Chronic erythropoietin treatment improves diet-induced glucose intolerance in rats

Abstract

Erythropoietin (EPO) ameliorates glucose metabolism through mechanisms not fully understood. In this study, we investigated the effect of EPO on glucose metabolism and insulin signaling in skeletal muscle. A 2-week EPO treatment of rats fed with a high-fat diet (HFD) improved fasting glucose levels and glucose tolerance, without altering total body weight or retroperitoneal fat mass. Concomitantly, EPO partially rescued insulin-stimulated AKT activation, reduced markers of oxidative stress, and restored heat-shock protein 72 expression in soleus muscles from HFD-fed rats. Incubation of skeletal muscle cell cultures with EPO failed to induce AKT phosphorylation and had no effect on glucose uptake or glycogen synthesis. We found that the EPO receptor gene was expressed in myotubes, but was undetectable in soleus. Together, our results indicate that EPO treatment improves glucose tolerance but does not directly activate the phosphorylation of AKT in muscle cells. We propose that the reduced systemic inflammation or oxidative stress that we observed after treatment with EPO could contribute to the improvement of whole-body glucose metabolism.

Erythropoietin (EPO) ameliorates obesity and glucose homeostasis by promoting thermogenesis and endocrine function of classical brown adipose tissue (BAT) in diet-induced obese mice

“…Furthermore, we showed that EPO reduced blood glucose levels during an intraperitoneal glucose tolerance test (IPGTT) without changing serum insulin levels in obese mice (Fig 3A and 3B). This effect of EPO in improving glucose tolerance is also consistent with previous studies [2,3,8,10,11,14]. Here, we provide new evidence that classical brown adipose tissue (BAT) plays an important role in how EPO alleviates obesity and glucose homeostasis in mice.…”

Combination of exercise training and erythropoietin prevents cancer-induced muscle alterations

“…In this regard, in the skeletal muscle of EPO-deficient mice the expression of genes related to mitochondrial function is low, while genes involved in proteolysis and hypoxia are overexpressed, suggesting that EPO plays a relevant role in muscle tissue [ 9 ]. Consistently, EPO administration to rats rapidly stimulates glucose metabolism and muscle anabolism [ 10 ]. Recently, EPO and EPO-R have been involved in muscle regeneration.…”

Latest advances in STAT signaling and function in adipocytes

“…Erythropoietin (EPO) has been reported to have both anti-obesity and anti-diabetic effects in AT, but the mechanisms by which EPO confers these effects are unclear [32][33][34]. In a recent study, high-fat diet (HFD)-fed diet-induced obese (DIO) mice injected with a non-erythropoietic EPO-derived peptide had reduced epididymal and inguinal white adipose tissue masses (eWAT and iWAT), improved glucose tolerance and insulin sensitivity, and enhanced oxygen consumption compared to controls [34].…”