| First Author | Yagishita Y | Year | 2017 |
| Journal | Cell Rep | Volume | 18 |
| Issue | 8 | Pages | 2030-2044 |
| PubMed ID | 28228267 | Mgi Jnum | J:250943 |
| Mgi Id | MGI:6102995 | Doi | 10.1016/j.celrep.2017.01.064 |
| Citation | Yagishita Y, et al. (2017) Nrf2 Improves Leptin and Insulin Resistance Provoked by Hypothalamic Oxidative Stress. Cell Rep 18(8):2030-2044 |
| abstractText | The relationship between loss of hypothalamic function and onset of diabetes mellitus remains elusive. Therefore, we generated a targeted oxidative-stress murine model utilizing conditional knockout (KO) of selenocysteine-tRNA (Trsp) using rat-insulin-promoter-driven-Cre (RIP-Cre). These Trsp-KO (Trsp(RIP)KO) mice exhibit deletion of Trsp in both hypothalamic cells and pancreatic beta cells, leading to increased hypothalamic oxidative stress and severe insulin resistance. Leptin signals are suppressed, and numbers of proopiomelanocortin-positive neurons in the hypothalamus are decreased. In contrast, Trsp-KO mice (Trsp(Ins1)KO) expressing Cre specifically in pancreatic beta cells, but not in the hypothalamus, do not display insulin and leptin resistance, demonstrating a critical role of the hypothalamus in the onset of diabetes mellitus. Nrf2 (NF-E2-related factor 2) regulates antioxidant gene expression. Increased Nrf2 signaling suppresses hypothalamic oxidative stress and improves insulin and leptin resistance in Trsp(RIP)KO mice. Thus, Nrf2 harbors the potential to prevent the onset of diabetic mellitus by reducing hypothalamic oxidative damage. |
