Erythropoietin signaling: a novel regulator of white adipose tissue inflammation during diet-induced obesity.
Bottom Line: Using comprehensive in vivo and in vitro analyses in mice, EPO treatment inhibited WAT inflammation, normalized insulin sensitivity, and reduced glucose intolerance.Remarkably, and prior to any detectable changes in body weight or composition, EPO treatment reduced M1-like Mф and increased M2-like Mф in WAT, while decreasing inflammatory monocytes.These anti-inflammatory effects were found to be driven, at least in part, by direct EPO-R response in Mф via Stat3 activation, where EPO effects on M2 but not M1 Mф required interleukin-4 receptor/Stat6.
Affiliation: Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.Show MeSH
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Mentions: The effect of EPO administration on Mф population subtypes in WAT was examined. Using flow cytometry, EPO decreased MGL-1− and CD11c+ while increasing MGL-1+ Mф (Fig. 5A and B). qRT-PCR confirmed phenotypic Mф shift (Fig. 5C and D), showing that EPO reduced iNOS and Il-1β and increased Fizz-1, Ppar-γ, and Arg-1. Overall, EPO increased M2-like Mф and reduced M1-like Mф numbers, thus identifying and confirming its role in the regulation of not only Mф infiltration, but also local subtype polarization. Whether or not the conversion of M1- to M2-like Mф, as recently suggested (46), contributes to the observed EPO-mediated increase in MGL-1+ Mф remains unknown. Since M1/M2 nomenclature of Mф is based on in vitro studies, and may not represent in vivo Mф subtypes (17), we use the designation M1- and M2-like Mф to describe F4/80+MGL-1− and MGL-1+ cells, respectively.
Affiliation: Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.