title: Exercise in ZDF rats does not attenuate weight gain, but prevents hyperglycemia concurrent with modulation of amino acid metabolism and AKT/mTOR activation in skeletal muscle.
abstract: OBJECTIVE
  Protein metabolism is altered in obesity, accompanied by elevated plasma amino acids (AA). Previously, we showed that exercise delayed progression to type 2 diabetes in obese ZDF rats with maintenance of β cell function and reduction in hyperglucocorticoidemia. We hypothesized that exercise would correct the abnormalities we found in circulating AA and other indices of skeletal muscle protein metabolism.
  
  
  METHODS
  Male obese prediabetic ZDF rats (7-10/group) were exercised (swimming) 1 h/day, 5 days/week from ages 6-19 weeks, and compared with age-matched obese sedentary and lean ZDF rats.
  
  
  RESULTS
  Food intake and weight gain were unaffected. Protein metabolism was altered in obese rats as evidenced by increased plasma concentrations of essential AA, and increased muscle phosphorylation (ph) of Akt(ser473) (187%), mTOR(ser2448) (140%), eIF4E-binding protein 1 (4E-BP1) (111%), and decreased formation of 4E-BP1*eIF4E complex (75%, 0.01 ≤ p ≤ 0.05 for all measures) in obese relative to lean rats. Exercise attenuated the increase in plasma essential AA concentrations and muscle Akt and mTOR phosphorylation. Exercise did not modify phosphorylation of S6K1, S6, and 4E-BP1, nor the formation of 4E-BP1*eIF4E complex, mRNA levels of ubiquitin or the ubiquitin ligase MAFbx. Positive correlations were observed between ph-Akt and fed circulating branched-chain AA (r = 0.56, p = 0.008), postprandial glucose (r = 0.42, p = 0.04) and glucose AUC during an IPGTT (r = 0.44, p = 0.03).
  
  
  CONCLUSIONS
  Swimming exercise-induced attenuation of hyperglycemia in ZDF rats is independent of changes in body weight and could result in part from modulation of muscle AKT activation acting via alterations of systemic AA metabolism.
authors.affiliation: Crabtree Nutrition Laboratories, Division of Endocrinology and Metabolism, Department of Medicine, McGill University Health Centre, Montreal, Canada, oadegoke@yorku.ca.
authors.forename: Olasunkanmi A J
authors.initials: OA
authors.lastname: Adegoke
authors.forename: Holly E
authors.initials: HE
authors.lastname: Bates
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kiraly
authors.forename: Mladen
authors.initials: M
authors.lastname: Vranic
authors.forename: Michael C
authors.initials: MC
authors.lastname: Riddell
authors.forename: Errol B
authors.initials: EB
authors.lastname: Marliss
mesh_terms: D000596:Amino Acids / Q000097:blood* / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000097:blood / Q000235:genetics; D006943:Hyperglycemia / Q000517:prevention & control*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism / Q000628:therapy; D010750:Phosphoproteins / Q000097:blood / Q000235:genetics; D010766:Phosphorylation; D010805:Physical Conditioning, Animal; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D015430:Weight Gain
chemical_list: D000596:Amino Acids; D002352:Carrier Proteins; C499526:Eif4ebp1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C546845:mTOR protein, rat; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; C526901:Rps6kb1 protein, rat; D058570:TOR Serine-Threonine Kinases