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6. CONCLUSIONS ET PERSPECTIVES
6. CONCLUSIONS ET PERSPECTIVES
Au cours de ce travail, nous avons confirmé que l’efficacité de la chirurgie bariatrique en terme pondéral et métabolique est multifactorielle. Nous avons identifié le rôle majeur de la perte de poids après chirurgie bariatrique dans l’amélioration du métabolisme glucidique et des paramètres métaboliques. Nous avons également déterminé l’impact positif de la masse musculaire initiale sur la perte de poids après chirurgie, facteur également déterminant dans le contrôle du métabolisme glucidique. Les marqueurs du dysfonctionnement cellulaire Beta sont également apparus déterminants pour prédire le succès métabolique et notamment la rémission du diabète de type 2 après chirurgie. Ainsi, l’efficacité de la chirurgie dans le contrôle du syndrome métabolique, au-delà de la technique opératoire, apparaît très dépendante de la perte de poids mais aussi du terrain, confirmant l’importance du phénotypage de l’obésité en préopératoire. Caractériser l’obésité et son retentissement métabolique semble déterminant pour adapter au mieux la technique opératoire au cas par cas afin d’optimiser les résultats.
Le tissu adipeux est apparu comme un élément clé du phénotype d’obésité, avec un rôle direct dans la régulation du métabolisme lipidique et glucidique au niveau hépatique et musculaire. La constitution de la tissuthèque DioMede et l’obtention de milieux conditionnés de tissu adipeux nous ont permis d’étudier l’impact de ce tissu adipeux sur les tissus insulino-sensibles en se rapprochant des conditions physiologiques. Nous avons pu identifier l’impact direct du tissu adipeux sur le métabolisme musculaire par le biais des AG. Nos résultats confirment le rôle régulateur négatif des AGI sur SREBP-1c et ont permis de préciser leur mode d’action qui se situe au niveau transcriptionnel, conduisant à une baisse des cibles transcriptionnelles de SREBP-1c, et à une moindre lipogenèse dans les cellules musculaires.
La proportion et la sécrétion d’AGI et AGS par le tissu adipeux apparaissent donc comme déterminantes dans la régulation de la lipogenèse des tissus insulino-sensibles (foie et muscle), et pourrait être le reflet des obésités avec désordres métaboliques.
La proportion d’AGS contenue et sécrétée par le tissu adipeux pourrait être un marqueur d’insulino-résistance et de stéatose notamment au niveau du foie. L’augmentation de la proportion d’AGPI par supplémentation orale apparaît d’ailleurs déjà comme un objectif thérapeutique notamment pour le traitement de la stéatose hépatique.
La supplémentation en AGPI pourrait, dans un avenir proche, être recommandée à plus large échelle, aux patients obèses, comme un traitement améliorant l’insulino-résistance et protecteur contre les désordres métaboliques et la survenue du DT2.
115 Afin d’étudier l’impact réel du régime alimentaire sur la composition du tissu adipeux et sur ses sécrétions et par conséquent sur le métabolisme musculaire et hépatique, nous testerons l’effet des sérums des patients prélevés avant régime substitué en AGPI (Omacor®) puis leur effet après régime sur la régulation de SREBP-1. Nous avons ainsi l’objectif de développer une sérothèque incluant à la foi des patients opérés d’obésité mais également des patients pris en charge médicalement dans le cadre d’un syndrome métabolique ou d’un diabète. Ce projet devrait être facilité par l’intégration du pôle recherche et des pôles médicaux et chirurgicaux au sein d’une Fédération Hospitalo-Universitaire (FHU DO-IT) destinée à harmoniser et faciliter la collaboration autour de l’obésité et ses conséquences métaboliques.
Une prochaine étape de nos recherches sera également la caractérisation des AGI impliqués dans la régulation du métabolisme des AG au niveau musculaire par une approche lipidomique approfondie au niveau des tissus adipeux (viscéral et sous-cutané), des MC et du sérum des sujets sources.
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