title: Resveratrol prevents the wasting disorders of mechanical unloading by acting as a physical exercise mimetic in the rat.
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 long-term 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.
authors.affiliation: Unité Mixte de Recherche 7178, Centre National de la Recherche Scientifique, Institut Pluridisciplinaire Hubert Curien, Université de Strasbourg, Strasbourg, France.
authors.forename: Iman
authors.initials: I
authors.lastname: Momken
authors.forename: Laurence
authors.initials: L
authors.lastname: Stevens
authors.forename: Audrey
authors.initials: A
authors.lastname: Bergouignan
authors.forename: Dominique
authors.initials: D
authors.lastname: Desplanches
authors.forename: Floriane
authors.initials: F
authors.lastname: Rudwill
authors.forename: Isabelle
authors.initials: I
authors.lastname: Chery
authors.forename: Alexandre
authors.initials: A
authors.lastname: Zahariev
authors.forename: Sandrine
authors.initials: S
authors.lastname: Zahn
authors.forename: T Peter
authors.initials: TP
authors.lastname: Stein
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Sebedio
authors.forename: Estelle
authors.initials: E
authors.lastname: Pujos-Guillot
authors.forename: Maurice
authors.initials: M
authors.lastname: Falempin
authors.forename: Chantal
authors.initials: C
authors.lastname: Simon
authors.forename: Véronique
authors.initials: V
authors.lastname: Coxam
authors.forename: Tany
authors.initials: T
authors.lastname: Andrianjafiniony
authors.forename: Guillemette
authors.initials: G
authors.lastname: Gauquelin-Koch
authors.forename: Florence
authors.initials: F
authors.lastname: Picquet
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanc
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001682:Biological Availability; D015415:Biomarkers / Q000097:blood; D001833:Body Temperature Regulation / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D019417:Hindlimb Suspension; D007249:Inflammation / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects; D009133:Muscular Atrophy / Q000188:drug therapy; D010805:Physical Conditioning, Animal; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000652:urine
chemical_list: D015415:Biomarkers; D004791:Enzyme Inhibitors; D013267:Stilbenes; D000077185:Resveratrol