| First Author | Zhang D | Year | 2016 |
| Journal | Cell Rep | Volume | 16 |
| Issue | 3 | Pages | 757-68 |
| PubMed ID | 27396327 | Mgi Jnum | J:238680 |
| Mgi Id | MGI:5823345 | Doi | 10.1016/j.celrep.2016.06.040 |
| Citation | Zhang D, et al. (2016) miR-182 Regulates Metabolic Homeostasis by Modulating Glucose Utilization in Muscle. Cell Rep 16(3):757-68 |
| abstractText | 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 (TNFalpha), 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. |
