title: Skeletal muscle myotubes in severe obesity exhibit altered ubiquitin-proteasome and autophagic/lysosomal proteolytic flux.
abstract: OBJECTIVE
  Whole-body protein metabolism is dysregulated with obesity. The goal of the study was to determine whether activity and expression of major protein degradation pathways are compromised specifically in human skeletal muscle with obesity.
  
  
  METHODS
  Primary human skeletal muscle (HSkM) cell cultures were utilized since cellular mechanisms can be studied absent of hormones and contractile activity that could independently influence metabolism. HSkM from 10 lean women (BMI ≤ 26.0 kg/m(2) ) and 8 women with severe obesity (BMI ≥ 39.0) were examined basally and when stimulated to atrophy (serum and amino acid starvation).
  
  
  RESULTS
  HSkM from obese donors had a lower proportion of type I myosin heavy chain and slower flux through the autophagic/lysosomal pathway. During starvation, flux through the ubiquitin-proteasome system diverged according to obesity status, with a decrease in lean subjects and an increase in HSkM from subjects with obesity. HSkM in obesity also displayed elevated proteasome activity despite no difference in proteasome content. Atrophy-related gene expression and myotube area were similar in myotubes derived from individuals with and without obesity under basal and starved conditions.
  
  
  CONCLUSIONS
  Our data indicate that muscle cells in lean individuals and in those with severe obesity have innate differences in management of protein degradation, which may explain their metabolic differences.
authors.affiliation: Department of Kinesiology, Human Performance Lab, College of Health and Human Performance, East Carolina University, Greenville, North Carolina, USA.|Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA.|Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA.|East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina, USA.
authors.forename: Lance M
authors.initials: LM
authors.lastname: Bollinger
authors.affiliation: Department of Kinesiology, Human Performance Lab, College of Health and Human Performance, East Carolina University, Greenville, North Carolina, USA.
authors.forename: Jonathan J S
authors.initials: JJ
authors.lastname: Powell
authors.affiliation: Department of Kinesiology, Human Performance Lab, College of Health and Human Performance, East Carolina University, Greenville, North Carolina, USA.|East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Houmard
authors.affiliation: Department of Kinesiology, Human Performance Lab, College of Health and Human Performance, East Carolina University, Greenville, North Carolina, USA.|Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA.|Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA.|East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina, USA.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Witczak
authors.affiliation: Department of Kinesiology, Human Performance Lab, College of Health and Human Performance, East Carolina University, Greenville, North Carolina, USA.|Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA.|Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA.|East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Brault
mesh_terms: D000328:Adult; D001343:Autophagy; D018929:Cell Culture Techniques; D005260:Female; D015870:Gene Expression; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009767:Obesity, Morbid / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D025801:Ubiquitin / Q000378:metabolism*; D055815:Young Adult
chemical_list: D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex