Abstract
Background: Dyslipidemia is commonly observed in various kidney diseases, renal specific secreted erythropoietin (EPO) may participate in this process. However, how this process is regulated has remained mostly elusive. Method: The dyslipidemia was evaluated in chronic kidney disease and ischemia kidney injury animal model. Primary cultured adipocytes was used to investigate the lipolytic effect of EPO. Lipidemia was evaluated in EPO treated animal. Blood samples from cardiac surgery-induced kidney injury were collected to assess correlationship between EPO and lipidemia. Findings: We found a decrease in secreted EPO, led to hypertriglyceridemia in chronic kidney disease (CKD) mice. In contrast, in ischemic kidney animal model, increased EPO triggered by hypoxia signaling activation, was accompanied by decreased triglyceride (TG) in plasma. Mechanistically, circulating EPO modulates JAK2-STAT5 signaling, which in turn enhances lipolysis in peripheral adipose tissue and contributes to dysregulated lipidemia in serum. Delivering of recombinant EPO into both normal and CKD mice suppressed plasma TG by accelerating lipolysis in adipose tissue. In a cohort of patients diagnosed with acute kidney injury after cardiopulmonary bypass surgery, the decreased TG and cholesterol negatively correlated with increased EPO in the serum. Interpretation: This study identifies that renal secreted EPO controls lipidemia in kidney disease, providing a new mechanism underlying dyslipidemia in chronic kidney disease. Circulating EPO stimulates lipolysis by targeting JAK2-STATA5 signaling in peripheral adipose tissue, providing new therapeutic target for dyslipidemia treatment. Funding Statement: This work was supported by grants from the National Natural Science Foundation of China (Nos. 81700640, 81970608). Declaration of Interests: The authors declare that there is no duality of interest associated with this manuscript. Ethics Approval Statement: All clinical study were approved by the Medical Ethics Committee of Nanfang Hospital (Guangzhou, China). The participants in the study provided written informed consent. All animal experiments were approved by the Institutional Animal Care Committee of Nanfang Hospital.
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