Exendin-4 treatment increased the production of ketone bodies in all the treatments in comparison to control. Fatty acids themselves also led to an increase in ketone bodies probably as a normal cellular response, which was further enhanced by exendin-4. The difference between exendin treated and untreated fat loaded cell was insignificant in the case of oleic acid. In contrast exendin treatment increased significantly ketone body formation in cells loaded with either palmitic or elaidic acid exposure . Oil red O staining of liver sections from animals fed normal chow, ALIOS diet and subsequently treated with liraglutide illustrated a marked PCI-32765 reduction in the lipid load in hepatocytes. Also, there was a clear reduction in hepatic steatosis in drug treated animals . We further investigated the liver lysates for markers of UPR by immunoblotting and immunohistochemistry. Immunoblotting revealed suppression of GRP78 levels in animals fed ALIOS diet. Liraglutide injections in animals fed ALIOS diet reversed this effect by increasing GRP78 . Livers from animals administered the ALIOS diet demonstrated significant increases in CHOP protein in comparison to those given normal chow. In contrast, liraglutide treated mice had a remarkable reduction in CHOP protein levels . Densitometric analysis of the immunoblots confirmed these observations . In order to confirm if this difference in protein quantities was due to a transcriptional or post-transcriptional event, RTqPCR analysis was carried out for these two genes. Results revealed that liraglutide treatment enhanced GRP78 and suppressed CHOP expression . We extended these studies by visualizing GRP78 and CHOP protein levels in liver sections by immunohistochemistry. Differences in the amount of signal for GRP78 and CHOP were similar to those observed by immunoblotting .