Erythropoietin administration acutely stimulates resting energy expenditure in healthy young men

Abstract

Treatment with recombinant human erythropoietin (rHuEpo) improves insulin sensitivity in patients with end-stage renal disease, and animal studies indicate that Epo increases fat oxidation. However, the metabolic effects of rHuEpo have never been experimentally studied in healthy humans. The aim was to investigate the effects of an acute rHuEpo bolus on substrate metabolism and insulin sensitivity in healthy young men. Ten healthy young men were studied in a single-blinded, randomized crossover design with a 2-wk washout period receiving 400 IU/kg rHuEpo or placebo. Substrate metabolism was evaluated by indirect calorimetry and tracer infusions, and insulin sensitivity by a hyperinsulinemic euglycemic clamp; and PCR and Western blotting measured protein expression and content, respectively. Resting energy expenditure (REE) increased significantly after rHuEpo [basal: 1,863.3 ± 67.2 (kcal/day) (placebo) vs. 2,041.6 ± 81.2 (rHuEpo), P < 0.001; clamp: 1,903.9 ± 68.3 (placebo) vs. 2,015.7 ± 114.4 (rHuEpo), P = 0.03], but the increase could not be explained by changes in mRNA levels of uncoupling protein 2 or 3. Fat oxidation in the basal state tended to be higher after rHuEpo but could not be explained by changes in mRNA levels of CPT1 and PPARα or AMPK and ACC protein phosphorylation. Insulin-stimulated glucose disposal, glucose metabolism, and whole body and forearm protein metabolism did not change significantly in response to rHuEpo. In conclusion, a single injection of rHuEpo acutely increases REE in healthy human subjects. This calorigenic effect is not accompanied by distinct alterations in the pattern of substrate metabolism or insulin sensitivity.

Growth Hormone and Insulin Signaling in Acromegaly: Impact of Surgery Versus Somatostatin Analog Treatment

“…In support of this, adipose tissue specific deletion of Epo-R in mice did not significantly alter whole-body energy expenditure or RQ values [15]. Resting energy expenditure significantly increased in the current studies, and fat oxidation tended to be increased in relation to rHuEpo treatment [6,7]. The effect of Epo on POMC was not Fig.…”

“…Studies in end-stage renal disease (ERSD) patients show that serum levels of triglycerides, total cholesterol, and LDL decrease to normal levels after Epo treatment [3][4][5], but acute administration of rHuEpo in healthy subjects do not significantly affect lipid levels, although a tendency to increased free fatty acid (FFA) levels have been observed [6]. However, prolonged treatment to healthy humans with an erythropoiesis-stimulating agent (ESA) significantly increases serum FFA levels and hepatic lipid content [7].…”

“…One explanation could be an increase in resting energy expenditure including fat oxidation [2], but only the former has been documented in healthy human subjects [6,7]. As regards direct peripheral actions of Epo, there is no evidence to support such effects in human skeletal muscle [12,13].…”

Effects of an 8-weeks erythropoietin treatment on mitochondrial and whole body fat oxidation capacity during exercise in healthy males

“…Animal and human studies evaluating the metabolic effects of erythropoietin mainly show increases in RER and protection against high-fat-diet-induced obesity by an increased muscle fat oxidation (Christensen, Lundby, et al, 2012;Christensen et al, 2013;Hojman et al, 2009;Meng, Zhu, Bi, Yang, & Wang, 2013). In young healthy males, Christensen, Vendelbo, et al (2012) demonstrated that RER was higher after an acute high dose (400 IU · kg −1 ) infusion of recombinant erythropoietin, together with a tendency for an increased basal whole body fat oxidation. However, specific energy sensing muscle key proteins regulating influx of fatty acids to the mitochondria, such as AMP-activated protein kinase and Acetyl CoA carboxylase were not altered by the treatment.…”

Influência da administração de eritropoietina humana recombinante sobre o desempenho físico: estudo de revisão

“…Mikolás et al 64 observaram também perda de peso em animais tratados com rHuEPO. Além disto, Christensen et al 65 , após investigarem os efeitos da administraç ão aguda de rHuEPO sobre o metabolismo da sensibilidade à insulina em indivíduos jovens saudáveis, observaram aumento do gasto energético em resposta à administraç ão de uma única dose do hormônio (400 UI/kg). Adicionalmente, já foi relatado que a rHuEPO está relacionada com a prevenç ão de lesão renal aguda, em um modelo experimental de treinamento físico de alta intensidade, em virtude de seu efeito antiapoptótico 66 .…”