Grape polyphenols supplementation reduces muscle atrophy in a mouse model of chronic inflammation.
OBJECTIVE
Polyphenols (PP) have demonstrated beneficial effects on low-grade inflammation and oxidative stress; however, little is known about their effect on highly inflamed muscle. The purposes of this study were (i) to evaluate muscle alteration induced by high-grade inflammation, and (ii) to test the effects of red grape PP supplementation on these alterations.


METHODS
We used a transgenic mice model (transforming growth factor [TGF] mice) to develop a high T cell-dependent inflammation and C57 BL/6 control (CTL) mice model. Skeletal muscles of TGF and CTL mice were investigated for inflammation, atrophy and oxidative stress markers. Isolated mitochondria from hindlimb muscles were used for respiration with pyruvate as substrate and oxidative damages were measured by Western blot. TGF mice were supplemented with a mixture of red grape polyphenols (50 mg/kg/d) for 4 wk. Data were analyzed by one-way analysis of variance (ANOVA) and post hoc Bonferroni's multiple comparison tests.


RESULTS
TGF mice presented skeletal muscle inflammation, oxidative stress, mitochondrial alteration and muscle atrophy. Atrophy was associated with two distinct pathways: (i) one linked to inflammation, NF-κB activation and increased ubiquitin ligase expression, and (ii) one dependent on reactive oxygen species (ROS) production leading to damaged mitochondria accumulation and activation of caspase-9 and 3. Supplementation of TGF mice with a mixture of red grape polyphenols (50 mg/kg/d) for 4 wk improved mitochondrial function and highly decreased caspases activation, which allowed muscle atrophy mitigation.


CONCLUSIONS
These observations suggest that nutritional dosages of red grape polyphenols might be beneficial for reducing skeletal muscle atrophy, even in a high-grade inflammation environment.
UMR CNRS 9214 - Inserm U1046 - PHYMEDEXP - Université de Montpellier, Montpellier, France.
Karen
K
Lambert
UMR CNRS 9214 - Inserm U1046 - PHYMEDEXP - Université de Montpellier, Montpellier, France.
Marjorie
M
Coisy-Quivy
UMR CNRS 9214 - Inserm U1046 - PHYMEDEXP - Université de Montpellier, Montpellier, France.
Catherine
C
Bisbal
UMR CNRS 9214 - Inserm U1046 - PHYMEDEXP - Université de Montpellier, Montpellier, France.
Pascal
P
Sirvent
UMR CNRS 9214 - Inserm U1046 - PHYMEDEXP - Université de Montpellier, Montpellier, France.
Gerald
G
Hugon
UMR CNRS 9214 - Inserm U1046 - PHYMEDEXP - Université de Montpellier, Montpellier, France; CHRU Montpellier, Montpellier, France.
Jacques
J
Mercier
UMR CNRS 9214 - Inserm U1046 - PHYMEDEXP - Université de Montpellier, Montpellier, France; CHRU Montpellier, Montpellier, France.
Antoine
A
Avignon
UMR CNRS 9214 - Inserm U1046 - PHYMEDEXP - Université de Montpellier, Montpellier, France; CHRU Montpellier, Montpellier, France. Electronic address: a-sultan@chu-montpellier.fr.
Ariane
A
Sultan
D000704:Analysis of Variance; D000818:Animals; D020169:Caspases / Q000378:metabolism; D019587:Dietary Supplements; D006614:Hindlimb; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008931:Mitochondria, Muscle / Q000378:metabolism; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000187:drug effects / Q000276:immunology; D009133:Muscular Atrophy / Q000178:diet therapy*; D009220:Myositis / Q000178:diet therapy*; D018384:Oxidative Stress / Q000276:immunology; D059808:Polyphenols / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects; D027843:Vitis / Q000737:chemistry*
D059808:Polyphenols; D020169:Caspases
Caspases; Mitochondria; Muscle atrophy; Oxidative stress; Polyphenols; TGF