| First Author | Sadagurski M | Year | 2012 |
| Journal | Cell Metab | Volume | 15 |
| Issue | 5 | Pages | 703-12 |
| PubMed ID | 22560222 | Mgi Jnum | J:184780 |
| Mgi Id | MGI:5426311 | Doi | 10.1016/j.cmet.2012.04.011 |
| Citation | Sadagurski M, et al. (2012) IRS2 signaling in LepR-b neurons suppresses FoxO1 to control energy balance independently of leptin action. Cell Metab 15(5):703-12 |
| abstractText | Irs2-mediated insulin/IGF1 signaling in the CNS modulates energy balance and glucose homeostasis; however, the site for Irs2 function is unknown. The hormone leptin mediates energy balance by acting on leptin receptor (LepR-b)-expressing neurons. To determine whether LepR-b neurons mediate the metabolic actions of Irs2 in the brain, we utilized Lepr(cre) together with Irs2(L/L) to ablate Irs2 expression in LepR-b neurons (Lepr(DeltaIrs2)). Lepr(DeltaIrs2) mice developed obesity, glucose intolerance, and insulin resistance. Leptin action was not altered in young Lepr(DeltaIrs2) mice, although insulin-stimulated FoxO1 nuclear exclusion was reduced in Lepr(DeltaIrs2) mice. Indeed, deletion of Foxo1 from LepR-b neurons in Lepr(DeltaIrs2) mice normalized energy balance, glucose homeostasis, and arcuate nucleus gene expression. Thus, Irs2 signaling in LepR-b neurons plays a crucial role in metabolic sensing and regulation. While not required for leptin action, Irs2 suppresses FoxO1 signaling in LepR-b neurons to promote energy balance and metabolism. |
