The specific mitochondrial unfolded protein response in fast- and slow-twitch muscles of high-fat diet-induced insulin-resistant rats
IntroductionSkeletal muscle insulin resistance (IR) plays an important role in the pathogenesis of type 2 diabetes mellitus. Skeletal muscle is a heterogeneous tissue composed of different muscle fiber types that contribute distinctly to IR development. Glucose transport shows more protection in slo...
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1127524/full |
| _version_ | 1797869543496876032 |
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| author | Can Li Nan Li Ziyi Zhang Yu Song Jialin Li Zhe Wang Hai Bo Hai Bo Yong Zhang |
| author_facet | Can Li Nan Li Ziyi Zhang Yu Song Jialin Li Zhe Wang Hai Bo Hai Bo Yong Zhang |
| author_sort | Can Li |
| collection | DOAJ |
| description | IntroductionSkeletal muscle insulin resistance (IR) plays an important role in the pathogenesis of type 2 diabetes mellitus. Skeletal muscle is a heterogeneous tissue composed of different muscle fiber types that contribute distinctly to IR development. Glucose transport shows more protection in slow-twitch muscles than in fast-twitch muscles during IR development, while the mechanisms involved remain unclear. Therefore, we investigated the role of the mitochondrial unfolded protein response (UPRmt) in the distinct resistance of two types of muscle in IR.MethodsMale Wistar rats were divided into high-fat diet (HFD) feeding and control groups. We measured glucose transport, mitochondrial respiration, UPRmt and histone methylation modification of UPRmt-related proteins to examine the UPRmt in the slow fiber-enriched soleus (Sol) and fast fiber-enriched tibialis anterior (TA) under HFD conditions.ResultsOur results indicate that 18 weeks of HFD can cause systemic IR, while the disturbance of Glut4-dependent glucose transport only occurred in fast-twitch muscle. The expression levels of UPRmt markers, including ATF5, HSP60 and ClpP, and the UPRmt-related mitokine MOTS-c were significantly higher in slow-twitch muscle than in fast-twitch muscle under HFD conditions. Mitochondrial respiratory function is maintained only in slow-twitch muscle. Additionally, in the Sol, histone methylation at the ATF5 promoter region was significantly higher than that in the TA after HFD feeding.ConclusionThe expression of proteins involved in glucose transport in slow-twitch muscle remains almost unaltered after HFD intervention, whereas a significant decline of these proteins was observed in fast-twitch muscle. Specific activation of the UPRmt in slow-twitch muscle, accompanied by higher mitochondrial respiratory function and MOTS-c expression, may contribute to the higher resistance to HFD in slow-twitch muscle. Notably, the different histone modifications of UPRmt regulators may underlie the specific activation of the UPRmt in different muscle types. However, future work applying genetic or pharmacological approaches should further uncover the relationship between the UPRmt and insulin resistance. |
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| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-10T00:13:11Z |
| publishDate | 2023-03-01 |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-5a09d6149b93414dac945a2e07e09deb2023-03-16T07:01:25ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-03-011410.3389/fendo.2023.11275241127524The specific mitochondrial unfolded protein response in fast- and slow-twitch muscles of high-fat diet-induced insulin-resistant ratsCan Li0Nan Li1Ziyi Zhang2Yu Song3Jialin Li4Zhe Wang5Hai Bo6Hai Bo7Yong Zhang8Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, School of Exercise and Health, Tianjin University of Sport, Tianjin, ChinaTianjin Key Laboratory of Exercise Physiology and Sports Medicine, School of Exercise and Health, Tianjin University of Sport, Tianjin, ChinaTianjin Key Laboratory of Exercise Physiology and Sports Medicine, School of Exercise and Health, Tianjin University of Sport, Tianjin, ChinaTianjin Key Laboratory of Exercise Physiology and Sports Medicine, School of Exercise and Health, Tianjin University of Sport, Tianjin, ChinaTianjin Key Laboratory of Exercise Physiology and Sports Medicine, School of Exercise and Health, Tianjin University of Sport, Tianjin, ChinaTianjin Key Laboratory of