title: Elevated skeletal muscle irisin precursor FNDC5 mRNA in obese OLETF rats.
abstract: OBJECTIVE
  There is debate as to whether fibronectin type III domain containing 5 (FNDC5) and its protein product irisin are therapeutic targets for obesity-associated maladies. Thus, we sought to examine FNDC5 mRNA within skeletal muscle of obese/diabetic-prone Otsuka Long-Evans Tokushima Fatty (OLETF) rats versus lean/healthy Long Evans Tokushima Otsuka (LETO) rats. We hypothesized that FNDC5 expression would be greater in obese (OLETF) versus lean (LETO) animals.
  
  
  METHODS
  Triceps muscle of 30-32week old OLETF and LETO rats were assayed for FNDC5 and PGC1α mRNA levels. Body composition and circulating biomarkers of the OLETF and LETO rats were also correlated with skeletal muscle FNDC5 mRNA expression patterns in order to examine potential relationships that may exist.
  
  
  RESULTS
  OLETF rats exhibited twice the amount of triceps FNDC5 mRNA compared to LETO rats (p<0.01). Significant positive correlations existed between triceps muscle FNDC5 mRNA expression patterns versus fat mass (r=0.70, p=0.008), as well as plasma leptin (r=0.82, p<0.001). PGC1α mRNA levels were also highly correlated with FNDC5 mRNA (r=0.85, p<0.001). In subsequent culture experiments, low and high physiological doses of leptin had no effect on PGC1α mRNA or FNDC5 mRNA levels in C2C12 myotubes. Paradoxically, circulating irisin concentrations tended to be higher in a second cohort of LETO versus OLETF rats (p=0.085).
  
  
  CONCLUSIONS
  These results reveal a positive association between total body adiposity and skeletal muscle FNDC5 gene expression. Of interest, circulating irisin levels tended to be lower in OLETF rats. Further research is needed to examine whether other adipose tissue-derived factors up-regulate FNDC5 transcription and/or inhibit irisin biosynthesis from FNDC5.
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Roberts
authors.forename: David S
authors.initials: DS
authors.lastname: Bayless
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Company
authors.forename: Nathan T
authors.initials: NT
authors.lastname: Jenkins
authors.forename: Jaume
authors.initials: J
authors.lastname: Padilla
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Childs
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Martin
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Dalbo
authors.forename: Frank W
authors.initials: FW
authors.lastname: Booth
authors.forename: R Scott
authors.initials: RS
authors.lastname: Rector
authors.forename: M Harold
authors.initials: MH
authors.lastname: Laughlin
mesh_terms: D015502:Absorptiometry, Photon; D054392:Adipokines / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers; D001823:Body Composition / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D005353:Fibronectins / Q000096:biosynthesis* / Q000235:genetics*; D020738:Leptin / Q000097:blood; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism; D009765:Obesity / Q000235:genetics* / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D020334:Rats, Inbred OLETF; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
chemical_list: D054392:Adipokines; D015415:Biomarkers; D016207:Cytokines; C583676:FNDC5 protein, rat; D005353:Fibronectins; D020738:Leptin; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors
keywords: FNDC5; Irisin; LETO; Long Evans Tokushima Otsuka; OLETF; Obesity; Otsuka Long-Evans Tokushima Fatty; PGC1α; Peroxisome proliferator-activated receptor gamma coactivator 1-alpha; Skeletal muscle; fibronectin type III domain containing 5