Resveratrol prevents the wasting disorders of mechanical unloading by acting as a physical exercise mimetic in the rat

Iman Momken, Laurence Stevens, Audrey Bergouignan, Dominique Desplanches, Floriane Rudwill, Isabelle Chery, Alexandre Zahariev, Sandrine Zahn, T. Peter Stein, Jean Louis Sebedio, Estelle Pujos-Guillot, Maurice Falempin, Chantal Simon, Veŕonique Coxam, Tany Andrianjafiniony, Guillemette Gauquelin-Koch, Florence Picquet, Steṕhane Blanc

Research output: Contribution to journalArticlepeer-review

118 Scopus citations

Abstract

Long-term spaceflight induces hypokinesia and hypodynamia, which, along microgravity per se, result in a number of significant physiological alterations, such as muscle atrophy, force reduction, insulin resistance, substrate use shift from fats to carbohydrates, and bone loss. Each of these adaptations could turn to serious health deterioration during the longterm spaceflight needed for planetary exploration. We hypothesized that resveratrol (RES), a natural polyphenol, could be used as a nutritional countermeasure to prevent muscle metabolic and bone adaptations to 15 d of rat hindlimb unloading. RES treatment maintained a net protein balance, soleus muscle mass, and soleus muscle maximal force contraction. RES also fully maintained soleus mitochondrial capacity to oxidize palmitoyl- carnitine and reversed the decrease of the glutathione vs. glutathione disulfide ratio, a biomarker of oxidative stress. At the molecular level, the protein content of Sirt-1 and COXIV in soleus muscle was also preserved. RES further protected whole-body insulin sensitivity and lipid trafficking and oxidation, and this was likely associated with the maintained expression of FAT/CD36, CPT-1, and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in muscle. Finally, chronic RES supplementation maintained the bone mineral density and strength of the femur. For the first time, we report a simple countermeasure that prevents the deleterious adaptations of the major physiological functions affected by mechanical unloading. RES could thus be envisaged as a nutritional countermeasure for spaceflight but remains to be tested in humans.

Original languageEnglish (US)
Pages (from-to)3646-3660
Number of pages15
JournalFASEB Journal
Volume25
Issue number10
DOIs
StatePublished - Oct 2011

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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