| First Author | Zhang Y | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 3 | Pages | 113900 |
| PubMed ID | 38460132 | Mgi Jnum | J:346744 |
| Mgi Id | MGI:7618042 | Doi | 10.1016/j.celrep.2024.113900 |
| Citation | Zhang Y, et al. (2024) Iron overload in hypothalamic AgRP neurons contributes to obesity and related metabolic disorders. Cell Rep 43(3):113900 |
| abstractText | Iron overload is closely associated with metabolic dysfunction. However, the role of iron in the hypothalamus remains unclear. Here, we find that hypothalamic iron levels are increased, particularly in agouti-related peptide (AgRP)-expressing neurons in high-fat-diet-fed mice. Using pharmacological or genetic approaches, we reduce iron overload in AgRP neurons by central deferoxamine administration or transferrin receptor 1 (Tfrc) deletion, ameliorating diet-induced obesity and related metabolic dysfunction. Conversely, Tfrc-mediated iron overload in AgRP neurons leads to overeating and adiposity. Mechanistically, the reduction of iron overload in AgRP neurons inhibits AgRP neuron activity; improves insulin and leptin sensitivity; and inhibits iron-induced oxidative stress, endoplasmic reticulum stress, nuclear factor kappaB signaling, and suppression of cytokine signaling 3 expression. These results highlight the critical role of hypothalamic iron in obesity development and suggest targets for treating obesity and related metabolic disorders. |
