5% saturated fat) or an appropriate control diet (CD, 5.4% fat). Mice on HFD additionally received drinking water enriched with fructose and glucose. Analyses including biomet-ric, serological, histological, Western Blot and RT-PCR testing were performed after a dietary period of 12 weeks. Results: 12 weeks of HFD feeding induced a significant selleck chemicals weight gain, which was more pronounced in Bcl-3hepar mice. Moreover HFD caused elevated levels of serum ALT, triglycerides,
total cholesterol, serum fasting glucose and insulin in parallel to an increase in the relative liver weight and hepatic steatosis on H&E stain. In Bcl-3hepar mice ALT and insulin levels were significantly higher compared to the wt. In parallel, the insulin-receptor, IRS-3 and −4 in hepatic tissue were downregulated in Bcl-3hepar mice, whereas levels of IRS-1 and −2 were comparable in both genotypes. Phosphorylation of the serine-threonine kinase Akt was unaffected. Next, key regulators of hepatic glu-coneogenesis Obeticholic Acid ic50 and lipogenesis were examined. We detected a significant down-regulation of the phosphoenolpyruvate carboxykinase (PEPCK), the fructose-1,6-bisphosphatase gene Fbp-1 and Glucose-6 phosphatase (G6P) in Bcl-3hepar mice on HFD compared to the wt. In parallel, expression of regulators of hepatic de novo fatty acid synthesis including ACC, FAS and SREBP-1 were upregulated, whereas the expression of CPT1, PPARalpha and its
regulator PGC-1alpha – all of which restrict MCE公司 hepatic beta-oxidation – were downregulated in Bcl-3hepar mice. Conclusion: The regulator of cellular survival and hepatic inflammation Bcl-3 directly influences the metabolic and injurious phenotype observed in NAFLD and
thus could be an important target in the development of novel therapies. Disclosures: Peter R. Galle – Advisory Committees or Review Panels: Bayer, BMS, Lilly, Daiichi, Jennerex; Consulting: Medimmune; Grant/Research Support: Roche, Lilly; Speaking and Teaching: Bayer, BMS Marcus A. Woerns – Advisory Committees or Review Panels: Bayer, Bayer The following people have nothing to disclose: Nadine Gehrke, Amrit Mann, Yvonne Alt, Arno Schad, Ari Waisman, Jorn M. Schattenberg Background and Aim: Nonalcoholic fatty liver disease (NAFLD) has become one of the most common liver diseases worldwide. However, the factor which promotes progression of NAFLD remains unclear. S100A8, an endogenous Toll-like receptor 4 agonist released from myeloid lineage cells, has been attracting attention because it can play a pivotal role in inflammatory diseases. The aim of this study is to investigate the involvement of S100A8 in the progression of NAFLD. Method: We utilized a lithogenic diet (LD) model of NAFLD. Six-week-old male C57/ BL6 mice were fed with the LD or normal diet (ND) for 3 weeks. We also analyzed liver tissues from the patients with NAFLD. Results: We performed S100A8 Immunohistochemical staining of liver tissues from the NAFLD patients (n=54).
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