Increased glucose metabolism inArid5b-/-skeletal muscle is associated with the down-regulation of TBC1 domain family member 1 (TBC1D1)

被引:12
|
作者
Okazaki, Yuri [1 ,2 ,3 ]
Murray, Jennifer [1 ]
Ehsani, Ali [1 ]
Clark, Jessica [1 ]
Whitson, Robert H. [1 ]
Hirose, Lisa [1 ]
Yanaka, Noriyuki [2 ]
Itakura, Keiichi [1 ]
机构
[1] Beckman Res Inst, Dept Mol & Cellular Biol, City Hope, Duarte, CA 91010 USA
[2] Hiroshima Univ, Grad Sch Biosphere Sci, Dept Mol & Appl Biosci, Higashihiroshima, Hiroshima, Japan
[3] Wakunaga Pharmaceut Co Ltd, Dept Cent Res Inst, Akitakata, Hiroshima, Japan
关键词
Arid5b; Glucose metabolism; GLUT4; translocation; SKELETAL-MUSCLE; INSULIN; PROTEIN; CELLS; PHOSPHORYLATION; EXPRESSION; ROLES;
D O I
10.1186/s40659-020-00313-3
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 ofArid5bin energy metabolism has been suggested in adipocytes and hepatocytes, the role ofArid5bin skeletal muscle metabolism has not been studied. Therefore, we investigated whether energy metabolism is altered inArid5b(-/-)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 inArid5b(-/-)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 inArid5b(-/-)skeletal muscle. Coimmunofluorescence staining of the GC muscle sections for GLUT4 and dystrophin revealed increased GLUT4 localization at the plasma membrane inArid5b(-/-)muscle. Conclusions The current study showed that the knockout ofArid5benhanced glucose metabolism through the downregulation of TBC1D1 and increased GLUT4 membrane translocation in skeletal muscle.
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页数:14
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