title: Activation of the mitogen-activated protein kinase (MAPK) signalling pathway in the liver of mice is related to plasma glucose levels after acute exercise.
abstract: OBJECTIVE
  We aimed to identify, in the liver of mice, signal transduction pathways that show a pronounced regulation by acute exercise. We also aimed to elucidate the role of metabolic stress in this response.
  
  
  METHODS
  C57Bl6 mice performed a 60 min run on a treadmill under non-exhaustive conditions. Hepatic RNA and protein lysates were prepared immediately after running and used for whole-genome-expression analysis, quantitative real-time PCR and immunoblotting. A subset of mice recovered for 3 h after the treadmill run. A further group of mice performed the treadmill run after having received a vitamin C- and vitamin E-enriched diet over 4 weeks.
  
  
  RESULTS
  The highest number of genes differentially regulated by exercise in the liver was found in the mitogen-activated protein kinase (MAPK) signalling pathway, with a pronounced and transient upregulation of the transcription factors encoded by c-Fos (also known as Fos), c-Jun (also known as Jun), FosB (also known as Fosb) and JunB (also known as Junb) and phosphorylation of hepatic MAPK. Acute exercise also activated the p53 signalling pathway. A major role for oxidative stress is unlikely since the antioxidant-enriched diet did not prevent the activation of the MAPK pathway. In contrast, lower plasma glucose levels after running were related to enhanced levels of MAPK signalling proteins, similar to the upregulation of Igfbp1 and Pgc-1alpha (also known as Ppargc1a). In the working muscle the activation of the MAPK pathway was weak and not related to plasma glucose concentrations.
  
  
  CONCLUSIONS
  Metabolic stress evidenced as low plasma glucose levels appears to be an important determinant for the activation of the MAPK signalling pathway and the transcriptional response of the liver to acute exercise.
authors.affiliation: Division of Endocrinology, Diabetology, Angiology, Nephrology, Pathobiochemistry and Clinical Chemistry, Department of Internal Medicine, University Hospital of Tuebingen, Otfried-Mueller-Strasse 10, D-72076 Tuebingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hoene
authors.forename: H
authors.initials: H
authors.lastname: Franken
authors.forename: L
authors.initials: L
authors.lastname: Fritsche
authors.forename: R
authors.initials: R
authors.lastname: Lehmann
authors.forename: A K
authors.initials: AK
authors.lastname: Pohl
authors.forename: H U
authors.initials: HU
authors.lastname: Häring
authors.forename: A
authors.initials: A
authors.lastname: Zell
authors.forename: E D
authors.initials: ED
authors.lastname: Schleicher
authors.forename: C
authors.initials: C
authors.lastname: Weigert
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D015153:Blotting, Western; D055106:Genome-Wide Association Study; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016159:Tumor Suppressor Protein p53; D020928:Mitogen-Activated Protein Kinases