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miR-182 Regulates Metabolic Homeostasis by Modulating Glucose Utilization in Muscle

机译:miR-182通过调节肌肉中的葡萄糖利用来调节代谢稳态。

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Understanding the fiber-type specification and metabolic switch in skeletal muscle provides insights into energy metabolism in physiology and diseases. Here, we show that miR-182 is highly expressed in fast-twitch muscle and negatively correlates with blood glucose level. miR-182 knockout mice display muscle loss, fast-to-slow fiber-type switching, and impaired glucose metabolism. Mechanistic studies reveal that miR-182 modulates glucose utilization in muscle by targeting FoxO1 and PDK4, which control fuel selection via the pyruvate dehydrogenase complex (PDHC). Short-term high-fat diet (HFD) feeding reduces muscle miR-182 levels by tumor necrosis factor @a (TNF@a), which contributes to the upregulation of FoxO1/PDK4. Restoration of miR-182 expression in HFD-fed mice induces a faster muscle phenotype, decreases muscle FoxO1/PDK4 levels, and improves glucose metabolism. Together, our work establishes miR-182 as a critical regulator that confers robust and precise controls on fuel usage and glucose homeostasis. Our study suggests that a metabolic shift toward a faster and more glycolytic phenotype is beneficial for glucose control.
机译:了解骨骼肌的纤维类型规格和代谢转换可提供有关生理和疾病中能量代谢的见解。在这里,我们显示了miR-182在快速抽搐的肌肉中高度表达,并且与血糖水平呈负相关。 miR-182剔除小鼠表现出肌肉损失,快速至慢速的纤维类型转换和葡萄糖代谢受损。机理研究表明,miR-182通过靶向FoxO1和PDK4调节肌肉中的葡萄糖利用,后者通过丙酮酸脱氢酶复合物(PDHC)控制燃料的选择。短期高脂饮食(HFD)会通过肿瘤坏死因子@a(TNF @ a)降低肌肉miR-182水平,这有助于FoxO1 / PDK4的上调。在饲喂HFD的小鼠中,miR-182表达的恢复可诱导更快的肌肉表型,降低肌肉FoxO1 / PDK4的水平,并改善葡萄糖代谢。在一起,我们的工作将miR-182确立为一个关键的调节器,可对燃料使用和葡萄糖动态平衡进行稳健而精确的控制。我们的研究表明,向更快,更强糖酵解表型的代谢转变对控制血糖是有益的。

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