Mice with erythropoietin receptor restricted to erythroid tissue show a disproportionate increase in fat mass, glucose intolerance and insulin resistance, with a greater degree of obesity in female mice with age. Accompanying the increased erythropoiesis with erythropoietin treatment in mice is an improvement in glucose tolerance and a decrease in blood glucose level. Erythropoietin treatment also decreases fat mass, especially evident in obese male mice and obese ovariectomized female mice. In ovariectomized female mice, estrogen protection against diet induced obesity is greater than erythropoietin treatment and erythropoietin has no added effect when administered in combination with estrogen, suggesting that estrogen blunts the protective effect of erythropoietin against diet-induced obesity in mice. In mice, high-fat diet increases fat mass, body weight and inflammation of white adipose tissue. Insulin resistance is associated with white adipose tissue inflammation and infiltration of pro-inflammatory macrophages that give rise to crown-like structures in white adipose tissue of macrophages arranged around dead adipocytes. Erythropoietin treatment in diet-induced obese mice reduces white adipose tissue inflammation, macrophage infiltration and crown-like structures, and shifts the macrophage population toward anti-inflammatory macrophages. Glycogen synthase kinase 3, a serine/threonine kinase that phosphorylates and inhibits glycogen synthase, is negatively regulated by phosphorylation at serine 9. In diet-induced obese mice, glycogen synthase kinase 3 phosphorylation is decreased in white adipose tissue, including the macrophage containing stromal-vascular fraction. Inhibition of glycogen synthase kinase 3 in obese mice suppresses white adipose tissue inflammation and macrophage infiltration with a shift toward the anti-inflammatory macrophage subtype. Reduction in inflammation and promotion of an anti-inflammatory phenotype in white adipose tissue likely contribute to the associated improvement in insulin resistance associated with erythropoietin treatment and with glycogen synthase kinase 3 inhibition in diet-induced obese mice.
| 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 |
| 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 |
| 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 |
Showing the most recent 10 out of 20 publications
