2. A group of potential fat metabolism related molecules and miRNAs, which were affected by SIRT1, were screened successfully. Key Word(s): 1. SIRT1; 2. lipid metabolism; 3. Microarray; 4. Screening; Presenting Author: XIAOLAN LU Additional Authors: JIN LI, HUIHUI MA, HAITAO SHI Corresponding Author: XIAOLAN LU Affiliations: Second Affiliate Hospital of Xian Jiao Tong University Objective: Some studies have reported that PPAR δ agonists play a role in regulating glucose metabolism, lipid metabolism and insulin resistance in type 2 diabetes, metabolic syndrome and coronary

atherosclerosis .However there is few report of the effect of PPAR δ agonists on NAFLD. The aim of this study is to investigate the effect and mechanism of SCH727965 concentration PPARδ agonist (GW501516) on non-alcoholic fatty liver disease induced by a high-fat diet in the rat. Methods: Male Sprague-Dawley (SD) rats were randomly divided into normal control group (n = 10), model group (n = 10), GW501516 treatment group (n = 12), pioglitazone

treatment group(n = 12). Drug treatments began when model was successfully established and the rats were sacrificed after treatment for 2 weeks and click here 4 weeks. Histopathological and biochemical analyses were carried. Fasting blood gucose and fasting insulin were detected and homeostasis model assessment (HOMA-IR) was calculate. ELISA was used to measure the serum IGF-1 level. Immunohistochemistry was used to detect protein expression of SREBP-1c and GLUT-2 in liver. Results: GW501516 significantly attenuated high-fat diet induced liver fat deposition. Serum

ALT and AST level, fasting blood glucose, fasting insulin and HOMA-IR were significantly lower in GW501516 group than in model group and pioglitazone medchemexpress group. Serum IGF-1 level and hepatic GLUT-2 expression was higher and hepatic SREBP-1c expression was lower in GW501516 group than in model group and pioglitazone group. After 4 weeks of treatment, there is no significant difference of HOMR-IA, serum IGF-1 level, hepatic GLUT-2 and SREBP-1c expression in GW501516 group and normal group. Conclusion: PPARδ agonist (GW501516) can improve insulin resistance and liver pathological change induced by high-fat diet. and the mechanism may be related to regulation of serum IGF-1 level, hepatic GLUT-2 and SREBP-1c expression. Key Word(s): 1. PPARδ agonist; 2. Insulin resistance; 3.