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. 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. 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.

中文翻译：

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Arid5b-/- 骨骼肌中葡萄糖代谢增加与 TBC1 结构域家族成员 1 (TBC1D1) 的下调有关

骨骼肌在调节全身能量稳态中具有重要作用，而能量产生依赖于线粒体的高效功能。我们之前证明了富含 AT 的交互域 5b (Arid5b) 敲除 (Arid5b-/-) 小鼠是瘦的并且对高脂饮食 (HFD) 诱导的肥胖具有抵抗力。虽然已经在脂肪细胞和肝细胞中提出了 Arid5b 在能量代谢中的潜在作用，但尚未研究 Arid5b 在骨骼肌代谢中的作用。因此，我们研究了 Arid5b-/- 骨骼肌中的能量代谢是否发生了改变。Arid5b-/- 骨骼肌显示基础葡萄糖摄取、糖原含量、葡萄糖氧化和 ATP 含量增加。此外，Arid5b-/- 小鼠的葡萄糖清除率和耗氧量上调。腓肠肌 (GC) 肌肉中葡萄糖转运蛋白 1 (GLUT1) 和 4 (GLUT4) 的表达保持不变。有趣的是，TBC 结构域家族成员 1 (TBC1D1) 的表达在 Arid5b-/- 骨骼肌中被抑制，它负向调节 GLUT4 易位至质膜。GC 肌肉切片的 GLUT4 和肌营养不良蛋白的共免疫荧光染色显示，在 Arid5b-/- 肌肉中，GLUT4 在质膜上的定位增加。目前的研究表明，敲除 Arid5b 通过下调 TBC1D1 和增加骨骼肌中 GLUT4 膜易位来增强葡萄糖代谢。在 Arid5b-/- 骨骼肌中被抑制。GC 肌肉切片的 GLUT4 和肌营养不良蛋白的共免疫荧光染色显示，在 Arid5b-/- 肌肉中，GLUT4 在质膜上的定位增加。目前的研究表明，敲除 Arid5b 通过下调 TBC1D1 和增加骨骼肌中 GLUT4 膜易位来增强葡萄糖代谢。在 Arid5b-/- 骨骼肌中被抑制。GC 肌肉切片的 GLUT4 和肌营养不良蛋白的共免疫荧光染色显示，在 Arid5b-/- 肌肉中，GLUT4 在质膜上的定位增加。目前的研究表明，敲除 Arid5b 通过下调 TBC1D1 和增加骨骼肌中 GLUT4 膜易位来增强葡萄糖代谢。