Erythropoietin, a glycoprotein hormone indispensable for erythropoiesis, has biological activities that extend to non-erythroid tissues including anti-apoptotic and anti-inflammatory effects. Mice with erythropoietin receptor restricted to erythroid tissue show an abnormal increase in weight gain, are glucose intolerant and develop insulin resistance. Obesity-induced white adipose tissue inflammation and insulin resistance are associated with macrophage infiltration and phenotypic shift from anti-inflammatory M2-like to predominantly pro-inflammatory M1-like cells. We use in vivo and in vitro analysis of a mouse model of diet induced obesity and found that erythropoietin treatment inhibited inflammation of white adipose tissue, normalized insulin sensitivity and reduced glucose intolerance. Prior to any detectable changes in body weight or composition, erythropoietin treatment reduced M1-like macrophages and increased M2-like macrophages in white adipose tissue. Erythropoietin receptor expression in macrophages provided an erythropoietin response resulting in STAT3 activation and erythropoietin effects on M2 but not M1-like macrophages required IL-4 receptor and STAT6 activation. Mice with erythropoietin receptor restricted to erythroid tissue did not exhibit this anti-inflammatory response with erythropoietin treatment. In vitro studies confirmed the requirement for erythropoietin receptor for a macrophage response to erythropoietin. These findings identify erythropoietin signaling as a novel regulator of white adipose tissue inflammation.
| Wang, Li; Wang, Yuan; Zhang, Chao et al. (2018) Inhibiting Glycogen Synthase Kinase 3 Reverses Obesity-Induced White Adipose Tissue Inflammation by Regulating Apoptosis Inhibitor of Macrophage/CD5L-Mediated Macrophage Migration. Arterioscler Thromb Vasc Biol : |
| Dey, Soumyadeep; Noguchi, Constance T (2017) Erythropoietin and Hypothalamic-Pituitary Axis. Vitam Horm 105:101-120 |
| Zhang, Yuanyuan; Rogers, Heather M; Zhang, Xiaojie et al. (2017) Sex difference in mouse metabolic response to erythropoietin. FASEB J 31:2661-2673 |
| Dey, Soumyadeep; Li, Xiaoxia; Teng, Ruifeng et al. (2016) Erythropoietin regulates POMC expression via STAT3 and potentiates leptin response. J Mol Endocrinol 56:55-67 |
| Reinhardt, Martin; Dey, Soumyadeep; Tom Noguchi, Constance et al. (2016) Non-hematopoietic effects of endogenous erythropoietin on lean mass and body weight regulation. Obesity (Silver Spring) 24:1530-6 |
| Dey, Soumyadeep; Scullen, Tyler; Noguchi, Constance Tom (2015) Erythropoietin negatively regulates pituitary ACTH secretion. Brain Res 1608:14-20 |
| Piknova, Barbora; Park, Ji Won; Swanson, Kathryn M et al. (2015) Skeletal muscle as an endogenous nitrate reservoir. Nitric Oxide 47:10-16 |
| Alnaeeli, Mawadda; Raaka, Bruce M; Gavrilova, Oksana et al. (2014) Erythropoietin signaling: a novel regulator of white adipose tissue inflammation during diet-induced obesity. Diabetes 63:2415-31 |
| Cokic, Bojana B Beleslin; Cokic, Vladan P; Suresh, Sukanya et al. (2014) Nitric oxide and hypoxia stimulate erythropoietin receptor via MAPK kinase in endothelial cells. Microvasc Res 92:34-40 |
| Zhang, Yuanyuan; Wang, Li; Dey, Soumyadeep et al. (2014) Erythropoietin action in stress response, tissue maintenance and metabolism. Int J Mol Sci 15:10296-333 |
Showing the most recent 10 out of 20 publications
