On the other hand, animals in Lt/HF group decreased energy expenditure with lost BAT compensations and developed more severe lipid and glucose intolerance, hepatic steatosis, inflammation and hepatocyte ballooning. Contrary to our expectations, cBATX caused a further recruitment of iBAT both in St/C and St/HF groups, which could compensate energy expenditure loss by excised tissue, but not in Lt/HF group. Ad-MSCs population in St/HF group was higher (Sca-1: >95%, CD29: >99%, CD44: >60%, CD105: >40%) with abundant differentiation capacity to WAT and iBAT than that in Lt/HF group. Interestingly,

Ad-MSCs Tx significantly improved body weight gain, energy expenditure loss and findings of NAFLD with the appearance of donor cell derived iBAT in Lt/HF group. Conclusion: Impaired metabolic compensation in adipose tissues resulted in progression of NAFLD, which selleckchem was based on deteriorated Ad-MSCs capacity. New approach targeted this pathway as cell transplantation could be a potent strategy for preventing NAFLD. Disclosures: Kohichiroh Yasui – Grant/Research Support: AstraZeneca K.K., CHUGAI Pharmaceutical Co., Ltd., Dainippon Sumitomo Pharma Co., Ltd., Eisai Co., Ltd., FUJIFILM Medical Co., Ltd., Merck Serono, MSD K.K., Otsuka Pharmaceutical Co., Ltd. Yoshito Itoh – Grant/Research Support: MSD KK, Bristol-Meyers

Squibb, Dain-ippon Sumitomo Pharm. Co., Ltd., Otsuka Pharmaceutical Co., Chugai Pharm Co., Ltd, Mitsubish iTanabe Pharm. Co.,Ltd., SAHA HDAC clinical trial Daiichi Sankyo Pharm. Co.,Ltd., Takeda Pharm. Co.,Ltd., AstraZeneca K.K.:, Eisai

Co.,Pharm.Ltd, FUJIFILM Medical Co.,Ltd. The following people have nothing to disclose: Taichiro Nishikawa, Hisakazu Nakajima, Satoru Sugimoto, Ikuyo Itoh, Kazuki Koudou, Tomoki Nakajima, Kanji Yamaguchi, Michihisa Moriguchi, Yoshio Sumida, Hironori Mitsuyoshi, Masahito Minami The pathogenesis of liver injury and inflammation Etofibrate in nonalcoholic steatohepatitis (NASH) is obscure. We have previously reported that toxic free fatty acids induce hepatocyte lipoapoptosis in vitro by activating the TRAIL receptor (TR). The AIMS of this study were to examine the role of TR-mediated signaling in a murine model of NASH. METHODS: TR knockout (TR−/−) mice, mice with conditional deletion of caspase-8 in hepatocytes (Casp8Δhepa) and wild-type (WT) littermates were fed a diet high in saturated fat, cholesterol and fructose (FFC) or chow for 6 or 3 months, respectively. RESULTS: FFC-fed WT and TR−/− mice had comparable caloric intake and activity. However, the FFC-fed TR−/− mice had reduced liver triglyceride content, lower serum ALT values, and hepatocyte apoptosis by TUNEL assay as compared to WT mice. Moreover, TR−/− mice displayed attenuation of liver fibrosis by mRNA levels of collagen-1a and Sirius red staining.