Molecular Mechanism Of Interventions In Treating NAFLD Mice With Xyloketal B

OBJIECTIVE: A NAFLD mouse model was established by feeding with foodcontaining high fat and high fructose. Then we treated those mice with Xyloketal B toexplore its curative effect for NAFLD. Combinating the pathogeny of NAFLDinduced by high fat and high fructose diet，we aim to explore the mechanisms ofXyloketal B treating NAFLD and regulating lipid metabolism on molecular levels.And we wish to provide treatment basis for the diseases causing by lipid metabolismimbalance.METHODS: Mice were fed with high fat and high fructose food for4weeks, thenwe detected the blood lipid and fasting blood-glucose and observed the liver biopsy toestimate the NAFLD mouse model. After peritoneal injection of Xyloketal B withdiffrent concentration (40,20,10mg/kg/d) and atorvastatin (15mg/kg/d)40days, theblood lipid, fasting blood-glucose, liver TG, liver Oxidative Stress level were detected.Meanwhile, the liver biopsy was observed to assess the effect of Xyloketal B forNAFLD mice model. To explore the mechanism, Real-time quantitative PCR andWestern blotting were used to detect the mRNA and protein expression of the enzymecorrelated with liver fatty acid metabolism.RESULTS: After feeding with high fat and high fructose food for4weeks, themouse liver Steatosis formed. Blood Lipid (TG, TC, HDL-C) and fastingblood-glucose regulated down significantly after treating with Xyloketal B for40days. and the liver biopsy showed that the liver of model group accompanied with alarge fat cavitation and localized inflammation. While the treatment groups withXyloketal B or atorvastatin ameliorated significantly. The high concentration groupand middle concentration group basically returned to normal and the lowconcentration group and atorvastatin group accompanied with a few fat cavitation and localized inflammation. And compaired with Model group, The liver TG of alltreatment groups were decreased, and liver Oxidative Stress ameliorated. The keyenzymes associated with liver fatty synthesis including PEPCK、ACL、ACC1、FAS、SCD-1, were down-regulated, and CPT1, the key enzyme for beta-oxidation, wasup-regulated significantly.CONCLUSION: Xyloketal B could decrease the blood lipid, fasting blood-glucoseand liver TG. The molecular detected resaults showed that Xyloketal B ameliorateNAFLD by down-regulating FAS, ACC1, SCD-1and up-regulating CPT1, PEPCK todecrease liver fatty acid synthesis and enhance beta-oxidation, meanwhile,ameliorating liver Oxidative Stress to decrease inflammation.