Skeletal Muscle CSE Deficiency Leads to Insulin Resistance in Mice
Cystathionine-γ-lyase (CSE) is expressed in various tissues and generates H<sub>2</sub>S via an alternative desulfuration reaction. We sought to explore the functions of skeletal muscle CSE using skeletal muscle conditional knockout CSE (MCSEKO) mice. It was found that body weight, muscl...
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MDPI AG
2022-11-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/11/2216 |
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| author | Miaomiao Xu Xiaoguang Liu Peng Bao Yanjie Wang Xiaoyan Zhu Yujian Liu Xin Ni Jianqiang Lu |
| author_facet | Miaomiao Xu Xiaoguang Liu Peng Bao Yanjie Wang Xiaoyan Zhu Yujian Liu Xin Ni Jianqiang Lu |
| author_sort | Miaomiao Xu |
| collection | DOAJ |
| description | Cystathionine-γ-lyase (CSE) is expressed in various tissues and generates H<sub>2</sub>S via an alternative desulfuration reaction. We sought to explore the functions of skeletal muscle CSE using skeletal muscle conditional knockout CSE (MCSEKO) mice. It was found that body weight, muscle morphology, and exercise capacity were not altered in MCSEKO mice compared with littermate wild-type mice. RNA-seq-based transcriptome analysis showed that 275 genes were differentially regulated in skeletal muscle and multiple signaling pathways including insulin signaling and mTOR, PI3K-AKT, and cGMP-PKG signaling pathways were enriched in MCSEKO mice. The intraperitoneal glucose tolerance test and insulin tolerance test showed that glucose tolerance and insulin sensitivity were reduced in MCSEKO mice. Glucose transporter 4 (GLU4) and PKG-1 expression levels and insulin receptor substrate-1(IRS1)/PI3K/Akt signaling pathway were downregulated whilst the mTOR/S6K/S6 pathway was enhanced in MCSEKO mice. These effects were reversed by the H<sub>2</sub>S supplement. Aerobic treadmill training significantly promoted glucose tolerance and insulin sensitivity and improved GLU4 and PKG-1 levels, promoted IRS1/PI3K/Akt signaling and suppressed mTOR/S6K/S6 signaling pathway in MCSEKO mice. Our data suggest that skeletal muscle CSE/H<sub>2</sub>S signaling is critical for the maintenance of insulin sensitivity, which is associated with maintaining the balance in PKG, PI3K/Akt, and mTOR/S6K/S6 signaling pathways in skeletal muscle. |
| first_indexed | 2024-03-09T19:19:11Z |
| format | Article |
| id | doaj.art-85ba1776bf0740458197e5a98d41aaac |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T19:19:11Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-85ba1776bf0740458197e5a98d41aaac2023-11-24T03:31:08ZengMDPI AGAntioxidants2076-39212022-11-011111221610.3390/antiox11112216Skeletal Muscle CSE Deficiency Leads to Insulin Resistance in MiceMiaomiao Xu0Xiaoguang Liu1Peng Bao2Yanjie Wang3Xiaoyan Zhu4Yujian Liu5Xin Ni6Jianqiang Lu7School of Exercise and Health, Shanghai University of Sport, Shanghai 200438, ChinaSchool of Sport and Health, Guangzhou Sport University, Guangzhou 510500, ChinaSchool of Exercise and Health, Shanghai University of Sport, Shanghai 200438, ChinaSchool of Exercise and Health, Shanghai University of Sport, Shanghai 200438, ChinaDepartment of Physiology, Navy Medical University, Shanghai 200433, ChinaSchool of Exercise and Health, Shanghai University of Sport, Shanghai 200438, ChinaResearch Center for Molecular Metabolomic, Xiangya Hospital Central South University, Changsha 410008, ChinaSchool of Exercise and Health, Shanghai University of Sport, Shanghai 200438, ChinaCystathionine-γ-lyase (CSE) is expressed in various tissues and generates H<sub>2</sub>S via an alternative desulfuration reaction. We sought to explore the functions of skeletal muscle CSE using skeletal muscle conditional knockout CSE (MCSEKO) mice. It was found that body weight, muscle morphology, and exercise capacity were not altered in MCSEKO mice compared with littermate wild-type mice. RNA-seq-based transcriptome analysis showed that 275 genes were differentially regulated in skeletal muscle and multiple signaling pathways including insulin signaling and mTOR, PI3K-AKT, and cGMP-PKG signaling pathways were enriched in MCSEKO mice. The intraperitoneal glucose tolerance test and insulin tolerance test showed that glucose tolerance and insulin sensitivity were reduced in MCSEKO mice. Glucose transporter 4 (GLU4) and PKG-1 expression levels and insulin receptor substrate-1(IRS1)/PI3K/Akt signaling pathway were downregulated whilst the mTOR/S6K/S6 pathway was enhanced in MCSEKO mice. These effects were reversed by the H<sub>2</sub>S supplement. Aerobic treadmill training significantly promoted glucose tolerance and insulin sensitivity and improved GLU4 and PKG-1 levels, promoted IRS1/PI3K/Akt signaling and suppressed mTOR/S6K/S6 signaling pathway in MCSEKO mice. Our data suggest that skeletal muscle CSE/H<sub>2</sub>S signaling is critical for the maintenance of insulin sensitivity, which is associated with maintaining the balance in PKG, PI3K/Akt, and mTOR/S6K/S6 signaling pathways in skeletal muscle.https://www.mdpi.com/2076-3921/11/11/2216H<sub>2</sub>Scystathionine-γ-lyaseskeletal muscleglucose toleranceinsulin resistanceexercise |
| spellingShingle | Miaomiao Xu Xiaoguang Liu Peng Bao Yanjie Wang Xiaoyan Zhu Yujian Liu Xin Ni Jianqiang Lu Skeletal Muscle CSE Deficiency Leads to Insulin Resistance in Mice Antioxidants H<sub>2</sub>S cystathionine-γ-lyase skeletal muscle glucose tolerance insulin resistance exercise |
| title | Skeletal Muscle CSE Deficiency Leads to Insulin Resistance in Mice |
| title_full | Skeletal Muscle CSE Deficiency Leads to Insulin Resistance in Mice |
| title_fullStr | Skeletal Muscle CSE Deficiency Leads to Insulin Resistance in Mice |
| title_full_unstemmed | Skeletal Muscle CSE Deficiency Leads to Insulin Resistance in Mice |
| title_short | Skeletal Muscle CSE Deficiency Leads to Insulin Resistance in Mice |
| title_sort | skeletal muscle cse deficiency leads to insulin resistance in mice |
| topic | H<sub>2</sub>S cystathionine-γ-lyase skeletal muscle glucose tolerance insulin resistance exercise |
| url | https://www.mdpi.com/2076-3921/11/11/2216 |
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