Erythropoietin, a Novel Versatile Player Regulating Energy Metabolism beyond the Erythroid System

Abstract

Erythropoietin (EPO), the required cytokine for promoting the proliferation and differentiation of erythroid cells to stimulate erythropoiesis, has been reported to act as a pleiotropic cytokine beyond hematopoietic system. The various activities of EPO are determined by the widespread distribution of its cell surface EPO receptor (EpoR) in multiple tissues including endothelial, neural, myoblasts, adipocytes and other cell types. EPO activity has been linked to angiogenesis, neuroprotection, cardioprotection, stress protection, anti-inflammation and especially the energy metabolism regulation that is recently revealed. The investigations of EPO activity in animals and the expression analysis of EpoR provide more insights on the potential of EPO in regulating energy metabolism and homeostasis. The findings of crosstalk between EPO and some important energy sensors and the regulation of EPO in the cellular respiration and mitochondrial function further provide molecular mechanisms for EPO activity in metabolic activity regulation. In this review, we will summarize the roles of EPO in energy metabolism regulation and the activity of EPO in tissues that are tightly associated with energy metabolism. We will also discuss the effects of EPO in regulating oxidative metabolism and mitochondrial function, the interactions between EPO and important energy regulation factors, and the protective role of EPO from stresses that are related to metabolism, providing a brief overview of previously less appreciated EPO biological function in energy metabolism and homeostasis.

Chronic erythropoietin treatment improves diet-induced glucose intolerance in rats

“…Initial blood glucose levels may thus be critical in the acute effect of EPO, consistent with the study reporting that hyperglycemia is necessary for stimulation of EPO-induced glucose uptake in adipocytes (Mikolás et al 2012). As we have also shown that rat soleus muscle did not express EPOR, AKT activation in our model is likely to be indirect via a still unknown mechanism (Wang et al 2014). In human, acute i.v.…”

Tubular Vascular Endothelial Growth Factor-A, Erythropoietin, and Medullary Vessels

“…7,8 In addition to endocrine stimulation of erythropoiesis, EPO promotes endothelial cell survival and proliferation in vitro and in vivo. 9,10 Like VEGF tub mice, Epo transgenic mice develop hematocrit of approximately 80%, have normal BP and renal function, and have no evidence of cardiovascular disease or thrombotic events. This remarkable adaptation was found to be mediated by increased endothelial NOS (eNOS) expression and nitric oxide (NO) levels.…”

Role of alternative phosphorylation and O-glycosylation of erythropoietinreceptor in modulating its function: an in silico study

“…Erythropoietin exerts multiple effects in different organs and tissues (Wang et al, 2014). In hematopoietic tissues, EPO is involved in the cell cycle progression, proliferation, and differentiation of erythroid progenitor cells.…”

“…Early studies on EPO-R showed that this receptor is only expressed in cells of the erythroid lineage, emphasizing that the action of EPO is limited to red blood cell manufacturing, while further studies divulged the wide expression of the EPO-R, increasing the likelihood of extra-hematopoietic effect of EPO (Wang et al, 2014). The detection of EPO-R mRNA in the brain, heart, retinal, skeletal, muscle, and kidney cells makes it a promising target to study its untold functions (Morishita et al, 1997;Wu et al, 1999;Noguchi et al, 2008;Hu et al, 2013).…”