title: Exercise training and return to a well-balanced diet activate the neuregulin 1/ErbB pathway in skeletal muscle of obese rats.
abstract: CONCLUSIONS
  Some studies suggest that neuregulin 1 (NRG1) could be involved in the regulation of skeletal muscle energy metabolism in rodents. Here we assessed whether unbalanced diet is associated with alterations of the NRG1 signalling pathway and whether exercise and diet might restore NRG1 signalling in skeletal muscle of obese rats. We show that diet-induced obesity does not impair NRG1 signalling in rat skeletal muscle. We also report that endurance training and a well-balanced diet activate the NRG1 signalling in skeletal muscle of obese rats, possibly via a new mechanism mediated by the protease ADAM17. These results suggest that some beneficial effects of physical activity and diet in obese rats could be partly explained by stimulation of the NRG1 signalling pathway.
  Some studies suggest that the signalling pathway of neuregulin 1 (NRG1), a protein involved in the regulation of skeletal muscle metabolism, could be altered by nutritional and exercise interventions. We hypothesized that diet-induced obesity could lead to alterations of the NRG1 signalling pathway and that chronic exercise could improve NRG1 signalling in rat skeletal muscle. To test this hypothesis, male Wistar rats received a high fat/high sucrose (HF/HS) diet for 16 weeks. At the end of this period, NRG1 and ErbB expression/activity in skeletal muscle was assessed. The obese rats then continued the HF/HS diet or were switched to a well-balanced diet. Moreover, in both groups, half of the animals also performed low intensity treadmill exercise training. After another 8 weeks, NRG1 and ErbB expression/activity in skeletal muscle were tested again. The 16 week HF/HS diet induced obesity, but did not significantly affect the NRG1/ErbB signalling pathway in rat skeletal muscle. Conversely, after the switch to a well-balanced diet, NRG1 cleavage ratio and ErbB4 amount were increased. Chronic exercise training also promoted NRG1 cleavage, resulting in increased ErbB4 phosphorylation. This result was associated with increased protein expression and phosphorylation ratio of the metalloprotease ADAM17, which is involved in NRG1 shedding. Similarly, in vitro stretch-induced activation of ADAM17 in rat myoblasts induced NRG1 cleavage and ErbB4 activation. These results show that low intensity endurance training and well-balanced diet activate the NRG1-ErbB4 pathway, possibly via the metalloprotease ADAM17, in skeletal muscle of diet-induced obese rats.
authors.affiliation: Université Clermont Auvergne, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), BP 80026, F-63171, Aubière Cedex, France.|CRNH-Auvergne, Clermont-Ferrand, F-63001, France.
authors.forename: Gaël
authors.initials: G
authors.lastname: Ennequin
authors.affiliation: Université Clermont Auvergne, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), BP 80026, F-63171, Aubière Cedex, France.|CRNH-Auvergne, Clermont-Ferrand, F-63001, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Boisseau
authors.affiliation: Université Clermont Auvergne, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), BP 80026, F-63171, Aubière Cedex, France.|CRNH-Auvergne, Clermont-Ferrand, F-63001, France.
authors.forename: Kevin
authors.initials: K
authors.lastname: Caillaud
authors.affiliation: Université Clermont Auvergne, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), BP 80026, F-63171, Aubière Cedex, France.|CRNH-Auvergne, Clermont-Ferrand, F-63001, France.
authors.forename: Vivien
authors.initials: V
authors.lastname: Chavanelle
authors.affiliation: Université Clermont Auvergne, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), BP 80026, F-63171, Aubière Cedex, France.|CRNH-Auvergne, Clermont-Ferrand, F-63001, France.
authors.forename: Maude
authors.initials: M
authors.lastname: Gerbaix
authors.affiliation: Université Clermont Auvergne, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), BP 80026, F-63171, Aubière Cedex, France.|CRNH-Auvergne, Clermont-Ferrand, F-63001, France.
authors.forename: Lore
authors.initials: L
authors.lastname: Metz
authors.affiliation: Université Clermont Auvergne, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), BP 80026, F-63171, Aubière Cedex, France.|CRNH-Auvergne, Clermont-Ferrand, F-63001, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Etienne
authors.affiliation: CRNH-Auvergne, Clermont-Ferrand, F-63001, France.|INRA, UMR 1019, Clermont-Ferrand, F-63001, France.|University Clermont 1, UFR Médecine, Clermont-Ferrand, F-63001, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Walrand
authors.affiliation: CRNH-Auvergne, Clermont-Ferrand, F-63001, France.|INRA, UMR 1019, Clermont-Ferrand, F-63001, France.|University Clermont 1, UFR Médecine, Clermont-Ferrand, F-63001, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Masgrau
authors.affiliation: CRNH-Auvergne, Clermont-Ferrand, F-63001, France.|INRA, UMR 1019, Clermont-Ferrand, F-63001, France.|University Clermont 1, UFR Médecine, Clermont-Ferrand, F-63001, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Guillet
authors.affiliation: Université Clermont Auvergne, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), BP 80026, F-63171, Aubière Cedex, France.|CRNH-Auvergne, Clermont-Ferrand, F-63001, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Courteix
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas Health Science Centre, Houston, TX, 77030, USA.
