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| Status |
Public on May 11, 2024 |
| Title |
Skeletal muscle cystathionine γ-lyase deficiency promotes obesity and insulin resistance and results in hyperglycemia and skeletal muscle injury upon HFD in mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
In the present study, we explored whether skeletal muscle cystathionine γ-lyase (CTH) contributes to high-fat diet (HFD)-induced metabolic disorders using skeletal muscle Cth knockout (CthΔskm) mice. Metabolomics coupled with transcriptome showed that CthΔskm mice displayed impaired energy metabolism and some signaling pathways linked to insulin resistance (IR) in skeletal muscle although the mice had normal insulin sensitivity. HFD led to reduced CTH expression and impaired energy metabolism in skeletal muscle in Cth-floxed mice (Cthf/f) mice. CTH deficiency and HFD had some common pathways enriched in the aspects of amino acid metabolism, carbon metabolism, and fatty acid metabolism. CthΔskm+HFD mice exhibited increased body weight gain, fasting blood glucose, plasma insulin, and IR, and reduced glucose transporter 4 and CD36 expression in skeletal muscle compared to Cthf/f+HFD mice. Impaired mitochondria and irregular arrangement in myofilament occurred in CthΔskm+HFD mice. Omics analysis showed differential pathways enriched between CthΔskm mice and Cthf/f mice upon HFD. More severity in impaired energy metabolism, reduced AMPK signaling, and increased oxidative stress and ferroptosis occurred in CthΔskm+HFD mice compared to Cthf/f+HFD mice. Our data indicate that skeletal muscle CTH expression dysregulation contributes to metabolism disorders upon HFD.
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| Overall design |
The WT and CSE∆skm mice were fed with HFD or chow from 4-weeks old for 13 weeks. The mice were sacrificed under deep anesthesia at 17-weeks old. Gastronemius was obtained for RNA-seq analysis.
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| Contributor(s) |
Lu J, Tang Z, Xu M, Lu J, Wang C, Yu B, Ni X |
| Citation missing |
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| Submission date |
Jan 31, 2024 |
| Last update date |
May 11, 2024 |
| Contact name |
Jiani Lu |
| Organization name |
Shanghai General Hospital
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| Street address |
No.85 Wujin Rd.
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| City |
Shanghai |
| ZIP/Postal code |
200080 |
| Country |
China |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (32)
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| Relations |
| BioProject |
PRJNA1071548 |
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