Also, hepato-cytes from Alb-Lpin1−/− mice had normal rates of triglyceride synthesis. In mice receiving high fat diet for 10 weeks, there was no difference between WT and Alb-Lpin1−/− in total body weight gain, plasma chemistries, glucose tolerance, or insulin signaling. Liver histology and the mRNA expression of markers of inflammation or stellate cell activation in the liver were also not different between genotypes. Conclusion: Collectively these data demonstrate that lipin 1 accounts for the inducible component of hepatic PAP activity, 3-deazaneplanocin A but that marked deficits in PAP activity do not impair hepatic triglyceride synthesis

nor does it affect insulin signaling or expression of markers of NASH in the liver in mice fed high fat diet. These data likely suggest that lipin 2-mediated PAP activity is more than sufficient for robust triglyceride

synthesis and development of fatty liver. Disclosures: The following people have nothing to disclose: Nisreen Soufi, George G. Schweitzer, Zhouji Chen, Connie Gan, Kyle McCommis, Brian Finck Background: Elevated circulating levels of free fatty acids are found in patients with Daporinad mouse metabolic syndrome is are associated with increased cell death and liver inflammation promoting the pathologic features of non-alcoholic fatty liver disease. Recently, we demonstrated that free fatty acids caused lipoapoptosis in cholangiocytes. Purpose: The purpose of this study was to test whether free fatty acids induced cholangio-cyte inflammatory cytokine production. Methods: Cultured human cholangiocyte and cholangiocarcinoma cell lines (H69, Mz-ChA-1, and KMCH) were used. The saturated free fatty acid palmitic acid was complexed with BSA and cells were treated for 2-24 hours. Cells were imaged by transmission electron microscopy. Cytokines were detected in the supernatant using a cytokine protein array while cytokine mRNA was quantified by RT-PCR. Inhibition of p38 mitogen activated protein kinase was achieved by treatment with SB203580. Results: Treatment of cultured cholangiocyte cell

lines with palmitic acid did not increase lipid droplet formation in PD184352 (CI-1040) cells but did cause a rapid increase in secreted IL-6, IL-8, and GM-CSF. This increase in secreted cytokine proteins was accompanied by an increase in mRNA for IL-6, IL-8, and GM-CSF. Additionally, TNF-α mRNA was also increased by palmitic acid treatment. A time course experiment of IL-6 and IL-8 mRNA in palmitic acid-treated cells showed rapid activation at 1-4 hours that returned to baseline by 8 hours. Activation of MAPKs occurred rapidly upon addition of palmitic acid so we tested the dependence of cytokine production on p38 activation. Cells pretreated with the p38 inhibitor SB203580 were protected against increased IL-6 and IL-8 production.