We have today a lot of different indications for a safe iron chelator, not only for Parkinson's, Alzheimer's, etc, but obesity is a new potential indication for me. As you know the obesity market is one of the hottest pharma markets today.
This paper below tells about this potential indication for an iron chelator:Iron overload in hypothalamic AgRP neurons contributes to obesity and related metabolic disorders
Yi Zhang 1, Liwei Chen 1, Ye Xuan 1, Lina Zhang 2, Wen Tian 3, Yangyang Zhu 4, Jinghui Wang 5, Xinyu Wang 6, Jin Qiu 7, Jian Yu 7, Mengyang Tang 4, Zhen He 1, Hong Zhang 1, Si Chen 1, Yun Shen 1, Siyi Wang 8, Rong Zhang 1, Lingyan Xu 9, Xinran Ma 10, Yunfei Liao 11, Cheng Hu 12AffiliationsDOI: 10.1016/j.celrep.2024.113900Free article
- PMID: 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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