title: Expression of the irisin precursor FNDC5 in skeletal muscle correlates with aerobic exercise performance in patients with heart failure.
abstract: BACKGROUND
  Exercise-induced increase in peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) expression has been shown to increase the expression of the fibronectin type III domain containing 5 (FNDC5) gene and thereby its product, irisin, in mice. Given that exercise intolerance is a hallmark characteristic of heart failure (HF), and because PGC-1α and irisin promote exercise benefits in animals, we hypothesized that expression of these genes relates to aerobic performance in patients with HF.
  
  
  RESULTS
  Systolic HF (left ventricular ejection fraction ≤40%) patients underwent cardiopulmonary exercise testing to evaluate aerobic performance. High versus low aerobic performance was assessed using oxygen consumption (peak Vo(2) [>14 versus ≤14 mL O(2)·kg(-1)·min(-1)]) and ventilatory efficiency (VE/Vco(2) slope [<34 versus ≥34]). Muscle biopsies of the vastus lateralis and real-time polymerase chain reaction were used to quantify muscle gene expression. Twenty-four patients were studied. FNDC5 (5.7±3.5 versus 3.1±1.2, P<0.05) and PGC-1α (9.9±5.9 versus 4.5±1.9, P<0.01) gene expressions were greater in the high-peak Vo(2) group; correlation between FNDC5 and PGC-1α was significant (r=0.56, P<0.05) only in the high-peak Vo(2) group. Similarly, FNDC5 and PGC-1α gene expression was greater in the high-performance group based on lower VE/Vco(2) slopes (5.8±3.6 versus 3.3±1.4, P<0.05 and 9.7±6 versus 5.3±3.4, P<0.05); FNDC5 also correlated with PGC-1α (r=0.55, P<0.05) only in the low VE/Vco(2) slope group.
  
  
  CONCLUSIONS
  This is the first study to show that FNDC5 expression relates to functional capacity in a human HF population. Lower FNDC5 expression may underlie reduced aerobic performance in HF patients.
authors.affiliation: Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: Stewart H
authors.initials: SH
authors.lastname: Lecker
authors.forename: Alexandra
authors.initials: A
authors.lastname: Zavin
authors.forename: Peirang
authors.initials: P
authors.lastname: Cao
authors.forename: Ross
authors.initials: R
authors.lastname: Arena
authors.forename: Kelly
authors.initials: K
authors.lastname: Allsup
authors.forename: Karla M
authors.initials: KM
authors.lastname: Daniels
authors.forename: Jacob
authors.initials: J
authors.lastname: Joseph
authors.forename: P Christian
authors.initials: PC
authors.lastname: Schulze
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Forman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D015444:Exercise / Q000502:physiology*; D005353:Fibronectins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D010101:Oxygen Consumption / Q000502:physiology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012189:Retrospective Studies; D013318:Stroke Volume / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C577593:FNDC5 protein, human; D005353:Fibronectins; D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors