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129th General Meeting of Korean Chemical Society & Exposition Metabolomic analysis in liver tissues from mouse model to determine the role of AMPK activator in NASH using LC-MS

Submission Date :
2 / 17 / 2022 , 16 : 13 : 40
Abstract Number :
129021730337
Presenting Type:
Oral Presentation
Presenting Area :
Analytical Chemistry - Oral Presentation of Young Analytical Chemists II
Authors :
Yeajin Ju, Jueun Lee*, Geum-Sook Hwang*
Western Seoul Center, Korea Basic Science Institute, Korea
Assigned Code :
ANAL2.O-13 Assigend Code Guideline
Presenting Time :
FRI, 09 : 48
Non-alcoholic steatohepatitis (NASH) is a risk factor for hepatocellular carcinoma lead to liver cell damage and inflammation along with fatty deposition. AMP-activated protein kinase (AMPK) plays an important function in controlling energy homeostasis and the activation can inhibit NASH pathology. However, the effect of the AMPK activation on hepatic metabolic rewiring remains unknown. This study aimed to investigate the therapeutic effects of AMPK on hepatic metabolism on NASH using metabolic analysis. C57BL/6J male mice were fed a choline-deficient high fat diet (CD-HFD) for 6 weeks to induce NASH and treated them with YE-21, a new direct AMPK activator candidate, every 2 days for 14 times. Then, we performed metabolic profiling of liver tissue using ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry. Mice were divided into four groups: control (n=12), YE-21 (n=12), CD-HFD (n=12), and CD-HFD+YE-21 (n=12). We observed strong separation among three groups of control, CD-HFD and CD-HFD+YE-21 mice in partial least squares-discriminant analysis score plots. A total of 92 metabolites were identified in positive and negative mode. To find key metabolic pathways after YE-21 treatment in mice fed CD-HFD, pathway analysis was performed using significantly different 17 metabolites between CD-HFD and CD-HFD+YE-21. As a result, the most enriched metabolic pathways were cysteine and methionine metabolism, pyrimidine metabolism and amino sugar and nucleotide sugar metabolism. In particular, s-adenosyl homocysteine significantly increased in CD-HFD+YE-21 compared to CD-HFD, whereas cystathione and glutathione oxidized (GSSG) were significantly decreased in CD-HFD+YE-21 compared to CD-HFD in cysteine and methionine metabolism. Our finding suggested that YE-21 might improve liver damage and fibrosis due to NASH by regulating hepatic metabolism, and demonstrated that metabolic profiling is a useful method to investigate the therapeutic effects of AMPK activation in diet-induced NASH mice.