Skeletal-Muscle-Specific Overexpression of Chrono Leads to Disruption of Glucose Metabolism and Exercise Capacity
Disruption of circadian rhythms is related to disorders of glucose metabolism, and the molecular clock also exists in skeletal muscle. The ChIP-derived repressor of network oscillator (Chrono) and brain and muscle ARNT-like 1 (Bmal1) are core circadian components. Chrono is considered to be the repr...
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MDPI AG
2022-08-01
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| Series: | Life |
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| author | Shiyi He Lu Yan Rongxin Zhu Hao Wei Jianxiong Wang Lan Zheng Ying Zhang |
| author_facet | Shiyi He Lu Yan Rongxin Zhu Hao Wei Jianxiong Wang Lan Zheng Ying Zhang |
| author_sort | Shiyi He |
| collection | DOAJ |
| description | Disruption of circadian rhythms is related to disorders of glucose metabolism, and the molecular clock also exists in skeletal muscle. The ChIP-derived repressor of network oscillator (Chrono) and brain and muscle ARNT-like 1 (Bmal1) are core circadian components. Chrono is considered to be the repressor of Bmal1, and the Chrono–Bmal1 pathway is important in regulating the circadian rhythm; it has been speculated that this pathway could be a new mechanism for regulating glucose metabolism. The purpose of this study was to investigate the effects of Chrono on glucose metabolism in skeletal muscle and exercise capacity by using mice with skeletal-muscle-specific overexpression of Chrono (Chrono TG) and wild-type (WT) mice as the animal models. The results of this cross-sectional study indicated that the Chrono TG mice had an impaired glucose tolerance, lower exercise capacity, and higher levels of nonfasted blood glucose and glycogen content in skeletal muscle compared to WT mice. In addition, the Chrono TG mice also showed a significant increase in the amount of Chrono bound to Bmal1 according to a co-IP analysis; a remarkable decrease in mRNA expression of <i>Tbc1d1</i>, <i>Glut4</i>, <i>Hk2</i>, <i>Pfkm</i>, <i>Pdp1</i>, <i>Gbe1</i>, and <i>Phka1</i>, as well as in activity of Hk and protein expression of Ldhb; but higher mRNA expression of <i>Pdk4</i> and protein expression of Ldha compared with those of WT mice. These data suggested the skeletal-muscle-specific overexpression of Chrono led to a greater amount of Chrono bound to Bmal1, which then could affect the glucose transporter, glucose oxidation, and glycogen utilization in skeletal muscle, as well as exercise capacity. |
| first_indexed | 2024-03-09T04:11:33Z |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-09T04:11:33Z |
| publishDate | 2022-08-01 |
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| record_format | Article |
| series | Life |
| spelling | doaj.art-4cbf39a270c042db9661c17694c5aba92023-12-03T13:58:55ZengMDPI AGLife2075-17292022-08-01128123310.3390/life12081233Skeletal-Muscle-Specific Overexpression of Chrono Leads to Disruption of Glucose Metabolism and Exercise CapacityShiyi He0Lu Yan1Rongxin Zhu2Hao Wei3Jianxiong Wang4Lan Zheng5Ying Zhang6Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, Changsha 410012, ChinaSchool of Sport Science, Beijing Sport University, Beijing 100084, ChinaShanghai Research Institute of Sports Science, Shanghai 200030, ChinaSchool of Sport Science, Beijing Sport University, Beijing 100084, ChinaFaculty of Health, Engineering, and Sciences, University of Southern Queensland, Toowoomba, QLD 4350, AustraliaKey Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, Changsha 410012, ChinaSchool of Sport Science, Beijing Sport University, Beijing 100084, ChinaDisruption of circadian rhythms is related to disorders of glucose metabolism, and the molecular clock also exists in skeletal muscle. The ChIP-derived repressor of network oscillator (Chrono) and brain and muscle ARNT-like 1 (Bmal1) are core circadian components. Chrono is considered to be the repressor of Bmal1, and the Chrono–Bmal1 pathway is important in regulating the circadian rhythm; it has been speculated that this pathway could be a new mechanism for regulating glucose metabolism. The purpose of this study was to investigate the effects of Chrono on glucose metabolism in skeletal muscle and exercise capacity by using mice with skeletal-muscle-specific overexpression of Chrono (Chrono TG) and wild-type (WT) mice as the animal models. The results of this cross-sectional study indicated that the Chrono TG mice had an impaired glucose tolerance, lower exercise capacity, and higher levels of nonfasted blood glucose and glycogen content in skeletal muscle compared to WT mice. In addition, the Chrono TG mice also showed a significant increase in the amount of Chrono bound to Bmal1 according to a co-IP analysis; a remarkable decrease in mRNA expression of <i>Tbc1d1</i>, <i>Glut4</i>, <i>Hk2</i>, <i>Pfkm</i>, <i>Pdp1</i>, <i>Gbe1</i>, and <i>Phka1</i>, as well as in activity of Hk and protein expression of Ldhb; but higher mRNA expression of <i>Pdk4</i> and protein expression of Ldha compared with those of WT mice. These data suggested the skeletal-muscle-specific overexpression of Chrono led to a greater amount of Chrono bound to Bmal1, which then could affect the glucose transporter, glucose oxidation, and glycogen utilization in skeletal muscle, as well as exercise capacity.https://www.mdpi.com/2075-1729/12/8/1233glucose metabolismskeletal muscleChronoexercise capacitymice |
| spellingShingle | Shiyi He Lu Yan Rongxin Zhu Hao Wei Jianxiong Wang Lan Zheng Ying Zhang Skeletal-Muscle-Specific Overexpression of Chrono Leads to Disruption of Glucose Metabolism and Exercise Capacity Life glucose metabolism skeletal muscle Chrono exercise capacity mice |
| title | Skeletal-Muscle-Specific Overexpression of Chrono Leads to Disruption of Glucose Metabolism and Exercise Capacity |
| title_full | Skeletal-Muscle-Specific Overexpression of Chrono Leads to Disruption of Glucose Metabolism and Exercise Capacity |
| title_fullStr | Skeletal-Muscle-Specific Overexpression of Chrono Leads to Disruption of Glucose Metabolism and Exercise Capacity |
| title_full_unstemmed | Skeletal-Muscle-Specific Overexpression of Chrono Leads to Disruption of Glucose Metabolism and Exercise Capacity |
| title_short | Skeletal-Muscle-Specific Overexpression of Chrono Leads to Disruption of Glucose Metabolism and Exercise Capacity |
| title_sort | skeletal muscle specific overexpression of chrono leads to disruption of glucose metabolism and exercise capacity |
| topic | glucose metabolism skeletal muscle Chrono exercise capacity mice |
| url | https://www.mdpi.com/2075-1729/12/8/1233 |
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