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: To investigate the role of endogenous EPO/EPO-R signaling in regulating glucose metabolism, we compared WT with ∆EpoR mice after 12 weeks of HFD feeding. ∆EpoR mice showed higher insulin resistance, glucose intolerance, fasting blood glucose, and serum insulin (Fig. 8A–D). ∆EpoR mice maintained high insulin resistance after 2 weeks of EPO administration (Fig. 8E and F), and there was no change in the area under the curve and no significant difference in glucose intolerance after EPO treatment (Fig. 8G). Not surprisingly, Mф infiltration and subtype composition in WAT of ∆EpoR mice remained similar after EPO administration (Fig. 8H).
Affiliation: Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.