Kidney-secreted Erythropoietin Lowers Lipidemia Via Activating JAK2-STAT5 Signaling in Adipose Tissue

Overview

Journal EBioMedicine

Specialty Biomedical Engineering

Date 2019 Nov 20

PMID 31740386

Citations 8

Authors

Jinxiang Li

Minliang Yang

Zhuo Yu

Jianwei Tian

Songlin Du

Hanying Ding

Affiliations

Soon will be listed here.

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 remains elusive.

Method: Dyslipidemia was evaluated in chronic kidney disease and ischemia kidney injury animal model. Primary cultured adipocytes were harvested to investigate the lipid metabolic effect of EPO. Lipidemia was evaluated in EPO treated animals. Blood samples from cardiac surgery-induced kidney injury patient were collected to assess correlationship between EPO and lipidemia.

Findings: We found a decrease in secreted EPO and hypertriglyceridemia in chronic kidney disease (CKD) mice. In contrast, in renal ischemia animal model, increased EPO triggered by hypoxia signaling activation, was accompanied by decreased triglyceride (TG) in serum. Mechanistically, circulating EPO modulated JAK2-STAT5 signaling, which in turn enhanced lipid catabolism in peripheral adipose tissue and contributed to dysregulated lipidemia. Delivering of recombinant EPO into both wild type and CKD mice suppressed TG in serum by accelerating lipid catabolism 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 serum.

Interpretation: This study depicted a new mechanism by which renal secreted EPO controlled lipidemia in kidney diseases including chronic kidney disease. Circulating EPO stimulated lipid catabolism by targeting JAK2-STATA5 signaling in peripheral adipose tissue, providing new therapeutic target for dyslipidemia treatment.

Funding: This work was supported by grants from the National Natural Science Foundation of China (Nos. 81700640 and 81970608).

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