title: Decrease in myostatin by ladder-climbing training is associated with insulin resistance in diet-induced obese rats.
abstract: BACKGROUND
  Suppression of myostatin (MSTN) has been associated with skeletal muscle atrophy and insulin resistance (IR). However, few studies link MSTN suppression by ladder-climbing training (LCT) and IR. Therefore, we intended to identify the correlation with IR between LCT and to analyze the signaling pathways through which MSTN suppression by LCT regulates IR.
  
  
  METHODS
  The rats were randomly assigned to two types of diet: normal pellet diet (NPD, n = 8) and high-fat diet (HFD, n = 16). After 8 weeks, the HFD rats were randomly re-assigned to two groups (n = 8 for each group): HFD sedentary (HFD-S) and high-fat diet ladder-climbing training (HFD-LCT). HFD-LCT rats were assigned to LCT for 8 weeks. Western blotting, immunohistochemistry and enzyme assays were used to measure expression levels and activities of MSTN, GLUT4, PI3K, Akt and Akt-activated targets (mTOR, FoxO1 and GSK-3β).
  
  
  RESULTS
  The LCT significantly improved IR and whole-body insulin sensitivity in HDF-fed rats. MSTN protein levels decreased in matching serum (42%, P = 0.007) and muscle samples (25%, P = 0.035) and its receptor mRNA expression also decreased (16%, P = 0.041) from obese rats after LCT. But the mRNA expression of insulin receptor had no obvious changes in LCT group compared with NPD and HFD-S groups (P = 0.074). The ladder-climbing training significantly enhanced PI3K activity (1.7-fold, P = 0.024) and Akt phosphorylation (83.3%, P = 0.022) in HFD-fed rats, significantly increased GLUT4 protein expression (84.5%, P = 0.036), enhanced phosphorylation of mTOR (4.8-fold, P < 0.001) and inhibited phosphorylation of FoxO1 (57.7%, P = 0.020), but did not affect the phosphorylation of GSK-3β.
  
  
  CONCLUSIONS
  The LCT significantly reduced IR in diet-induced obese rats. MSTN may play an important role in regulating IR and fat accumulation by LCT via PI3K/Akt/mTOR and PI3K/Akt/FoxO1 signaling pathway in HFD-fed rats.
authors.affiliation: Institute of Sports Biology, Shaanxi Normal University, Xi'an, Shaanxi 710062, China. Email: tl531@snnu.edu.cn.
authors.forename: Liang
authors.initials: L
authors.lastname: Tang
authors.affiliation: Institute of Sports Biology, Shaanxi Normal University, Xi'an, Shaanxi 710062, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Luo
authors.affiliation: Department of Physical Education, Northwest University, Xi'an, Shaanxi 710069, China.
authors.forename: Chentao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Institute of Sports Biology, Shaanxi Normal University, Xi'an, Shaanxi 710062, China.
authors.forename: Xudan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Sports Biology, Shaanxi Normal University, Xi'an, Shaanxi 710062, China.
authors.forename: Didi
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Institute of Sports Biology, Shaanxi Normal University, Xi'an, Shaanxi 710062, China.
authors.forename: Aiping
authors.initials: A
authors.lastname: Chi
authors.affiliation: Institute of Sports Biology, Shaanxi Normal University, Xi'an, Shaanxi 710062, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Sports Biology, Shaanxi Normal University, Xi'an, Shaanxi 710062, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Sun
mesh_terms: D000818:Animals; D015153:Blotting, Western; D059305:Diet, High-Fat / Q000009:adverse effects; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007150:Immunohistochemistry; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D055435:Myostatin / Q000378:metabolism*; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D052097:Quadriceps Muscle / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051275:Glucose Transporter Type 4; D055435:Myostatin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt