An Iron Refractory Phenotype in Obese Adipose Tissue Macrophages Leads to Adipocyte Iron Overload.
Magdalene K AmekaWilliam N BeaversCiara M ShaverLorraine B WareVern Eric KerchbergerKelly Q SchoenfeltLili SunTatsuki KoyamaEric P SkaarLev BeckerAlyssa H HastyPublished in: International journal of molecular sciences (2022)
Adipocyte iron overload is a maladaptation associated with obesity and insulin resistance. The objective of the current study was to determine whether and how adipose tissue macrophages (ATMs) regulate adipocyte iron concentrations and whether this is impacted by obesity. Using bone marrow-derived macrophages (BMDMs) polarized to M0, M1, M2, or metabolically activated (MMe) phenotypes, we showed that MMe BMDMs and ATMs from obese mice have reduced expression of several iron-related proteins. Furthermore, the bioenergetic response to iron in obese ATMs was hampered. ATMs from iron-injected lean mice increased their glycolytic and respiratory capacities, thus maintaining metabolic flexibility, while ATMs from obese mice did not. Using an isotope-based system, we found that iron exchange between BMDMs and adipocytes was regulated by macrophage phenotype. At the end of the co-culture, MMe macrophages transferred and received more iron from adipocytes than M0, M1, and M2 macrophages. This culminated in a decrease in total iron in MMe macrophages and an increase in total iron in adipocytes compared with M2 macrophages. Taken together, in the MMe condition, the redistribution of iron is biased toward macrophage iron deficiency and simultaneous adipocyte iron overload. These data suggest that obesity changes the communication of iron between adipocytes and macrophages and that rectifying this iron communication channel may be a novel therapeutic target to alleviate insulin resistance.
Keyphrases
- adipose tissue
- insulin resistance
- iron deficiency
- high fat diet induced
- metabolic syndrome
- high fat diet
- type diabetes
- weight loss
- skeletal muscle
- polycystic ovary syndrome
- poor prognosis
- mass spectrometry
- mesenchymal stem cells
- weight gain
- machine learning
- high resolution
- artificial intelligence
- obese patients
- body mass index
- bone mineral density
- bone marrow