1273 OBESITY-INDUCED NAFLD: IDENTIFICATION OF TRANSCRIPTIONAL MASTER REGULATORS CONTROLLING METABOLIC AND INFLAMMATORY RESPONSES TO HIGH FAT DIET IN LIVER AND ADIPOSE TISSUE

Material and Methods: C57BL/6 mice, fed a high-fat diet (HFD) for 24 weeks, were confirmed to result in NASH, and devided into four groups for additional 24 weeks treatment. HFD group was fed HFD for 48 weeks, UDCA group was fed with HFD for 24 weeks, and then HFD+UDCA at a dose of 20mg/(kg.d) via gavages for additional 24 weeks, PUFA group was fed with HFD for 24 weeks, and then HFD+PUFA at a dose of 70mg/(kg.d) via gavages for following 24 weeks, and UDCA+PUFA group was fed with HFD for 24 wk, followed by HFD+UDCA+PUFA for 24 weeks. At the end of the experiment, body weight, serum biochemical index, and hepatopathologic changes by CRN scoring system were examined. Results: Liver showed hypertrophic and yellowish color change and all mice developed steatohepatitis after 24-week-HFD. The mean CRN scores by their liver histology as follows: 2.9±0.3 in steatosis, 2.65±0.7 in lobular inflammation, 1.8±0.4 in ballooning and 1.9±0.3 in fibrosis. After additional 24 weeks of HFD, only fibrosis score was increased significantly to 2.4±0.3. Treatment with UDCA and/or PUFA reduced liver/body weight ratio. Compared with the HFD group, significant improvement of steatosis was noted only in the UDCA group. Lobular inflammation was improved significantly both in UDCA and UDCA+PUFA groups compared with the HFD group. However, significant improvement of fibrosis was seen only in the UDCA+PUFA group. Conclusion: UDCA might play a role in the improvement of steatosis and lobular inflammation. Co-treatment of UDCA and PUFA reduces inflammation and finally fibrosis. For clinical application for NASH, UDCA and PUFA co-administration can be beneficial to prevent progression into cirrhosis.