Erythropoietin treatment enhances muscle mitochondrial capacity in humans

Ulla Plenge; Bo Belhage; Amelia Guadalupe-Grau; Peter Riis Andersen; Carsten Lundby; Flemming Dela; Nis Stride; Frank Christian Pott; Jørn Wulff Helge; Robert Boushel

doi:10.3389/fphys.2012.00050

Erythropoietin treatment enhances muscle mitochondrial capacity in humans

Ulla Plenge, Bo Belhage, Amelia Guadalupe-Grau, Peter Riis Andersen, Carsten Lundby, Flemming Dela, Nis Stride, Frank Christian Pott, Jørn Wulff Helge, Robert Boushel

28 Citations (Scopus)

Abstract

Erythropoietin (Epo) treatment has been shown to induce mitochondrial biogenesis in cardiac muscle along with enhanced mitochondrial capacity in mice. We hypothesized that recombinant human Epo (rhEpo) treatment enhances skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over 8 weeks with oral iron (100 mg) supplementation taken daily. Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis before and after rhEpo treatment. OXPHOS was determined with the mitochondrial complex I substrates malate, glutamate, pyruvate, and complex II substrate succinate in the presence of saturating ADP concentrations, while maximal electron transport capacity (ETS) was assessed by addition of an uncoupler. rhEpo treatment increased OXPHOS (from 92 ± 5 to 113 ± 7 pmol·s(-1)·mg(-1)) and ETS (107 ± 4 to 143 ± 14 pmol·s(-1)·mg(-1), p < 0.05), demonstrating that Epo treatment induces an upregulation of OXPHOS and ETS in human skeletal muscle.

Original language	English
Journal	Frontiers in Physiology
Volume	3
Pages (from-to)	50
ISSN	1664-042X
DOIs	https://doi.org/10.3389/fphys.2012.00050
Publication status	Published - 2012

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10.3389/fphys.2012.00050

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title = "Erythropoietin treatment enhances muscle mitochondrial capacity in humans",

abstract = "Erythropoietin (Epo) treatment has been shown to induce mitochondrial biogenesis in cardiac muscle along with enhanced mitochondrial capacity in mice. We hypothesized that recombinant human Epo (rhEpo) treatment enhances skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over 8 weeks with oral iron (100 mg) supplementation taken daily. Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis before and after rhEpo treatment. OXPHOS was determined with the mitochondrial complex I substrates malate, glutamate, pyruvate, and complex II substrate succinate in the presence of saturating ADP concentrations, while maximal electron transport capacity (ETS) was assessed by addition of an uncoupler. rhEpo treatment increased OXPHOS (from 92 ± 5 to 113 ± 7 pmol·s(-1)·mg(-1)) and ETS (107 ± 4 to 143 ± 14 pmol·s(-1)·mg(-1), p < 0.05), demonstrating that Epo treatment induces an upregulation of OXPHOS and ETS in human skeletal muscle.",

author = "Ulla Plenge and Bo Belhage and Amelia Guadalupe-Grau and Andersen, {Peter Riis} and Carsten Lundby and Flemming Dela and Nis Stride and Pott, {Frank Christian} and Helge, {J{\o}rn Wulff} and Robert Boushel",

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doi = "10.3389/fphys.2012.00050",

language = "English",

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journal = "Frontiers in Physiology",

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T1 - Erythropoietin treatment enhances muscle mitochondrial capacity in humans

AU - Plenge, Ulla

AU - Belhage, Bo

AU - Guadalupe-Grau, Amelia

AU - Andersen, Peter Riis

AU - Lundby, Carsten

AU - Dela, Flemming

AU - Stride, Nis

AU - Pott, Frank Christian

AU - Helge, Jørn Wulff

AU - Boushel, Robert

PY - 2012

Y1 - 2012

N2 - Erythropoietin (Epo) treatment has been shown to induce mitochondrial biogenesis in cardiac muscle along with enhanced mitochondrial capacity in mice. We hypothesized that recombinant human Epo (rhEpo) treatment enhances skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over 8 weeks with oral iron (100 mg) supplementation taken daily. Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis before and after rhEpo treatment. OXPHOS was determined with the mitochondrial complex I substrates malate, glutamate, pyruvate, and complex II substrate succinate in the presence of saturating ADP concentrations, while maximal electron transport capacity (ETS) was assessed by addition of an uncoupler. rhEpo treatment increased OXPHOS (from 92 ± 5 to 113 ± 7 pmol·s(-1)·mg(-1)) and ETS (107 ± 4 to 143 ± 14 pmol·s(-1)·mg(-1), p < 0.05), demonstrating that Epo treatment induces an upregulation of OXPHOS and ETS in human skeletal muscle.

AB - Erythropoietin (Epo) treatment has been shown to induce mitochondrial biogenesis in cardiac muscle along with enhanced mitochondrial capacity in mice. We hypothesized that recombinant human Epo (rhEpo) treatment enhances skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over 8 weeks with oral iron (100 mg) supplementation taken daily. Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis before and after rhEpo treatment. OXPHOS was determined with the mitochondrial complex I substrates malate, glutamate, pyruvate, and complex II substrate succinate in the presence of saturating ADP concentrations, while maximal electron transport capacity (ETS) was assessed by addition of an uncoupler. rhEpo treatment increased OXPHOS (from 92 ± 5 to 113 ± 7 pmol·s(-1)·mg(-1)) and ETS (107 ± 4 to 143 ± 14 pmol·s(-1)·mg(-1), p < 0.05), demonstrating that Epo treatment induces an upregulation of OXPHOS and ETS in human skeletal muscle.

U2 - 10.3389/fphys.2012.00050

DO - 10.3389/fphys.2012.00050

M3 - Journal article

C2 - 22419911

SN - 1664-042X

VL - 3

SP - 50

JO - Frontiers in Physiology

JF - Frontiers in Physiology

ER -

Erythropoietin treatment enhances muscle mitochondrial capacity in humans

Abstract

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