Results: Compared to wild type mice, ASMase-/- mice were resistant to alcohol induced steatosis, exhibiting 70%ndash;90% lower trigliceride levels and oil red staining.

Consistent with these findings, alcohol-induced ER stress (Chop, Pdi) and liver injury (3%ndash;4 fold increase in ALT) were observed in wild type but not in ASMase null mice. Interestingly, increase PS-341 nmr in plasma Hcy levels was similar in wild type and ASMase null mice (5%ndash;7 fold). Wild type but not ASMase null mice exhibitied increased StARD1 overexpression and mitochondrial cholesterol trafficking by alcohol feeding. Moreover, evidence for Kupffer cell M1 /M2 polarization was similar for wild type and ASMase mice. Lysosomal permeabilization examined by NAG activation in the cytosol was lower in ASMase null mice compared to wild type

mice. Conclusion: ASMase null mice are resistant to intragastric alcohol-induced ER stress, steatosis, and liver injury despite severe Hcy, implying that the ability of Hcy to induce ER stress in response to alcohol is dependent on ASMase. Disclosures: Hidekazu Tsukamoto – Consulting: Shionogi & Co., S.P. Pharmaceutics; Grant/Research Support: The Toray Co. Neil Kaplowitz – Consulting: GlaxoSmithKline, RG7204 price JNJ, Merck, Novartis, Hepregen, Takeda, Otsuka; Independent Contractor: Acetaminophen Litigation The following people have nothing to disclose: Anna Baulies, Laura Martinez, Carmen Garcia-Ruiz, Jose Fernandez-Checa Backgrounds: The Wnt/β-catenin pathway is important for the regulation of liver growth, repair, and regeneration. It has been previously shown that chronic ethanol consumption blunts normal liver regenerative responses, in particular by inhibiting insulin/IGF signaling. Treatment with PPARδ agonist restored hepatic insulin responsiveness and normalized liver histology. Accordingly, we hypothesized whether these effects are associated with improvements in Wnt signaling. In this study, we investigated the effects

of chronic ethanol exposure selleck inhibitor and subsequent treatment with PPARδ agonist on the expression of Wnt pathway genes during a post-partial hepatectomy (PH) time course. Methods: Adult male Long Evans rats were fed with isocaloric liquid diets containing 0 or 37% ethanol for 8 weeks followed by 2/3 PH. During the last three weeks, a portion of rats was fed with PPARδ agonist. All animals were sacrificed at 0, 18, 24, 30, 48, 72 hour, and one week time points after PH. Total RNA was extracted from liver tissue. The expression of 19 genes involved in the Wnt pathway was quantified by reporter signal amplification using the Quantigene 2.0 Multiplex Assay (Affymetrix). Results: Chronic ethanol consumption led to expression changes in the 19 genes tested, demonstrating an inhibition of Wnt/β-catenin signaling.