| First Author | Liu W | Year | 2014 |
| Journal | Nat Commun | Volume | 5 |
| Pages | 5684 | PubMed ID | 25471065 |
| Mgi Jnum | J:225687 | Mgi Id | MGI:5694025 |
| Doi | 10.1038/ncomms6684 | Citation | Liu W, et al. (2014) Hepatic miR-378 targets p110alpha and controls glucose and lipid homeostasis by modulating hepatic insulin signalling. Nat Commun 5:5684 |
| abstractText | Understanding the regulation of insulin signalling in tissues provides insights into carbohydrate and lipid metabolism in physiology and disease. Here we show that hepatic miR-378/378* expression changes in response to fasting and refeeding in mice. Mice overexpressing hepatic miR-378/378* exhibit pure hepatic insulin resistance. miR-378 inhibits hepatic insulin signalling through targeting p110alpha, a subunit of PI3K and hence a critical component of insulin signalling. Knockdown of hepatic p110alpha mimics the effect of miR-378, while restoration of p110alpha expression abolishes the action of miR-378 on insulin signalling as well as its systemic effects on glucose and lipid homeostasis. miR-378/378* knockout mice display hypoglycemia and increased hepatic triglyceride level with enhanced insulin sensitivity. Inhibition of hepatic p110alpha in miR-378/378* knockout mice corrects the abnormal glucose tolerance. Finally, we show that overexpression of hepatic miR-378/378* ameliorates hepatic steatosis in ob/ob mice without exacerbating hyperglycemia. Our findings establish fasting-responsive miR-378 as a critical regulator of hepatic insulin signalling. |
