218-LB: Age, Sex, and Fat Mass Affects Erythropoietin Metabolic Response in Mice

Abstract

Erythropoietin (EPO) is required for erythrocyte production. However, EPO receptor (EpoR) extends beyond erythroid tissue and ΔEpoR mice with EpoR restricted to hematopoietic tissue show an increase in fat mass. At 3 months of age, ΔEpoR mice show no difference in body weight compared with wild type (WT, C57BL/6) mice. By 6 months of age, male body weights of ΔEpoR mice are greater than WT mice, and at 8+ months body weights of male and female ΔEpoR mice are greater than their WT counterparts. To assess EPO activity on glucose homeostasis and fat mass, mice were fed a high fat diet (HFD, 60% kCal fat) and treated with EPO (3000U/kg 3X per week) or saline for 3 weeks at age 3, 6, and 8+ months. EPO increased hematocrit in all mice. EPO treatment in male WT mice reduces weight and fat mass at 6 and 8+ months of age, when their fat mass is 35% or greater with saline treatment. Female WT mice treated with EPO do not show significantly less weight or fat mass at any age. EPO treatment does not affect weight or fat mass in ΔEpoR mice. With HFD feeding and EPO treatment in 3 month old mice, body weights are not different between WT and ΔEpoR mice although fat mass is significantly higher in ΔEpoR mice. At 6 months, body weight and fat mass in males are greater in ΔEpoR than WT, while ΔEpoR females show no difference in body weight but significantly more fat mass compared with WT females. In the older mice (8+ months old), both sexes of ΔEpoR mice are significantly heavier and fatter than WT mice. EPO treatment improves glucose tolerance in female ΔEpoR mice at 3 and 6 months but not at 8+months, whereas male ΔEpoR mice only showed improvement at 3 months, not at 6 and 8+months. In male and female WT mice, EPO improves glucose metabolism at 3 and 6 months, and to a lesser extent at 8+ months with greater improvement in mice with <35% fat mass. These data show that EPO regulates metabolism in a sex and age dependent manner mediated via EpoR expression in non-hematopoietic tissue and is influenced by level of fat mass. Disclosure H. Rogers: None. C. T. Noguchi: None.