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, RESUME

, Notre but est d'explorer leurs contributions relatives en comparant un modèle associant obésité et conditions métaboliques avec un modèle mimant le surpoids de l'obésité par exposition à une hypergravité. L'obésité MM (mécanique et métabolique) est obtenue par un régime alimentaire qui débute chez des C57BL6/J mâles de 5 semaines. L'obésité M (mécanique) est mimée par une exposition continue à une hypergravité à 2g qui débute à l'âge de 16 semaines. L'arthrose (OA) est induite à l'âge de 16 semaines par déstabilisation du ménisque médial de la patte postérieure droite, L'obésité et le syndrome métabolique sont tous deux associés à un risque de fragilité musculo-squelettique, en particulier d'arthrose

, Les obèses MM ont un os (tibia proximal droit) trabéculaire préservé, un os cortical plus fin et moins poreux et des muscles (tibialis, gastrocnémien, soléaire) fragilisés (diminution de la masse, de la force globale, augmentation du nombre de fibres avec gouttelettes lipidiques). A l'opposé chez les obèses M, l'os est préservé et les muscles sont renforcés (gain de masse, fibres du gastrocnémien plus orientées vers un profil oxydatif lent, stimulation des voies de signalisation), Nous avons tout d'abord exploré les effets des obésités MM et M sur le système musculo-squelettique de souris non arthrosiques

, OA chez les non obèses fragilise l'os trabéculaire de la métaphyse tibiale (et augmente la résorption ostéoclastique) mais n'a aucun effet significatif ni sur l'os cortical, ni sur les muscles adjacents à l'articulation arthrosique. L'OA chez les obèses MM accentue la diminution de l'épaisseur corticale tout en augmentant sa porosité et n'induit pas de détériorations supérieures à celles de l'obésité MM seule pour les autres paramètres. L'OA chez les souris obèses M fragilise encore plus l'os cortical et le muscle que chez les souris MM, Dans une deuxième partie, les conséquences de l'OA sont évaluées chez des souris non obèses, obèses MM ou M. L'

, dernières semaines (entre l'âge de 20 et 24 semaines) comme traitement potentiel des détériorations musculo-squelettiques de l'obésité MM couplée ou non à l'OA. Les vibrations n'impactent pas la sévérité de l'obésité ou de l'arthrose. Un effet musculaire est observé au niveau moléculaire : diminution de l'expression de la myostatine et de son récepteur Act RIIb, de la visfatine, de FNDC5, PPAR-? et CEBP-?, ces diminutions étant plus importantes chez les OA. Toutefois aucun changement de masse musculaire, aire et typage des myofibres n'est observé. Le tissu osseux n'est pas influencé. Ce traitement est donc neutre pour l'os et semble amorcer un effet positif sur le muscle. Les modalités du régime vibratoire, Dans une dernière partie nous avons testé les vibrations corps entiers (90Hz, 0.5g, 15 min/jour, 5 jours/7) pendant les, vol.4

, Par contre chez les OA, l'impact mécanique s'ajoute à l'impact métabolique pour augmenter la fragilité de l'os cortical. L'obésité MM est délétère pour les muscles avec ou sans OA. Les troubles métaboliques s'accompagnent d'un défaut de vascularisation et d'une augmentation de l'adiposité dans l'os et le muscle. L'hypergravité à 2g (obésité M) corrige l'invasion graisseuse musculaire chez les non OA et OA, et médullaire chez les non OA seulement, chez les souris non OA, seuls les troubles métaboliques diminuent l'épaisseur corticale