TY - JOUR
T1 - Functional Metabolomics Reveals that Astragalus Polysaccharides Improve Lipids Metabolism through Microbial Metabolite 2-Hydroxybutyric Acid in Obese Mice
AU - Li, Bingbing
AU - Hong, Ying
AU - Gu, Yu
AU - Ye, Shengjie
AU - Hu, Kaili
AU - Yao, Jian
AU - Ding, Kan
AU - Zhao, Aihua
AU - Jia, Wei
AU - Li, Houkai
N1 - Funding Information:
This work was funded by the National Natural Science Foundation of China (81673662 and 81873059) and the Program for Professor of Special Appointment (Eastern Scholar) & Shuguang Scholar (16SG36) at the Shanghai Institutions of Higher Learning from Shanghai Municipal Education.
Publisher Copyright:
© 2021 THE AUTHORS. Published by Elsevier LTD on behalf of Chinese Academy of Engineering and Higher Education Press Limited Company.
PY - 2022/2
Y1 - 2022/2
N2 - Polysaccharides are widely present in herbs with multiple activities, especially immunity regulation and metabolic benefits for metabolic disorders. However, the underlying mechanisms are not well understood. Functional metabolomics is increasingly used to investigate systemic effects on the host by identifying metabolites with particular functions. This study explores the mechanisms underlying the metabolic benefits of Astragalus polysaccharides (APS) by adopting a functional metabolomics strategy. The effects of APS were determined in eight-week high-fat diet (HFD)-fed obese mice. Then, gas chromatography–time-of-flight mass spectrometry (GC–TOFMS)-based untargeted metabolomics was performed for an analysis of serum and liver tissues, and liquid chromatography–tandem mass spectrometry (LC–MS/MS)-based targeted metabolomics was performed. The potential functions of the metabolites were tested with in vitro and in vivo models of metabolic disorders. Our results first confirmed the metabolic benefits of APS in obese mice. Then, metabolomics analysis revealed that APS supplementation reversed the HFD-induced metabolic changes, and identified 2-hydroxybutyric acid (2-HB) as a potential functional metabolite for APS activity that was significantly decreased by a HFD and reversed by APS. Further study indicated that 2-HB inhibited oleic acid (OA)-induced triglyceride (TG) accumulation. It was also found to stimulate the expression of proteins in lipid degradation in hepatocytes and TG lipolysis in 3T3-L1 cells. Moreover, it was found to reduce serum TG and regulate the proteins involved in lipid degradation in high-fat and high-sucrose (HFHS)-fed mice. In conclusion, our study demonstrates that the metabolic benefits of APS are at least partially due to 2-HB generation, which modulated lipid metabolism both in vitro and in vivo. Our results also highlight that functional metabolomics is practical for investigating the mechanism underlying the systemic benefits of plant polysaccharides.
AB - Polysaccharides are widely present in herbs with multiple activities, especially immunity regulation and metabolic benefits for metabolic disorders. However, the underlying mechanisms are not well understood. Functional metabolomics is increasingly used to investigate systemic effects on the host by identifying metabolites with particular functions. This study explores the mechanisms underlying the metabolic benefits of Astragalus polysaccharides (APS) by adopting a functional metabolomics strategy. The effects of APS were determined in eight-week high-fat diet (HFD)-fed obese mice. Then, gas chromatography–time-of-flight mass spectrometry (GC–TOFMS)-based untargeted metabolomics was performed for an analysis of serum and liver tissues, and liquid chromatography–tandem mass spectrometry (LC–MS/MS)-based targeted metabolomics was performed. The potential functions of the metabolites were tested with in vitro and in vivo models of metabolic disorders. Our results first confirmed the metabolic benefits of APS in obese mice. Then, metabolomics analysis revealed that APS supplementation reversed the HFD-induced metabolic changes, and identified 2-hydroxybutyric acid (2-HB) as a potential functional metabolite for APS activity that was significantly decreased by a HFD and reversed by APS. Further study indicated that 2-HB inhibited oleic acid (OA)-induced triglyceride (TG) accumulation. It was also found to stimulate the expression of proteins in lipid degradation in hepatocytes and TG lipolysis in 3T3-L1 cells. Moreover, it was found to reduce serum TG and regulate the proteins involved in lipid degradation in high-fat and high-sucrose (HFHS)-fed mice. In conclusion, our study demonstrates that the metabolic benefits of APS are at least partially due to 2-HB generation, which modulated lipid metabolism both in vitro and in vivo. Our results also highlight that functional metabolomics is practical for investigating the mechanism underlying the systemic benefits of plant polysaccharides.
KW - 2-Hydroxybutyric acid
KW - Astragalus polysaccharides (APS)
KW - Functional metabolomics
KW - Obesity
UR - http://www.scopus.com/inward/record.url?scp=85099606177&partnerID=8YFLogxK
U2 - 10.1016/j.eng.2020.05.023
DO - 10.1016/j.eng.2020.05.023
M3 - Journal article
AN - SCOPUS:85099606177
SN - 2095-8099
VL - 9
SP - 111
EP - 122
JO - Engineering
JF - Engineering
ER -
