS
Lichtenauer
Monika
M
Schölmerich
Jurgen
J
Buechler
Christa
C
D052242:Adiponectin / Q000097:blood* / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000097:blood* / Q000235:genetics; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000097:blood* / Q000235:genetics / Q000378:metabolism
C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; C475419:adiponectin receptor 1, mouse; C504339:adiponectin receptor 1, rat; C475421:adiponectin receptor 2, mouse; C506573:adiponectin receptor 2, rat