Abstract: Objective To detect the pathological changes in obese mice liver and explore the effects of obesity on hepatic metabolism. Methods Obese mouse model was successfully constructed by consecutive 24 weeks of high fat diet (HFD), while control group was fed with a standard chow diet (CD). After 24 weeks, mice liver was dissected, and the pathological characteristics of liver were observed with hematoxylin-eosin (HE) staining and Sirius red staining. The metabolome of liver was detected by ultra-high performance liquid chromatography-mass spectrometry(UPLC-MS) after extraction by 80% methanol. Principal component analysis (PCA), differential metabolite analysis and KEGG pathway enrichment analysis were performed to find the metabolic changes in the liver of obese mice. Results After 24 weeks of high fat diet, the body weight and liver weight of HFD group mice were much higher than that of CD group mice. Besides, HFD group mice liver showed severe steatosis and slight fibrosis. There were also significant differences in liver metabolites between HFD and CD groups, and the metabolic changes were mainly enriched in pathways of phenylalanine metabolism, citric acid cycle (TCA cycle), sphingolipid metabolism, arginine biosynthesis and primary bile acid biosynthesis. Conclusions The obese mouse model was successfully constructed, and the pathological characteristics of obese mice liver were elucidated. At the same time,the main metabolic pathway changes of obese mice liver were further revealed by metabonomics analysis.

Key words: obesity, liver, metabolome, diet induction