title: Effect of endurance training on skeletal muscle myokine expression in obese men: identification of apelin as a novel myokine.
abstract: BACKGROUND
  It has been suggested that the metabolic benefits of physical exercise could be mediated by myokines. We examined here the effect of exercise training on skeletal muscle expression of a panel of myokines in humans. Pathways regulating myokine expression were investigated in human myotubes.
  
  
  METHODS
  Eleven obese non-diabetic male subjects were enrolled in an 8-week endurance training program. Insulin sensitivity was assessed by an oral glucose tolerance test. Subcutaneous adipose tissue and Vastus lateralis muscle biopsy samples were collected before and after training. RNAs were prepared from adipose tissue and skeletal muscle. Primary culture of myoblasts was established.
  
  
  RESULTS
  As expected, exercise training improved aerobic capacity and decreased fat mass. No significant change in interleukin 6, fibroblast growth factor 21, myostatin (MSTN) or irisin mRNA level was found in muscle after training. A twofold increase in apelin mRNA level was found in muscle but not in adipose tissue. No change in circulating myokine and adipokine plasma levels was observed in the resting state in response to training. Interestingly, apelin was significantly expressed and secreted in primary human myotubes. Apelin gene expression was upregulated by cyclic AMP and calcium, unlike the other myokines investigated. Importantly, changes in muscle apelin mRNA levels were positively related to whole-body insulin sensitivity improvement.
  
  
  CONCLUSIONS
  Collectively, our data show that exercise training upregulates muscle apelin expression in obese subjects. Apelin expression is induced by exercise signaling pathways and secreted in vitro in human primary myotubes, and may behave as a novel exercise-regulated myokine with autocrine/paracrine action.
authors: 1] Inserm, UMR1048, Obesity Research Laboratory, I2MC, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France [2] University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
authors: A
authors: A
authors: Besse-Patin
authors: 1] Inserm, UMR1048, Obesity Research Laboratory, I2MC, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France [2] University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France [3] Nutrition and Clinical Biochemistry Departments, Toulouse University Hospitals, Toulouse, France.
authors: E
authors: E
authors: Montastier
authors: 1] University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France [2] Inserm, UMR1048, Adipolab, I2MC, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.
authors: C
authors: C
authors: Vinel
authors: 1] University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France [2] Inserm, UMR1048, Adipolab, I2MC, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.
authors: I
authors: I
authors: Castan-Laurell
authors: 1] Inserm, UMR1048, Obesity Research Laboratory, I2MC, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France [2] University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
authors: K
authors: K
authors: Louche
authors: 1] University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France [2] Inserm, UMR1048, Adipolab, I2MC, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.
authors: C
authors: C
authors: Dray
authors: 1] University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France [2] Inserm, UMR1048, Adipolab, I2MC, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.
authors: D
authors: D
authors: Daviaud
authors: 1] Inserm, UMR1048, Obesity Research Laboratory, I2MC, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France [2] University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
authors: L
authors: L
authors: Mir
authors: 1] Inserm, UMR1048, Obesity Research Laboratory, I2MC, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France [2] University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
authors: M-A
authors: MA
authors: Marques
authors: 1] Inserm, UMR1048, Obesity Research Laboratory, I2MC, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France [2] University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France [3] Clinical Investigation Centre Inserm, CIC-9302, Department of Clinical Pharmacology, Toulouse University Hospitals, Toulouse, France.
authors: C
authors: C
authors: Thalamas
authors: 1] University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France [2] Nutrition and Clinical Biochemistry Departments, Toulouse University Hospitals, Toulouse, France.
authors: P
authors: P
authors: Valet
authors: 1] Inserm, UMR1048, Obesity Research Laboratory, I2MC, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France [2] University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France [3] Nutrition and Clinical Biochemistry Departments, Toulouse University Hospitals, Toulouse, France.
authors: D
authors: D
authors: Langin
authors: 1] Inserm, UMR1048, Obesity Research Laboratory, I2MC, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France [2] University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
authors: C
authors: C
authors: Moro
authors: 1] Inserm, UMR1048, Obesity Research Laboratory, I2MC, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France [2] University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
authors: N
authors: N
authors: Viguerie
mesh_terms: D000328:Adult; D000073861:Apelin; D015444:Exercise; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D055435:Myostatin / Q000378:metabolism; D009765:Obesity / Q000378:metabolism* / Q000517:prevention & control; D010807:Physical Endurance; D050151:Subcutaneous Fat / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C115436:APLN protein, human; D000073861:Apelin; C577593:FNDC5 protein, human; D005353:Fibronectins; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; C525911:MSTN protein, human; D055435:Myostatin; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
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