Hypertrophy of rat skeletal muscle is associated with increased sirt1/akt/mtor/s6 and suppressed sestrin2/sirt3/foxo1 levels

Zoltan Gombos, Erika Koltai, Ferenc Torma, Peter Bakonyi, Attila Kolonics, Dora Aczel, Tamas Ditroi, Peter Nagy, Takuji Kawamura, Zsolt Radak*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Despite the intensive investigation of the molecular mechanism of skeletal muscle hypertrophy, the underlying signaling processes are not completely understood. Therefore, we used an overload model, in which the main synergist muscles (gastrocnemius, soleus) of the plantaris muscle were surgically removed, to cause a significant overload in the remaining plantaris muscle of 8‐ month‐old Wistar male rats. SIRT1‐associated pro‐anabolic, pro‐catabolic molecular signaling pathways, NAD and H2S levels of this overload‐induced hypertrophy were studied. Fourteen days of overload resulted in a significant 43% (p < 0.01) increase in the mass of plantaris muscle compared to sham operated animals. Cystathionine‐β‐synthase (CBS) activities and bioavailable H2S levels were not modified by overload. On the other hand, overload‐induced hypertrophy of skeletal muscle was associated with increased SIRT1 (p < 0.01), Akt (p < 0.01), mTOR, S6 (p < 0.01) and suppressed sestrin 2 levels (p < 0.01), which are mostly responsible for anabolic signaling. Decreased FOXO1 and SIRT3 signaling (p < 0.01) suggest downregulation of protein breakdown and mitophagy. Decreased levels of NAD+, sestrin2, OGG1 (p < 0.01) indicate that the redox milieu of skeletal muscle after 14 days of overloading is reduced. The present investigation revealed novel cellular interactions that regulate anabolic and catabolic processes in the hypertrophy of skeletal muscle.

Original languageEnglish
Article number7588
JournalInternational journal of molecular sciences
Issue number14
Publication statusPublished - 2021 Jul 2


  • Anabolic signaling pathways
  • Overload‐induced hypertrophy
  • Redox regulation
  • Skeletal muscle

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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