Erythropoietin regulates energy metabolism through EPO-EpoR-RUNX1 axis

Weiqin Yin, Praveen Kumar Rajvanshi, Heather M. Rogers, Teruhiko Yoshida, Jeffrey B. Kopp, Xiuli An, Max Gassmann and Constance T. Noguchi ()
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Weiqin Yin: National Institute of Diabetes and Digestive and Kidney Diseases, NIH
Praveen Kumar Rajvanshi: National Institute of Diabetes and Digestive and Kidney Diseases, NIH
Heather M. Rogers: National Institute of Diabetes and Digestive and Kidney Diseases, NIH
Teruhiko Yoshida: National Institute of Diabetes and Digestive and Kidney Diseases, NIH
Jeffrey B. Kopp: National Institute of Diabetes and Digestive and Kidney Diseases, NIH
Xiuli An: New York Blood Center
Max Gassmann: University of Zurich
Constance T. Noguchi: National Institute of Diabetes and Digestive and Kidney Diseases, NIH

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Erythropoietin (EPO) plays a key role in energy metabolism, with EPO receptor (EpoR) expression in white adipose tissue (WAT) mediating its metabolic activity. Here, we show that male mice lacking EpoR in adipose tissue exhibit increased fat mass and susceptibility to diet-induced obesity. Our findings indicate that EpoR is present in WAT, brown adipose tissue, and skeletal muscle. Elevated EPO in male mice improves glucose tolerance and insulin sensitivity while reducing expression of lipogenic-associated genes in WAT, which is linked to an increase in transcription factor RUNX1 that directly inhibits lipogenic genes expression. EPO treatment in wild-type male mice decreases fat mass and lipogenic gene expression and increase in RUNX1 protein in adipose tissue which is not observed in adipose tissue EpoR ablation mice. EPO treatment decreases WAT ubiquitin ligase FBXW7 expression and increases RUNX1 stability, providing evidence that EPO regulates energy metabolism in male mice through the EPO-EpoR-RUNX1 axis.

Date: 2024
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DOI: 10.1038/s41467-024-52352-z

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