title: 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.
authors.affiliation: Department of Medicine and Endocrinology, Aarhus University Hospital, Aarhus, Denmark. britt.christensen@ki.au.dk
authors.forename: Britt
authors.initials: B
authors.lastname: Christensen
authors.forename: Mikkel H
authors.initials: MH
authors.lastname: Vendelbo
authors.forename: Thomas
authors.initials: T
authors.lastname: Krusenstjerna-Hafstrøm
authors.forename: Michael
authors.initials: M
authors.lastname: Madsen
authors.forename: Steen B
authors.initials: SB
authors.lastname: Pedersen
authors.forename: Niels
authors.initials: N
authors.lastname: Jessen
authors.forename: Niels
authors.initials: N
authors.lastname: Møller
authors.forename: Jens Otto L
authors.initials: JO
authors.lastname: Jørgensen
mesh_terms: D015153:Blotting, Western; D002153:Calorimetry, Indirect; D018592:Cross-Over Studies; D004734:Energy Metabolism / Q000187:drug effects*; D004921:Erythropoietin / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005542:Forearm / Q000098:blood supply / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006728:Hormones / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D047495:PPAR gamma / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000494:pharmacology; D012039:Regional Blood Flow / Q000502:physiology; D012146:Rest / Q000502:physiology*; D055815:Young Adult
chemical_list: D005230:Fatty Acids, Nonesterified; D006728:Hormones; D007004:Hypoglycemic Agents; D007328:Insulin; D009124:Muscle Proteins; D047495:PPAR gamma; D011994:Recombinant Proteins; D004921:Erythropoietin; D005947:Glucose