Increased glucose metabolism in Arid5b −/− skeletal muscle is associated with the down-regulation of TBC1 domain family member 1 (TBC1D1)
Abstract Background Skeletal muscle has an important role in regulating whole-body energy homeostasis, and energy production depends on the efficient function of mitochondria. We demonstrated previously that AT-rich interactive domain 5b (Arid5b) knockout (Arid5b −/− ) mice were lean and resistant t...
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doaj-1c9b9c05dae14fe4aa3256bec32d8f6c2020-11-25T03:55:45ZengBMCBiological Research0717-62872020-10-0153111410.1186/s40659-020-00313-3Increased glucose metabolism in Arid5b −/− skeletal muscle is associated with the down-regulation of TBC1 domain family member 1 (TBC1D1)Yuri Okazaki0Jennifer Murray1Ali Ehsani2Jessica Clark3Robert H. Whitson4Lisa Hirose5Noriyuki Yanaka6Keiichi Itakura7Department of Molecular and Cellular Biology, Beckman Research Institute, City of HopeDepartment of Molecular and Cellular Biology, Beckman Research Institute, City of HopeDepartment of Molecular and Cellular Biology, Beckman Research Institute, City of HopeDepartment of Molecular and Cellular Biology, Beckman Research Institute, City of HopeDepartment of Molecular and Cellular Biology, Beckman Research Institute, City of HopeDepartment of Molecular and Cellular Biology, Beckman Research Institute, City of HopeDepartment of Molecular and Applied Bioscience, Graduate School of Biosphere Science, Hiroshima UniversityDepartment of Molecular and Cellular Biology, Beckman Research Institute, City of HopeAbstract Background Skeletal muscle has an important role in regulating whole-body energy homeostasis, and energy production depends on the efficient function of mitochondria. We demonstrated previously that AT-rich interactive domain 5b (Arid5b) knockout (Arid5b −/− ) mice were lean and resistant to high-fat diet (HFD)-induced obesity. While a potential role of Arid5b in energy metabolism has been suggested in adipocytes and hepatocytes, the role of Arid5b in skeletal muscle metabolism has not been studied. Therefore, we investigated whether energy metabolism is altered in Arid5b −/− skeletal muscle. Results Arid5b −/− skeletal muscles showed increased basal glucose uptake, glycogen content, glucose oxidation and ATP content. Additionally, glucose clearance and oxygen consumption were upregulated in Arid5b −/− mice. The expression of glucose transporter 1 (GLUT1) and 4 (GLUT4) in the gastrocnemius (GC) muscle remained unchanged. Intriguingly, the expression of TBC domain family member 1 (TBC1D1), which negatively regulates GLUT4 translocation to the plasma membrane, was suppressed in Arid5b −/− skeletal muscle. Coimmunofluorescence staining of the GC muscle sections for GLUT4 and dystrophin revealed increased GLUT4 localization at the plasma membrane in Arid5b −/− muscle. Conclusions The current study showed that the knockout of Arid5b enhanced glucose metabolism through the downregulation of TBC1D1 and increased GLUT4 membrane translocation in skeletal muscle.http://link.springer.com/article/10.1186/s40659-020-00313-3Arid5bGlucose metabolismTBC1D1GLUT4 translocation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yuri Okazaki Jennifer Murray Ali Ehsani Jessica Clark Robert H. Whitson Lisa Hirose Noriyuki Yanaka Keiichi Itakura |
spellingShingle |
Yuri Okazaki Jennifer Murray Ali Ehsani Jessica Clark Robert H. Whitson Lisa Hirose Noriyuki Yanaka Keiichi Itakura Increased glucose metabolism in Arid5b −/− skeletal muscle is associated with the down-regulation of TBC1 domain family member 1 (TBC1D1) Biological Research Arid5b Glucose metabolism TBC1D1 GLUT4 translocation |
author_facet |
Yuri Okazaki Jennifer Murray Ali Ehsani Jessica Clark Robert H. Whitson Lisa Hirose Noriyuki Yanaka Keiichi Itakura |
author_sort |
Yuri Okazaki |
title |
Increased glucose metabolism in Arid5b −/− skeletal muscle is associated with the down-regulation of TBC1 domain family member 1 (TBC1D1) |
title_short |
Increased glucose metabolism in Arid5b −/− skeletal muscle is associated with the down-regulation of TBC1 domain family member 1 (TBC1D1) |
title_full |
Increased glucose metabolism in Arid5b −/− skeletal muscle is associated with the down-regulation of TBC1 domain family member 1 (TBC1D1) |
title_fullStr |
Increased glucose metabolism in Arid5b −/− skeletal muscle is associated with the down-regulation of TBC1 domain family member 1 (TBC1D1) |
title_full_unstemmed |
Increased glucose metabolism in Arid5b −/− skeletal muscle is associated with the down-regulation of TBC1 domain family member 1 (TBC1D1) |
title_sort |
increased glucose metabolism in arid5b −/− skeletal muscle is associated with the down-regulation of tbc1 domain family member 1 (tbc1d1) |
publisher |
BMC |
series |
Biological Research |
issn |
0717-6287 |
publishDate |
2020-10-01 |
description |
Abstract Background Skeletal muscle has an important role in regulating whole-body energy homeostasis, and energy production depends on the efficient function of mitochondria. We demonstrated previously that AT-rich interactive domain 5b (Arid5b) knockout (Arid5b −/− ) mice were lean and resistant to high-fat diet (HFD)-induced obesity. While a potential role of Arid5b in energy metabolism has been suggested in adipocytes and hepatocytes, the role of Arid5b in skeletal muscle metabolism has not been studied. Therefore, we investigated whether energy metabolism is altered in Arid5b −/− skeletal muscle. Results Arid5b −/− skeletal muscles showed increased basal glucose uptake, glycogen content, glucose oxidation and ATP content. Additionally, glucose clearance and oxygen consumption were upregulated in Arid5b −/− mice. The expression of glucose transporter 1 (GLUT1) and 4 (GLUT4) in the gastrocnemius (GC) muscle remained unchanged. Intriguingly, the expression of TBC domain family member 1 (TBC1D1), which negatively regulates GLUT4 translocation to the plasma membrane, was suppressed in Arid5b −/− skeletal muscle. Coimmunofluorescence staining of the GC muscle sections for GLUT4 and dystrophin revealed increased GLUT4 localization at the plasma membrane in Arid5b −/− muscle. Conclusions The current study showed that the knockout of Arid5b enhanced glucose metabolism through the downregulation of TBC1D1 and increased GLUT4 membrane translocation in skeletal muscle. |
topic |
Arid5b Glucose metabolism TBC1D1 GLUT4 translocation |
url |
http://link.springer.com/article/10.1186/s40659-020-00313-3 |
work_keys_str_mv |
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