Skeletal-Muscle-Specific Overexpression of Chrono Leads to Disruption of Glucose Metabolism and Exercise Capacity

Article


He, Shiyi, Yan, Lu, Zhu, Rongxin, Wei, Hao, Wang, Jianxiong, Zheng, Lan and Zhang, Ying. 2022. "Skeletal-Muscle-Specific Overexpression of Chrono Leads to Disruption of Glucose Metabolism and Exercise Capacity." Life. 12 (8). https://doi.org/10.3390/life12081233
Article Title

Skeletal-Muscle-Specific Overexpression of Chrono Leads to Disruption of Glucose Metabolism and Exercise Capacity

ERA Journal ID213583
Article CategoryArticle
AuthorsHe, Shiyi, Yan, Lu, Zhu, Rongxin, Wei, Hao, Wang, Jianxiong, Zheng, Lan and Zhang, Ying
Journal TitleLife
Journal Citation12 (8)
Article Number1233
Number of Pages12
Year2022
PublisherMDPI AG
Place of PublicationSwitzerland
ISSN2075-1729
Digital Object Identifier (DOI)https://doi.org/10.3390/life12081233
Web Address (URL)https://www.mdpi.com/2075-1729/12/8/1233
Abstract

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 Tbc1d1, Glut4, Hk2, Pfkm, Pdp1, Gbe1, and Phka1, as well as in activity of Hk and protein expression of Ldhb; but higher mRNA expression of Pdk4 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.

Keywordsexercise capacity; glucose metabolism; skeletal muscle; Chrono; mice
Byline AffiliationsHunan Normal University, China
Beijing Sport University, China
Shanghai Research Institute of Sports Science, China
University of Southern Queensland
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