Expression of the Irisin Precursor FNDC5 in Skeletal Muscle Correlates with Aerobic Exercise Performance in Patients with Heart Failure
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 VO2 (>14mlO2●kg-1●min-1 vs. ≤14 mlO2●kg-1●min-1)] and ventilatory efficiency [VE/VCO2 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 VO2 group; correlation between FNDC5 and PGC-1α was significant (r=0.56, p<.05) only in the high peak VO2 group. Similarly, FNDC5 and PGC-1α gene expression was greater in the high performance group based on lower VE/VCO2 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/VCO2 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.
- Received June 6, 2012.
- Accepted September 4, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited