studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 689A
977
NorUDCA reduces liver injury and improves glucose
sensitivity in a mouse model of obesity and steatosis.
Daniel Steinacher 1 , Thierry Claudel 1 , Tatjana Stojakovic 2 , Michael
Trauner 1 ; 1 Gastroenterology and Hepatology, Medical University
of Vienna, Vienna, Austria; 2 Clinical Institute of Medical and
Chemical Laboratory Diagnostics, Medical University of Graz,
Graz, Austria
Background: Non-alcoholic fatty liver disease ranges from simple
benign steatosis to the more severe forms of non-alcoholic
steatohepatitis (NASH), cirrhosis and ultimately hepatocellular
carcinoma. Currently there is no satisfactory drug therapy
against NASH available. The leptin deficient mouse (ob/ob)
mimics metabolic syndrome and suffers from hyperinsulinemia,
insulin resistance, hyperlipidemia, hepatic steatosis and inflammation.
Bile acids (BA) are not only fat-absorption facilitators
but can also regulate metabolic processes directly. Currently,
ursodeoxycholic acid (UDCA) is the only BA used as a therapeutic
in humans, but has limited efficacy in NASH. NorUDCA
is a side-chained shortened derivative of UDCA improving liver
injury in mouse models of cholestatic liver and bile duct injury.
Therefore, we aimed to explore whether NorUDCA improves
liver damage and has beneficial metabolic effects in ob/ob
mice. Material & Methods: ob/ob mice received either a diet
supplemented with 0.5% NorUDCA or chow diet for 6 weeks.
Intraperitoneal glucose and insulin tolerance tests (IPGTT, IPITT)
were performed at week 5 and 6. Serum and urine biochemistry,
liver and fat histology were analyzed, gene and protein
expressions of key markers of inflammation, lipid and glucose
metabolism were assessed by RT-PCR and Western Blotting.
Results: Mice treated with NorUDCA showed a significant
reduction in AST, ALT and AP serum levels (p