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Erythropoietin signaling: A novel regulator of white adipose tissue inflammation during diet-induced obesity

Thursday, October 11, 2012 — Poster Session IV

2:00 p.m. – 4:00 p.m.

Natcher Conference Center, Building 45



* FARE Award Winner


  • M Al-Naeeli


Obesity-induced white adipose tissue (WAT) inflammation and insulin resistance are associated with macrophage infiltration and phenotypic shift from “anti-inflammatory” M2-like to predominantly “pro-inflammatory” M1-like cells. Erythropoietin (EPO), discovered for its indispensable role during erythropoiesis, is a glycoprotein hormone whose biological activities extend to non-erythroid tissues and include anti-apoptotic and anti-inflammatory effects. We observed high levels of EPO receptor (EPO-R) expression in WAT and investigated EPO involvement in the regulation of obesity-induced inflammation and insulin resistance. Using the murine model of diet-induced obesity EPO treatment was found to inhibit WAT inflammation, normalize insulin sensitivity and reduce glucose intolerance. Remarkably, and prior to any detectable changes in body weight or composition, EPO treatment reduced M1-like macrophages and increased M2-like macrophages in WAT, while decreasing Ly6ChiCCR2+ inflammatory monocytes in the circulation. Obese mice lacking EPO-R expression in WAT exhibited more metabolic impairment and elevated WAT inflammation, with higher circulating inflammatory monocytes, increased M1-like and reduced M2-like macrophages, than wild type controls confirming an anti-inflammatory role for endogenous EPO. Collectively, our findings identify EPO/EPO-R signaling as a novel regulator of obesity-induced WAT inflammation, and extend its non-erythroid activity to encompass effects on both the infiltration and subset composition of macrophages in the WAT.

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