Yin Weiqin, Noguchi Constance T
Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
Cells. 2025 Feb 14;14(4):280. doi: 10.3390/cells14040280.
Erythropoietin (EPO) is a key regulator of erythrocyte production, promoting erythroid progenitor cell survival, division, and differentiation in the fetal liver and adult bone marrow. Mice lacking EPO or its receptor (EPOR) die in utero due to severe anemia. Beyond hematopoiesis, EPO influences non-hematopoietic tissues, including glucose and fat metabolism in adipose tissue, skeletal muscle, and the liver. EPO is used to treat anemia associated with chronic kidney disease clinically and plays a role in maintaining metabolic homeostasis and regulating fat mass. EPO enhances lipolysis while inhibiting lipogenic gene expression in white adipose tissue, brown adipose tissue, skeletal muscle, and the liver, acting through the EPO-EPOR-RUNX1 axis. The non-erythroid EPOR agonist ARA290 also improves diet-induced obesity and glucose tolerance providing evidence for EPO regulation of fat metabolism independent of EPO stimulated erythropoiesis. Therefore, in addition to the primary role of EPO to stimulate erythropoiesis, EPO contributes significantly to EPOR-dependent whole-body metabolic response.
促红细胞生成素（EPO）是红细胞生成的关键调节因子，可促进胎儿肝脏和成人骨髓中红系祖细胞的存活、分裂和分化。缺乏EPO或其受体（EPOR）的小鼠会因严重贫血在子宫内死亡。除了造血作用外，EPO还会影响非造血组织，包括脂肪组织、骨骼肌和肝脏中的葡萄糖和脂肪代谢。临床上，EPO用于治疗与慢性肾病相关的贫血，并在维持代谢稳态和调节脂肪量方面发挥作用。EPO通过EPO-EPOR-RUNX1轴发挥作用，增强白色脂肪组织、棕色脂肪组织、骨骼肌和肝脏中的脂肪分解，同时抑制脂肪生成基因的表达。非红系EPOR激动剂ARA290也能改善饮食诱导的肥胖和葡萄糖耐量，为EPO独立于EPO刺激的红细胞生成对脂肪代谢的调节提供了证据。因此，除了EPO刺激红细胞生成的主要作用外，EPO对依赖EPOR的全身代谢反应也有显著贡献。
