title: The roles of aerobic exercise training and suppression IL-6 gene expression by RNA interference in the development of insulin resistance.
abstract: OBJECTIVE
  To demonstrate the hypothesis that aerobic exercise training inhibits the development of insulin resistance through IL-6 and probe into the possible molecular mechanism about it.
  
  
  METHODS
  Rats were raised with high-fat diets for 8 weeks to develop insulin resistance, and glucose infusion rates (GIRs) were determined by hyperinsulinemic-euglycemic clamping to confirm the development of insulin resistance. Aerobic exercise training (the speed and duration time in the first week were respectively 16 m/min and 50 min, and speed increased 1m/min and duration time increased 5 min every week following it) and/or IL-6shRNA plasmid injection (rats received IL-6shRNA injection via the tail vein every two weeks) were adopted during the development of insulin resistance. The serum IL-6, leptin, adiponectin, fasting blood glucose, fasting serum insulin, GIR, IL-6 gene expression levels, p-p38 in various tissues and p-STAT3/t-STAT3 ratio in the liver were measured.
  
  
  RESULTS
  Rats fed with high-fat diets for 8 weeks were developed insulin resistance and the IL-6mRNA levels of IL-6shRNA injection groups in various tissues were significantly lower than those of control group (P<0.05), respectively. The development of insulin resistance in exercise rats significantly decreased, however, compared with that, the GIR of exercise rats injected by IL-6shRNA was lower (P<0.05). The IL-6mRNA levels were highest in the fat tissue and lowest in the skeletal muscles in all the rats. The serum adiponectin levels decreased (P<0.05) following the development of insulin resistance, and it increased (P<0.05) when the rats were intervened by aerobic exercise training for 8 weeks at the same time. However, there were not significant differences when serum leptin concentrations were compared (P>0.05). The p-p38 significantly increased in the rats fed with high-fat diets, however, p-p38 of the exercise high-fat diets rats in the liver and fat tissues significantly decreased than that (P<0.05). The changes of p-p38 in exercise rats injected by IL-6shRNA were irregular. The activation of STAT3 in the liver significantly increased (P<0.05) following the development of insulin resistance, and it decreased (P<0.05) when the rats were intervened by aerobic exercise training for 8 weeks at the same time, and the gene silencing of IL-6 did not have effects on the activation of STAT3 in the liver (P>0.05).
  
  
  CONCLUSIONS
  In conclusion, aerobic exercise training prevented the development of insulin resistance through IL-6 to a certain degree. The gene expression and secretion of IL-6 could inhibit the development of insulin resistance. The mechanism of the effects were possibly related with elevating the levels of serum adiponectin, and/or inhibiting the activation of STAT3 in the liver and p38MAPK in the skeletal muscles, liver and fat tissues.
authors.affiliation: Department of Physical Education, Hunan University of Science and Technology, Xiangtan, Hunan Province, China. tanghui19730711@163.com
authors.forename: Hui
authors.initials: H
authors.lastname: Tang
authors.forename: Min-hao
authors.initials: MH
authors.lastname: Xie
authors.forename: Yu
authors.initials: Y
authors.lastname: Lei
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.forename: Yu-ping
authors.initials: YP
authors.lastname: Xu
authors.forename: Jian-guang
authors.initials: JG
authors.lastname: Cai
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D059305:Diet, High-Fat; D005786:Gene Expression Regulation; D007333:Insulin Resistance / Q000235:genetics*; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D020738:Leptin / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D010805:Physical Conditioning, Animal; D010957:Plasmids / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D052242:Adiponectin; D015850:Interleukin-6; D020738:Leptin; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D048051:p38 Mitogen-Activated Protein Kinases