title: Skeletal muscle atrophy in sedentary Zucker obese rats is not caused by calpain-mediated muscle damage or lipid peroxidation induced by oxidative stress.
abstract: BACKGROUND
  Skeletal muscle undergoes significant atrophy in Type 2 diabetic patients and animal models. We aimed to determine if atrophy of Zucker rat skeletal muscle was due to the activation of intracellular damage pathways induced by excess reactive oxygen species production (specifically those associated with the peroxidation of lipid membranes) and calpain activity. 14 week old obese Zucker rats and littermate lean controls were injected with 1% Evan's Blue Dye. Animals were anaesthetised and extensor digitorum longus and soleus muscles were dissected, snap frozen and analysed for ROS-mediated F2-isoprostane production and calpain activation/autolysis. Contralateral muscles were histologically analysed for markers of muscle membrane permeability and atrophy.
  
  
  RESULTS
  Muscle mass was lower in extensor digitorum longus and soleus of obese compared with lean animals, concomitant with reduced fibre area. Muscles from obese rats had a higher proportional area of Evan's Blue Dye fluorescence, albeit this was localised to the interstitium/external sarcolemma. There were no differences in F2-isoprostane production when expressed relative to arachidonic acid content, which was lower in the obese EDL and soleus muscles. There were no differences in the activation of either μ-calpain or calpain-3.
  
  
  CONCLUSIONS
  This study highlights that atrophy of Zucker rat skeletal muscle is not related to sarcolemmal damage, sustained hyperactivation of the calpain proteases or excessive lipid peroxidation. As such, establishing the correct pathways involved in atrophy is highly important so as to develop more specific treatment options that target the underlying cause. This study has eliminated two of the potential pathways theorised to be responsible.
authors.affiliation: Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, Melbourne, Australia. nancycapitanio@hotmail.com.
authors.forename: Nancy
authors.initials: N
authors.lastname: Pompeani
authors.affiliation: Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, Melbourne, Australia. emma.rybalka@vu.edu.au.|Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, Australia. emma.rybalka@vu.edu.au.
authors.forename: Emma
authors.initials: E
authors.lastname: Rybalka
authors.affiliation: Department of Zoology, La Trobe University, Melbourne, Australia. H.Latchman@latrobe.edu.au.
authors.forename: Heidy
authors.initials: H
authors.lastname: Latchman
authors.affiliation: Department of Zoology, La Trobe University, Melbourne, Australia. R.Murphy@latrobe.edu.au.
authors.forename: Robyn M
authors.initials: RM
authors.lastname: Murphy
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Australia. kevin.croft@uwa.edu.au.
authors.forename: Kevin
authors.initials: K
authors.lastname: Croft
authors.affiliation: Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, Melbourne, Australia. alan.hayes@vu.edu.au.|Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, Australia. alan.hayes@vu.edu.au.
authors.forename: Alan
authors.initials: A
authors.lastname: Hayes
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D002154:Calpain / Q000502:physiology*; D015227:Lipid Peroxidation / Q000502:physiology*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D011924:Rats, Zucker
chemical_list: D001786:Blood Glucose; D002154:Calpain