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Deferoxamine ameliorates adipocyte dysfunction by modulating iron metabolism in ob/ob mice
OBJECTIVE: The mechanisms underlying obesity and anti-obesity processes have garnered remarkable attention as potential therapeutic targets for obesity-associated metabolic syndromes. Our prior work has shown the healing efficacy of iron reduction therapies for hepatic steatosis in a rodent model of...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Bioscientifica Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911700/ https://www.ncbi.nlm.nih.gov/pubmed/29678877 http://dx.doi.org/10.1530/EC-18-0054 |
Sumario: | OBJECTIVE: The mechanisms underlying obesity and anti-obesity processes have garnered remarkable attention as potential therapeutic targets for obesity-associated metabolic syndromes. Our prior work has shown the healing efficacy of iron reduction therapies for hepatic steatosis in a rodent model of diabetes and obesity. In this study, we investigated how iron depletion by deferoxamine (DFO) affected adipocyte dysfunction in the epididymal adipose tissues of ob/ob mice. METHODS: Male ob/ob mice were assigned to either a vehicle-treated or DFO-treated group. DFO (100 mg/kg body weight) was injected intraperitoneally for 15 days. RESULTS: We confirmed that iron deposits were statistically increased in the epididymal fat pad of 26-week-old ob/ob mice compared with wild-type (WT) mice. DFO significantly improved vital parameters of adipose tissue biology by reducing reactive oxygen species and inflammatory marker (TNFα, IL-2, IL-6, and Hepcidin) secretion, by increasing the levels of antioxidant enzymes, hypoxia-inducible factor-1α (HIF-1α) and HIF-1α-targeted proteins, and by altering adipocytic iron-, glucose- and lipid-associated metabolism proteins. Meanwhile, hypertrophic adipocytes were decreased in size, and insulin signaling pathway-related proteins were also activated after 15 days of DFO treatment. CONCLUSIONS: These findings suggest that dysfunctional iron homeostasis contributes to the pathophysiology of obesity and insulin resistance in adipose tissues of ob/ob mice. Further investigation is required to develop safe iron chelators as effective treatment strategies against obesity, with potential for rapid clinical application. |
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