1629-P: JTTZ Improves Glycolipid Metabolism Disorder by Regulating Liver Cell Fatty Acid Metabolism Reprogramming and ABCD2/PEX2/ATGL Pathway

Introduction and Objective: JTTZ, an empirical medicine, has a significant therapeutic effect on alleviating glucolipid metabolic disorders in clinical practice. However, its underlying mechanisms remain unclear. This study aims to elucidate the potential mechanisms of JTTZ in improving glucolipid metabolic disorders. Methods: Male C57BL/6J mice (6-8 weeks old) were fed a high-fat diet (HFD) for 8 weeks to establish a model of glucolipid metabolic disorder, followed by daily administration of JTTZ for 12 weeks. Metabolic status and hepatic steatosis were assessed through serum analysis and histological methods. Multi-omics approaches, RT-PCR, Western blot, immunohistochemistry, and flow cytometry were employed to investigate the regulatory effects of JTTZ on fatty acid metabolism and signaling pathways in both liver tissues of mice and oleic/palmitic acid-induced HepG2 cell models. Results: JTTZ significantly improved glucolipid metabolism and hepatic steatosis by reducing fasting blood glucose, lipid levels, and reactive oxygen species (ROS). It also decreased lipid droplet accumulation in both the liver and HepG2 cells. Multi-omics and validation studies revealed that JTTZ modulated the ABCD2/PEX2/ATGL pathway, promoting lipid droplet metabolism in hepatocytes and mitigating oxidative stress, thus contributing to metabolic reprogramming. Conclusion: JTTZ effectively ameliorates glucolipid metabolic disorders and fatty acid metabolism reprogramming, demonstrating potential therapeutic value. Its mechanism may involve the regulation of the ABCD2/PEX2/ATGL pathway. Disclosure R. Miao: None. Y. Zhang: None. X. Fang: None. Z. Yuxin: None. H. Shi: None. J. Tian: None. Funding National Natural Science Foundation of China (824743233); High Level Chinese Medical Hospital Promotion Project (HLCMHPP20230CZ40907); CACMS Outstanding Young Scientific and Technological Talents Program (ZZ13-YQ-026; Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences (CI2021A01601; Innovation Team Project of Science and Technology Innovation Engineering of China Academy of Chinese Medical Sciences(CI2021B008)