Fasting drives nrf2-related antioxidant response in skeletal muscle

Daniele Lettieri-Barbato, Giuseppina Minopoli, Rocco Caggiano, Rossella Izzo, Mariarosaria Santillo, Katia Aquilano, Raffaella Faraonio

Research output: Contribution to journalArticlepeer-review


A common metabolic condition for living organisms is starvation/fasting, a state that could play systemic-beneficial roles. Complex adaptive responses are activated during fasting to help the organism to maintain energy homeostasis and avoid nutrient stress. Metabolic rearrangements during fasting cause mild oxidative stress in skeletal muscle. The nuclear factor erythroid 2-related factor 2 (Nrf2) controls adaptive responses and remains the major regulator of quenching mechanisms underlying different types of stress. Here, we demonstrate a positive role of fasting as a protective mechanism against oxidative stress in skeletal muscle. In particular, by using in vivo and in vitro models of fasting, we found that typical Nrf2-dependent genes, including those controlling iron (e.g., Ho-1) and glutathione (GSH) metabolism (e.g., Gcl, Gsr) are induced along with increased levels of the glutathione peroxidase 4 (Gpx4), a GSH-dependent antioxidant enzyme. These events are associated with a significant reduction in malondialdehyde, a well-known by-product of lipid peroxidation. Our results suggest that fasting could be a valuable approach to boost the adaptive anti-oxidant responses in skeletal muscle.

Original languageEnglish
Article number7780
Pages (from-to)1-12
Number of pages12
JournalInternational Journal of Molecular Sciences
Issue number20
Publication statusPublished - Oct 2 2020


  • Lipid peroxides
  • Metabolism
  • Nrf2
  • Nutrient restriction
  • Oxidative stress

ASJC Scopus subject areas

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


Dive into the research topics of 'Fasting drives nrf2-related antioxidant response in skeletal muscle'. Together they form a unique fingerprint.

Cite this