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 during obesity-induced WAT inflammation, we used DIO in ∆EpoR mice (39). The absence of EPO-R expression in ∆EpoR WAT (adipocytes and SVF) and Mф were confirmed (Figs. 3B and 7A). ∆EpoR mice maintained on normal chow become obese and glucose intolerant as they age (36). Baseline measurements prior to the onset of HFD feeding showed ∆EpoR mice (6–8 weeks old) to have slightly higher body weight and fat mass compared with age-matched WT controls (Fig. 7B). However, after 12 weeks of HFD feeding, there was no significant difference in final body weight or fat mass between ∆EpoR and their age-matched WT controls (Fig. 7B).
Affiliation: Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.