title: Natriuretic peptides enhance the oxidative capacity of human skeletal muscle.
abstract: Cardiac natriuretic peptides (NP) are major activators of human fat cell lipolysis and have recently been shown to control brown fat thermogenesis. Here, we investigated the physiological role of NP on the oxidative metabolism of human skeletal muscle. NP receptor type A (NPRA) gene expression was positively correlated to mRNA levels of PPARγ coactivator-1α (PGC1A) and several oxidative phosphorylation (OXPHOS) genes in human skeletal muscle. Further, the expression of NPRA, PGC1A, and OXPHOS genes was coordinately upregulated in response to aerobic exercise training in human skeletal muscle. In human myotubes, NP induced PGC-1α and mitochondrial OXPHOS gene expression in a cyclic GMP-dependent manner. NP treatment increased OXPHOS protein expression, fat oxidation, and maximal respiration independent of substantial changes in mitochondrial proliferation and mass. Treatment of myotubes with NP recapitulated the effect of exercise training on muscle fat oxidative capacity in vivo. Collectively, these data show that activation of NP signaling in human skeletal muscle enhances mitochondrial oxidative metabolism and fat oxidation. We propose that NP could contribute to exercise training-induced improvement in skeletal muscle fat oxidative capacity in humans.
authors.affiliation: Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Engeli
authors.forename: Andreas L
authors.initials: AL
authors.lastname: Birkenfeld
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Badin
authors.forename: Virginie
authors.initials: V
authors.lastname: Bourlier
authors.forename: Katie
authors.initials: K
authors.lastname: Louche
authors.forename: Nathalie
authors.initials: N
authors.lastname: Viguerie
authors.forename: Claire
authors.initials: C
authors.lastname: Thalamas
authors.forename: Emilie
authors.initials: E
authors.lastname: Montastier
authors.forename: Dominique
authors.initials: D
authors.lastname: Larrouy
authors.forename: Isabelle
authors.initials: I
authors.lastname: Harant
authors.forename: Isabelle
authors.initials: I
authors.lastname: de Glisezinski
authors.forename: Stefanie
authors.initials: S
authors.lastname: Lieske
authors.forename: Julia
authors.initials: J
authors.lastname: Reinke
authors.forename: Bibiana
authors.initials: B
authors.lastname: Beckmann
authors.forename: Dominique
authors.initials: D
authors.lastname: Langin
authors.forename: Jens
authors.initials: J
authors.lastname: Jordan
authors.forename: Cedric
authors.initials: C
authors.lastname: Moro
mesh_terms: D000222:Adaptation, Physiological; D000328:Adult; D009320:Atrial Natriuretic Factor / Q000502:physiology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D050259:Genes, Mitochondrial; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000502:physiology*; D009765:Obesity; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D061251:Primary Cell Culture; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A