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论文题目: miR-182 Regulates Metabolic Homeostasis by Modulating Glucose Utilization in Muscle
英文论文题目: miR-182 Regulates Metabolic Homeostasis by Modulating Glucose Utilization in Muscle
第一作者: Zhang, D; Li, Y; Yao, X; Wang, H; Zhao, L; Jiang, HW; Yao, XH; Zhang, SJ; Ye, C; Liu, W; Cao, HC; Yu, SX; Wang, YC; Li, Q; Jiang, JJ; Liu, Y; Zhang, L; Liu, Y; Iwai, N; Wang, H; Li, JY; Li, J; Li, XH; Jin, ZB; Ying, H
英文第一作者: Zhang, D; Li, Y; Yao, X; Wang, H; Zhao, L; Jiang, HW; Yao, XH; Zhang, SJ; Ye, C; Liu, W; Cao, HC; Yu, SX; Wang, YC; Li, Q; Jiang, JJ; Liu, Y; Zhang, L; Liu, Y; Iwai, N; Wang, H; Li, JY; Li, J; Li, XH; Jin, ZB; Ying, H
联系作者: Ying, H (reprint author), Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Food Safety Res,Inst Nutr Sci, Shanghai 200031, Peoples R China.
英文联系作者: Ying, H (reprint author), Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Food Safety Res,Inst Nutr Sci, Shanghai 200031, Peoples R China.
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发表年度: 2016
卷: 16
期: 3
页码: 757-768
摘要: 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 alpha (TNF alpha), 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.
英文摘要: 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 alpha (TNF alpha), 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.
刊物名称: CELL REPORTS
英文刊物名称: CELL REPORTS
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学科: Cell Biology
英文学科: Cell Biology
影响因子: 8.282
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论文类别: Article
英文论文类别: Article
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