Remission of iron overload in adipose tissue of obese mice by fatty acid-modified polyoxovanadates

Iron overload has been evidenced to contribute to obesity-associated metabolic disorders, including insulin resistance. Strategies to reduce iron levels might help manage the metabolic complications associated with obesity. Here, it is demonstrated that the specific accumulation of oleic acid-modified polyoxovanadates (OPOVs) in adipose tissue leads to the reduction of iron concentrations in adipocytes in mice fed with a high-fat diet (HFD). Conjugation of oleic acids to polyoxovanadates enables tissue-specific depletion of iron from white adipose tissue (WAT) by OPOVs, protecting mice from HFD-induced obesity and obesity-associated metabolic deteriorations. Glucose tolerance and insulin sensitivity are improved in OPOV-treated mice, which demonstrates that the OPOV-induced iron depletion can reverse the metabolic degeneration caused by HFD-induced obesity. Furthermore, a decrease in expression of the marker genes of iron overload suggests the participation of OPOVs in maintaining iron homeostasis and a potential medical application of vanadium clusters in targeting the iron overload caused by obesity. These findings underscore the potential of vanadate-based clusters tailored to address the complex interplay between iron metabolism and metabolic health. Graphical abstract