title: An ethanolic extract of Artemisia dracunculus L. regulates gene expression of ubiquitin-proteasome system enzymes in skeletal muscle: potential role in the treatment of sarcopenic obesity.
abstract: OBJECTIVE
  Obesity is linked to insulin resistance, a primary component of metabolic syndrome and type 2 diabetes. The problem of obesity-related insulin resistance is compounded when age-related skeletal muscle loss, called sarcopenia, occurs with obesity. Skeletal muscle loss results from elevated levels of protein degradation and prevention of obesity-related sarcopenic muscle loss will depend on strategies that target pathways involved in protein degradation. An extract from Artemisia dracunculus, termed PMI 5011, improves insulin signaling and increases skeletal muscle myofiber size in a rodent model of obesity-related insulin resistance. The aim of this study was to examine the effect of PMI 5011 on the ubiquitin-proteasome system, a central regulator of muscle protein degradation.
  
  
  METHODS
  Gastrocnemius and vastus lateralis skeletal muscle was obtained from KK-A(y) obese diabetic mice fed a control or 1% (w/w) PMI 5011-supplemented diet. Regulation of genes encoding enzymes of the ubiquitin-proteasome system was determined using real-time quantitative reverse transcriptase polymerase chain reaction.
  
  
  RESULTS
  Although MuRF-1 ubiquitin ligase gene expression is consistently down-regulated in skeletal muscle, atrogin-1, Fbxo40, and Traf6 expression is differentially regulated by PMI 5011. Genes encoding other enzymes of the ubiquitin-proteasome system ranging from ubiquitin to ubiquitin-specific proteases are also regulated by PMI 5011. Additionally, expression of the gene encoding the microtubule-associated protein-1 light chain 3 (LC3), a ubiquitin-like protein pivotal to autophagy-mediated protein degradation, is down-regulated by PMI 5011 in the vastus lateralis.
  
  
  CONCLUSIONS
  PMI 5011 alters the gene expression of ubiquitin-proteasome system enzymes that are essential regulators of skeletal muscle mass. This suggests that PMI 5011 has therapeutic potential in the treatment of obesity-linked sarcopenia by regulating ubiquitin-proteasome-mediated protein degradation.
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Kirk-Ballard
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
authors.forename: Gail
authors.initials: G
authors.lastname: Kilroy
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
authors.forename: Britton C
authors.initials: BC
authors.lastname: Day
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
authors.forename: Zhong Q
authors.initials: ZQ
authors.lastname: Wang
authors.affiliation: Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Ribnicky
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Cefalu
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA. Electronic address: Elizabeth.Floyd@pbrc.edu.
authors.forename: Z Elizabeth
authors.initials: ZE
authors.lastname: Floyd
mesh_terms: D000818:Animals; D019306:Artemisia; D003920:Diabetes Mellitus / Q000378:metabolism; D044783:F-Box Proteins / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D008820:Mice, Obese; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D055948:Sarcopenia / Q000188:drug therapy / Q000378:metabolism*; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: D044783:F-Box Proteins; C525753:FBXO40 protein, mouse; D007328:Insulin; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D009124:Muscle Proteins; C541449:PMI-5011; D010936:Plant Extracts; D048029:TNF Receptor-Associated Factor 6; D000070584:Tripartite Motif Proteins; D014452:Ubiquitins; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex
keywords: Atrophy; Botanical; Proteasome; Ubiquitin