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The effect of metformin on lipid disorders as measured by nuclear magnetic metabolomics and metabolic flux analysis
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Qi-feng LIU, Xue-qi Lü, Cong-cong GUO, Shan-shan SUN, Ya-nan WANG, Xiang-ju JIN, Ying-hong WANG*
Acta Pharmaceutica Sinica | 2021, 56(4) : 1109 - 1119
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Acta Pharmaceutica Sinica | 2021, 56(4): 1109-1119
Original Articles
The effect of metformin on lipid disorders as measured by nuclear magnetic metabolomics and metabolic flux analysis
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Qi-feng LIU, Xue-qi Lü, Cong-cong GUO, Shan-shan SUN, Ya-nan WANG, Xiang-ju JIN, Ying-hong WANG*
Affiliations
  • State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Published: 2021-04-12 doi: 10.16438/j.0513-4870.2020-1774
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Studies have found that metformin is not only the preferred drug for lowering blood sugar, but also shows lipid-lowering and weight-loss effects. The purpose of this study was to use a hyperlipidemia hamster model to investigate the lipid-lowering effect of metformin and its effect on important metabolic pathways in lipid metabolism disorders. Fifty golden hamsters were divided into a control group, a model group, metformin high- and low-dose groups, and a simvastatin group. A high-fat diet was fed for 1 week to create the model, and then drug was administered for 11 weeks with the high-fat diet. Serum was taken for measurement of blood lipid and blood glucose at 2, 6, and 9 weeks after administration, and at weeks 3, 5, and 9 feces and urine were collected for 1H NMR metabolomics tests. After 11 weeks of intravenous injection of[U-13C6] glucose, serum was collected for a 13C NMR metabolic flux test. The results showed that the administration of metformin can significantly reduce blood lipids and glucose levels and can significantly affect metabolic pathways such as sugar metabolism, lipid metabolism, ketone metabolism, amino acid metabolism, and intestinal flora metabolism. The results of the metabolic flux analysis showed that the high-fat diet reduced the metabolism of tricarboxylic acids by 37.48%. After administration of low and high doses of metformin the metabolism of tricarboxylic acid increased by 98.14% and 143.10%, respectively. After administration of simvastatin tricarboxylic acid metabolism increased by 33.18%. The results indicate that metformin has a significant effect on promoting energy metabolism. This study used a combination of metabolomics and metabolic flow to explore the effect of metformin on lipid metabolism disorders and quantifies changes in the key pathway of energy metabolism-the tricarboxylic acid cycle. This study provides useful information for the study of the efficacy and mechanism of metformin, as well as a practical technical method for the screening of lipid-lowering drugs based on a hamster model.

hyperlipidemia  /  metabolomics  /  metabolic flux  /  metformin
Qi-feng LIU, Xue-qi Lü, Cong-cong GUO, Shan-shan SUN, Ya-nan WANG, Xiang-ju JIN, Ying-hong WANG. The effect of metformin on lipid disorders as measured by nuclear magnetic metabolomics and metabolic flux analysis[J]. Acta Pharmaceutica Sinica, 2021 , 56 (4) : 1109 -1119 . DOI: 10.16438/j.0513-4870.2020-1774
Year 2021 volume 56 Issue 4
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doi: 10.16438/j.0513-4870.2020-1774
  • Receive Date:2020-11-08
  • Online Date:2025-12-18
  • Published:2021-04-12
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  • Received:2020-11-08
  • Revised:2021-01-06
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    State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
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表12种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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