Premium
FNDC5 expression in skeletal muscle in chronic heart failure: relevance of inflammatory cytokines (704.1)
Author(s) -
Adams Volker,
Gleitsmann Konstanze,
Mangner Norman,
Bowen T Scott,
Schuler Gerhard,
Linke Axel
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.704.1
Subject(s) - fndc5 , medicine , endocrinology , myokine , skeletal muscle , myogenesis , c2c12 , myocyte , muscle atrophy , chemistry , biochemistry , fibronectin , extracellular matrix
Chronic heart failure (CHF) is associated with muscle atrophy. Irisin, a myokine proteolytically processed by the FNDC5 protein and suggested to be PGC‐1α activated, modulates the browning of adipocytes and is related to muscle mass. Therefore, we investigated whether skeletal muscle FNDC5 expression in CHF was reduced and if this was mediated by inflammatory cytokines and/or angiotensin II (Ang‐II). Methods: Skeletal muscle FNDC5 mRNA/protein and PGC‐1α mRNA expression were analyzed in: Rats with CHF; Mice injected with TNF‐α (24h); Mice infused with Ang‐II (4 wk); C2C12 myotubes exposed to recombinant cytokines or Ang‐II. Results: CHF reduced (p<0.05) FNDC5 protein (1.3±0.2 vs. 0.5±0.1 arb. units) and PGC‐1α mRNA expression (8.2±1.5 vs. 4.7±0.7 arb. units) compared to control. TNF‐α and Ang‐II reduced FNDC5 protein by 28% and 45%, respectively. Incubation of myotubes for 24h with a TNF‐α, IL‐1ß, and IFN‐ γ cocktail reduced (p<0.05) FNDC5 protein expression by 71%, whereas Ang‐II had no effect. PGC‐1α was linearly correlated to FNDC5 in all conditions. Conclusion: Skeletal muscle FNDC5 expression is reduced in CHF, which seems mediated by inflammatory cytokines, Ang‐II, and PGC‐1α. This suggests a reduced FNDC5 expression may act as a protective mechanism in catabolic states, by preserving energy homeostasis via slowing the browning of adipocytes.