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Objective To analyze the mechanism of skeletal muscle atrophy in mice caused by Opg gene knockout based on metabolomics. Methods Five 3-month-old wild-type C57BL/6 male mice and five 3-month-old male Opg gene knockout mice were set as wild-type group and gene knockout group, respectively. Left femur and gastrocnemius muscle of mice were taken for evaluating the bone microstructure with micro-CT scanning and observing the morphological changes of gastrocnemius muscle by HE staining; The spermidine content in gastrocnemius muscle was detected by immunofluorescence staining. Ten 3-month-old male wild-type C57BL/6 mice, ten 3-month-old male Opg knockout mice and ten 18-month-old male wild-type C57BL/6 mice were set as young wild-type (WT-Y) group, young knockout (OPG-Y) group and old wild-type (WT-O) group, which were used for gastrocnemius metabolomics analysis. Results Compared with wild-type mice, Opg knockout mice showed fewer bone trabeculae, decreased bone density, cortical bone structure was destroyed, the weight of gastrocnemius muscle and the cross sectional area of gastrocnemius fiber were decreased (P<0.05). Metabolomics analysis showed that, compared with WT-Y mice, metabolites involved in glucose, phospholipid and amino acid metabolism, such as glucose-1-phosphate, D-glucose-1, 6-bisphosphate, multiple amino acids, choline, carnitine etc. were significantly up-regulated in WT-O mice, while γ-aminobutyric acid, spermidine, pantothenate etc. were significantly down-regulated. Compared with WT-Y mice, metabolites such as choline, β-glycerophosphate, azelaic acid etc. were up-regulated in OPG-Y mice, while other metabolites such as spermidine, pantothenate, N6, N6, N6-trimethyl-lysine etc. were significantly down-regulated, which were mainly involved in amino acid metabolism. The validation results of metabolomics analysis suggested that the content of spermidine in gastrocnemius of Opg knockout mice was significantly lower than that of WT-Y mice (P<0.01). Conclusion Opg knockout may regulate the levels of metabolites such as spermidine and regulate the level of metabolites such as spermidine and pantothenic acid through amino acid metabolism and other pathways, which cause skeletal muscle atrophy.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 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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