1. Erythropoietin regulates energy metabolism through EPO-EpoR-RUNX1 axis.
- Author
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Yin W, Rajvanshi PK, Rogers HM, Yoshida T, Kopp JB, An X, Gassmann M, and Noguchi CT
- Subjects
- Animals, Male, Mice, Mice, Knockout, Mice, Inbred C57BL, Obesity metabolism, Obesity genetics, Muscle, Skeletal metabolism, Insulin Resistance, Lipogenesis genetics, Lipogenesis drug effects, Adipose Tissue, Brown metabolism, Signal Transduction drug effects, Erythropoietin metabolism, Erythropoietin genetics, Core Binding Factor Alpha 2 Subunit metabolism, Core Binding Factor Alpha 2 Subunit genetics, Energy Metabolism drug effects, Receptors, Erythropoietin metabolism, Receptors, Erythropoietin genetics, Adipose Tissue, White metabolism
- 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., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
- Published
- 2024
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