1610-P: Oxymatrine Regulates Lipid Metabolism and Improves Oxidative Stress to Alleviate Nonalcoholic Fatty Liver Disease via PPARα-ApoA1/CPT1A Pathway—Combining Transcriptomics and Metabolomics

Introduction and Objective: Nonalcoholic fatty liver disease is the most common cause of chronic liver disease worldwide. Oxymatrine is a potent monomeric alkaloid extracted from the root of Sophora flavescens. This study aimed to explore the molecular mechanism of the improvement of oxymatrine on the liver of rats with nonalcoholic fatty liver disease induced by a high-fat and high-fructose diet by integrating transcriptomics and metabolomics. Methods: Wistar rats were fed a high-fat, high-fructose diet for 8 weeks and then gavaged with oxymatrine for the last 4 weeks. Biochemical indices and pathological changes of rats in each group were detected, and transcriptomics and metabolomics methods were used to analyze the changes in gene expression and metabolites in the liver and serum of rats, respectively. Results: Oxymatrine significantly reduced liver lipid accumulation and improved oxidative stress. Four differentially expressed genes, namely Apoa1, Cpt1a, Apob and Fga, were screened and identified through liver transcriptomics, revealing that oxymatrine inhibits lipid accumulation mainly by activating the PPARα-Cpt1a/Apoa1 pathway. In addition, metabolomic analysis showed that differential metabolites were mainly concentrated in glucagon signaling pathway, regulation of lipolysis in adipocytes, and signaling pathways related to lipid metabolism and oxidative stress, such as metabolism and sphingomyelin signaling pathways, and serum Ascorbic acid, Ergothioneine, s-methy GSH and other antioxidants were significantly up-regulated after oxymatrine intervention. Conclusion: Oxymatrine mainly inhibits lipid accumulation and improves oxidative stress by activating the PPARα-Apoa1/Cpt1a pathway, thereby improving non-alcoholic fatty liver disease. Disclosure L. Ren: None. X. Liu: None. F. Song: None. Y. Pan: None. J. Zhang: None. Funding Natural Science Foundation of Hebei Province (H2022307033)