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Expression of the Irisin Precursor FNDC5 in Skeletal Muscle Correlates with Aerobic Exercise Performance in Patients with Heart Failure.
MedLine Citation:
PMID:  23001918     Owner:  NLM     Status:  Publisher    
BACKGROUND: -Exercise induced increase in peroxisome proliferator-activated receptor-γ co-activator-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 since PGC-1α and irisin promote exercise benefits in animals, we hypothesized that expression of these genes relates to aerobic performance in patients with HF. METHODS AND RESULTS: -Systolic HF (LVEF ≤40%) patients underwent cardiopulmonary exercise testing (CPX) to evaluate aerobic performance. High vs. low aerobic performance was assessed using oxygen consumption [peak VO(2) (>14mlO(2)kg(-1)min(-1) vs. ≤14 mlO(2)kg(-1)min(-1))] and ventilatory efficiency [VE/VCO(2) slope (<34 vs. ≥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 vs. 3.1±1.2, p<.05) and PGC-1α (9.9±5.9 vs. 4.5±1.9, p<.01) gene expression was greater in the high peak VO(2) group; correlation between FNDC5 and PGC-1α was significant (r=0.56, p<.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 vs. 3.3±1.4, p<.05 and 9.7±6 vs. 5.3±3.4, p<.05); FNDC5 also correlated with PGC-1α (r=0.55, p<.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.
Stewart H Lecker; Alexandra Zavin; Peirang Cao; Ross Arena; Kelly Allsup; Karla M Daniels; Jacob Joseph; P Christian Schulze; Daniel E Forman
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-20
Journal Detail:
Title:  Circulation. Heart failure     Volume:  -     ISSN:  1941-3297     ISO Abbreviation:  Circ Heart Fail     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101479941     Medline TA:  Circ Heart Fail     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
1 Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA;
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