| Autor: |
Duo Zhang, Yan Li, Xuan Yao, Hui Wang, Lei Zhao, Haowen Jiang, Xiaohan Yao, Shengjie Zhang, Cheng Ye, Wei Liu, Hongchao Cao, Shuxian Yu, Yu-cheng Wang, Qiong Li, Jingjing Jiang, Yi Liu, Ling Zhang, Yun Liu, Naoharu Iwai, Jingya Li, Jia Li, Xihua Li, Zi-Bing Jin, Hao Ying |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 16, Iss 3, Pp 757-768 (2016) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2016.06.040 |
| Popis: |
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 α (TNFα), 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
