Daily supplementation of cholecalciferol prevents liver steatosis and diabetes by improving insulin sensitivity in an animal model of NAFLD

s / Digestive and Liver Disease 47S (2015) e226–e235 e235 genetic inhibition of IDO-1 on the development of steatohepatitis induced by amethionine and choline-deficient (MCD) diet in mice. Methods: C57Bl/6 mice fed a MCD diet for 4 weeks, were treated with the specific IDO inhibitor, 1-methyl-d-triptophan (1MT, 5mg/ml) or its vehicle in drinking water. WT and IDO-1 KO C57Bl/6 mice were fed MCD or its vehicle for 4 weeks. Intrahepatic gene expression was assayed by quantitative real time PCR. Histological examination was assessed by formalin-fixed, paraffinembedded liver sections stainedwithhematoxylinandeosin (H&E). Results: No changes were observed in ALT levels in both pharmacological and genetic interference with IDO-1. Genetic deletion of IDO-1 resulted in an amelioration of the inflammatory phenotype. These effects were associated both with reduced intrahepatic gene expression of proinflammatory factors, including CD11b, CCL2, IL-1 beta and iNOS and with reduced necroinflammation score. Pharmacological inhibition of IDO by 1-MT administration did not affect the phenotype of dietary experimental steatohepatitis in terms of proinflammatory markers or inflammation score. Conclusions: Interference with IDO pathway by 1-MT administration did not affect the phenotype of dietary experimental steatohepatitis. On the other hand, genetic deletion of IDO-1 ameliorates liver injury induced by experimental steatohepatitis and modulates the expression of proinflammatory factors in this context. http://dx.doi.org/10.1016/j.dld.2015.07.044