Iron overload in hypothalamic AgRP neurons contributes to obesity and related metabolic disorders.
Cell Rep
; 43(3): 113900, 2024 Mar 26.
Article
en En
| MEDLINE
| ID: mdl-38460132
ABSTRACT
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 κB 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.
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Bases de datos:
MEDLINE
Asunto principal:
Sobrecarga de Hierro
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Enfermedades Metabólicas
Idioma:
En
Revista:
Cell Rep
Año:
2024
Tipo del documento:
Article
País de afiliación:
China