Exercise Physiology and Sports Medicine, School of Exercise and Health, Tianjin University of Sport, Tianjin, ChinaTianjin Key Laboratory of Exercise Physiology and Sports Medicine, School of Exercise and Health, Tianjin University of Sport, Tianjin, ChinaDepartment of Military Training Medicines, Logistics University of Chinese People’s Armed Police Force, Tianjin, ChinaTianjin Key Laboratory of Exercise Physiology and Sports Medicine, School of Exercise and Health, Tianjin University of Sport, Tianjin, ChinaIntroductionSkeletal muscle insulin resistance (IR) plays an important role in the pathogenesis of type 2 diabetes mellitus. Skeletal muscle is a heterogeneous tissue composed of different muscle fiber types that contribute distinctly to IR development. Glucose transport shows more protection in slow-twitch muscles than in fast-twitch muscles during IR development, while the mechanisms involved remain unclear. Therefore, we investigated the role of the mitochondrial unfolded protein response (UPRmt) in the distinct resistance of two types of muscle in IR.MethodsMale Wistar rats were divided into high-fat diet (HFD) feeding and control groups. We measured glucose transport, mitochondrial respiration, UPRmt and histone methylation modification of UPRmt-related proteins to examine the UPRmt in the slow fiber-enriched soleus (Sol) and fast fiber-enriched tibialis anterior (TA) under HFD conditions.ResultsOur results indicate that 18 weeks of HFD can cause systemic IR, while the disturbance of Glut4-dependent glucose transport only occurred in fast-twitch muscle. The expression levels of UPRmt markers, including ATF5, HSP60 and ClpP, and the UPRmt-related mitokine MOTS-c were significantly higher in slow-twitch muscle than in fast-twitch muscle under HFD conditions. Mitochondrial respiratory function is maintained only in slow-twitch muscle. Additionally, in the Sol, histone methylation at the ATF5 promoter region was significantly higher than that in the TA after HFD feeding.ConclusionThe expression of proteins involved in glucose transport in slow-twitch muscle remains almost unaltered after HFD intervention, whereas a significant decline of these proteins was observed in fast-twitch muscle. Specific activation of the UPRmt in slow-twitch muscle, accompanied by higher mitochondrial respiratory function and MOTS-c expression, may contribute to the higher resistance to HFD in slow-twitch muscle. Notably, the different histone modifications of UPRmt regulators may underlie the specific activation of the UPRmt in different muscle types. However, future work applying genetic or pharmacological approaches should further uncover the relationship between the UPRmt and insulin resistance.https://www.frontiersin.org/articles/10.3389/fendo.2023.1127524/fullinsulin resistanceskeletal muscle fiber typeUPRmtMOTS-cepigenetic modification |
| spellingShingle | Can Li Nan Li Ziyi Zhang Yu Song Jialin Li Zhe Wang Hai Bo Hai Bo Yong Zhang The specific mitochondrial unfolded protein response in fast- and slow-twitch muscles of high-fat diet-induced insulin-resistant rats Frontiers in Endocrinology insulin resistance skeletal muscle fiber type UPRmt MOTS-c epigenetic modification |
| title | The specific mitochondrial unfolded protein response in fast- and slow-twitch muscles of high-fat diet-induced insulin-resistant rats |
| title_full | The specific mitochondrial unfolded protein response in fast- and slow-twitch muscles of high-fat diet-induced insulin-resistant rats |
| title_fullStr | The specific mitochondrial unfolded protein response in fast- and slow-twitch muscles of high-fat diet-induced insulin-resistant rats |
| title_full_unstemmed | The specific mitochondrial unfolded protein response in fast- and slow-twitch muscles of high-fat diet-induced insulin-resistant rats |
| title_short | The specific mitochondrial unfolded protein response in fast- and slow-twitch muscles of high-fat diet-induced insulin-resistant rats |
| title_sort | specific mitochondrial unfolded protein response in fast and slow twitch muscles of high fat diet induced insulin resistant rats |
| topic | insulin resistance skeletal muscle fiber type UPRmt MOTS-c epigenetic modification |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1127524/full |
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