239-LB: Erythropoietin Alters Fat Mass and Gut Microbial Composition

Abstract

Erythropoietin is an essential hormone for promoting erythropoiesis. Erythropoietin also stimulates angiogenesis, affects fat metabolism and can promote survival in cells expressing erythropoietin receptor. Here, we found that erythropoietin reduces fat mass, decreasing epididymis fat pad mass and subcutaneous fat pad mass of Tg6 male mice that express high transgenic erythropoietin. However, how erythropoietin activity in the gut improves fat mass and glucose metabolism is not known. Tg6 male mice have increased microvilli height and intestine length. High erythropoietin changes the gut microbiota by altering β-diversity that includes increasing the abundance of Bifidobacterium and reducing the Lactobacillaceae in Tg6 male mice. EPO decreased lactate dehydrogenase (LDHa) expression and reduces lactate production from intestinal endothelial cells that affects the gut microbiota components. Accompanying the altered microbiome are increased intestinal short-chain fatty acid levels that can affect fat metabolism. Transplantation of fecal pellet from Tg6 male mice into antibiotic treated male wild type mice reduces fat mass and mimics the lean phenotype of Tg6 mice. Conversely, transplanting feces from WT mice into Tg6 mice resulted in increased fat mass in Tg6 mice. Wild type male mice treated with erythropoietin show improved glucose tolerance and also exhibit increased intestine length and changes in the gut microbiota with increase in Bifidobacterium and decrease in Lactobacillaceae, analogous to changes in Tg6 male mice. Our results on erythropoietin activity in the gut to change gut morphology and remodel the gut microbiome provide a new mechanism by which EPO affects fat metabolism. Key words: EPO; EPOR; gut microbial composition; fat mass Disclosure W. Yin: None. H. Rogers: None. X. An: None. M. Gassmann: None. C. T. Noguchi: None.