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Erythropoietin, Versatile Player

 EPO activity has been linked to angiogenesis, neuroprotection, cardioprotection, stress protection, anti-inflammation and especially the energy metabolism regulation that is recently revealed.

The primary physiological function of EPO system is to stimulate erythroid progenitor cell production to provide adequate red blood cells and oxygen delivery. However, emerging evidences revealed previously less realized roles of EPO and EpoR(receptor) signaling beyond hematopoietic system. For example, EPO stimulated angiogenesis via endothelial cells in cardiovascular system contributes to cardioprotection to ischemic injury. EPO also provides neuroprotection during ischemic/hypoxic stress or disease via stress induced EPO production and EpoR expression in the brain to exert the antiapoptotic, oxygen delivery and anti-inflammatory effects. 
The protective function and the wound healing and repair role of EPO in skeletal muscle during ischemic/injury were also demonstrated.
These pleiotropic activities of EPO in non-erythroid system strongly suggest therapeutic potential of EPO beyond its traditionally primary clinical application in hematopoietic system. More interestingly, recently published data confirm the tight link between EPO/EpoR signaling and energy metabolism and homeostasis. 

EPO administration could protects us from diet induced obesity, promotes energy expenditure, reduces fat mass accumulation and improves glucose intolerance and insulin resistance. The loss of EPO activity in non-hematopoietic system leads to glucose intolerant and insulin resistant with the development of obesity. EPO activity is also demonstrated to play a role in central regulation of appetite. The crosstalk between EPO and other important energy sensors including PGC-1α, Sirt1 and AMPK further provides a mechanism for EPO regulating energy homeostasis. Although these novel findings highlight the possible therapeutic potential of EPO in non-hematopoietic diseases. Further studies are required to uncover the detailed mechanism by which EPO regulates central control of energy homeostasis and energy metabolism in multiple tissues.