title: Myostatin decreases with aerobic exercise and associates with insulin resistance.
abstract: OBJECTIVE
  There is mounting evidence that skeletal muscle produces and secretes biologically active proteins or "myokines" that facilitate metabolic cross talk between organ systems. The increased expression of myostatin, a secreted anabolic inhibitor of muscle growth and development, has been associated with obesity and insulin resistance. Despite these intriguing findings, there have been few studies linking myostatin and insulin resistance.
  
  
  METHODS
  To explore this relationship in more detail, we quantified myostatin protein in muscle and plasma from 10 insulin-resistant, middle-aged (53.1 ± 5.5 yr) men before and after 6 months of moderate aerobic exercise training (1200 kcal·wk−¹ at 40%-55% VO2peak). To establish a cause-effect relationship, we also injected C57/Bl6 male mice with high physiological levels of recombinant myostatin protein.
  
  
  RESULTS
  Myostatin protein levels were shown to decrease in muscle (37%, P = 0.042, n = 10) and matching plasma samples (from 28.7 ng·mL−¹ pretraining to 22.8 ng·mL−¹ posttraining, P = 0.003, n = 9) with aerobic exercise. Furthermore, the strong correlation between plasma myostatin levels and insulin sensitivity (R² = 0.82, P < 0.001, n = 9) suggested a cause-effect relationship that was subsequently confirmed by inducing insulin resistance in myostatin-injected mice. A modest increase (44%) in plasma myostatin levels was also associated with significant reductions in the insulin-stimulated phosphorylation of Akt (Thr308) in both muscle and liver of myostatin-treated animals.
  
  
  CONCLUSIONS
  These findings indicate that both muscle and plasma myostatin protein levels are regulated by aerobic exercise and, furthermore, that myostatin is in the causal pathway of acquired insulin resistance with physical inactivity.
authors.affiliation: Human Performance Laboratory, Faculty of Kinesiology, Roger Jackson Center for Health and Wellness, University of Calgary, Calgary, Alberta, Canada. dhittel@kin.ucalgary.ca
authors.forename: Dustin S
authors.initials: DS
authors.lastname: Hittel
authors.forename: Michelle
authors.initials: M
authors.lastname: Axelson
authors.forename: Neha
authors.initials: N
authors.lastname: Sarna
authors.forename: Jane
authors.initials: J
authors.lastname: Shearer
authors.forename: Kim M
authors.initials: KM
authors.lastname: Huffman
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
mesh_terms: D000328:Adult; D000818:Animals; D001706:Biopsy; D004797:Enzyme-Linked Immunosorbent Assay; D015444:Exercise / Q000502:physiology*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D055435:Myostatin / Q000097:blood*; D010766:Phosphorylation / Q000502:physiology
chemical_list: C525911:MSTN protein, human; C525912:Mstn protein, mouse; D055435:Myostatin
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