authors.forename: Airu
authors.initials: A
authors.lastname: Niu
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas Health Science Centre, Houston, TX, 77030, USA.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Li
authors.affiliation: CRNH-Auvergne, Clermont-Ferrand, F-63001, France.|INRA, UMR 1019, Clermont-Ferrand, F-63001, France.|University Clermont 1, UFR Médecine, Clermont-Ferrand, F-63001, France.
authors.forename: Fréderic
authors.initials: F
authors.lastname: Capel
authors.affiliation: Université Clermont Auvergne, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), BP 80026, F-63171, Aubière Cedex, France.|CRNH-Auvergne, Clermont-Ferrand, F-63001, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Sirvent
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D000818:Animals; D004032:Diet; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D032446:Myoblasts / Q000378:metabolism; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D015398:Signal Transduction; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism
chemical_list: D020890:Neuregulin-1; C490580:Nrg1 protein, rat; D012333:RNA, Messenger; D019717:Tissue Inhibitor of Metalloproteinase-3; D066246:ErbB Receptors; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606464:Adam17 protein, rat
references.citation: Diabetes. 2007 Sep;56(9):2185-93
references.pmid: 17563068
references.citation: J Physiol. 2012 Oct 15;590(20):5199-210
references.pmid: 22802586
references.citation: Bone. 2013 Apr;53(2):382-90
references.pmid: 23318975
references.citation: Diabetes. 2009 Oct;58(10):2396-401
references.pmid: 19581416
references.citation: J Appl Physiol Respir Environ Exerc Physiol. 1979 Dec;47(6):1278-83
references.pmid: 536299
references.citation: J Biol Chem. 2006 Aug 4;281(31):21690-7
references.pmid: 16740635
references.citation: J Sports Sci Med. 2014 Sep 01;13(3):689-94
references.pmid: 25177200
references.citation: J Biol Chem. 2001 May 25;276(21):18257-64
references.pmid: 11278386
references.citation: J Cell Sci. 2013 Oct 1;126(Pt 19):4349-57
references.pmid: 23868980
references.citation: Eur J Appl Physiol. 2005 Jul;94(4):371-5
references.pmid: 15875210
references.citation: Folia Biol (Praha). 2009;55(3):85-91
references.pmid: 19545487
references.citation: Open Biomark J. 2009;2:1-5
references.pmid: 20634924
references.citation: Mol Cell Neurosci. 2000 Nov;16(5):631-48
references.pmid: 11083924
references.citation: J Biol Chem. 1994 May 13;269(19):14303-6
references.pmid: 8188716
references.citation: Nutr Metab Cardiovasc Dis. 2010 Dec;20(10):698-705
references.pmid: 19819120
references.citation: Methods Mol Biol. 2015;1295:381-91
references.pmid: 25820735
references.citation: Am J Physiol Endocrinol Metab. 2010 Apr;298(4):E742-50
references.pmid: 20028964
references.citation: Lipids Health Dis. 2012;11:91
references.pmid: 22781503
references.citation: Biochem Biophys Res Commun. 2009 Jan 30;379(1):32-7
references.pmid: 19070592
references.citation: J Biol Chem. 2001 Jan 26;276(4):2841-51
references.pmid: 11042203
references.citation: Dev Biol. 2005 Jul 15;283(2):459-71
references.pmid: 15936750
references.citation: Diabetes Metab. 2015 Apr;41(2):168-72
references.pmid: 25573691
references.citation: J Biol Chem. 2001 Nov 23;276(47):44099-107
references.pmid: 11495899
references.citation: Nature. 1993 Dec 2;366(6454):473-5
references.pmid: 7902537
references.citation: Novartis Found Symp. 2008;289:74-84; discussion 84-93
references.pmid: 18497096
references.citation: J Biol Chem. 2004 Mar 26;279(13):12260-8
references.pmid: 14711829
references.citation: J Cell Sci. 2007 Feb 15;120(Pt 4):692-701
references.pmid: 17264149
references.citation: Am J Physiol Cell Physiol. 2003 May;284(5):C1149-55
references.pmid: 12519750
references.citation: J Biol Chem. 2001 Mar 23;276(12):9352-8
references.pmid: 11116142
references.citation: Am J Pathol. 2005 Jun;166(6):1733-40
references.pmid: 15920158
references.citation: Hypertension. 2010 Oct;56(4):629-35
references.pmid: 20644006
references.citation: Lipids Health Dis. 2010;9:60
references.pmid: 20534152
references.citation: Nutr Clin Pract. 2011 Oct;26(5):512-25
references.pmid: 21947634
references.citation: J Exerc Nutrition Biochem. 2013 Dec;17(4):199-207
references.pmid: 25566431
references.citation: Development. 1997 Sep;124(18):3575-86
references.pmid: 9342050
references.citation: Exp Gerontol. 2006 May;41(5):525-31
references.pmid: 16564664