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- W2800841563 abstract "ResumeL'obesite et les maladies metaboliques qui lui sont associees tels que le diabete ou les maladies cardiovasculaires ont un impact epidemiologique croissant. Ainsi, les mecanismes moleculaires se produisant dans le tissu adipeux en expansion font l'objet de nombreuses investigations. Dans ce contexte, nous nous sommes particulierement interesses a l'adipogenese, le procede permettant la formation d'adipocytes matures et fonctionnels. Le gene St3gal6 code pour une enzyme appelee β-galactosidase a2,3-sialyltransferase 6 et participant a la voie de glycosylation. Cette proteine appartient a la famille des a2,3- sialyltransferases dont la fonction principale est de transferer un acide sialique a l'extremite de chaines glycosidiques presentes sur les glycoproteines et les glycolipides. Dans une precedente etude de transcriptomique realisee chez la souris, St3gal6 a ete decrit comme un gene dont l'expression est augmentee dans le tissu adipeux blanc d'animaux en surpoids et dont l'expression est normalisee apres une perte de poids. Afin d'etudier le role potentiel de St3gal6 dans le developpement du tissu adipeux, nous nous sommes interesses a la regulation de son expression en cas d'obesite ainsi qu'a ses effets sur l'adipogenese. Nous avons d'abord montre que St3gal6 s'exprime aussi bien dans le tissu adipeux blanc que dans le tissu adipeux brun. Puis nous avons confirme dans deux differents modeles animaux que l'expression de St3gal6 dans le tissu adipeux etait augmentee en cas d'obesite. Nous avons aussi observe in vitro une induction de St3gal6 dans des adipocytes traites par des cytokines pro-inflammatoires secretees dans le tissu adipeux d'individus obeses. Enfin, parmi les six membres que compte la famille des a2,3-sialyltransferases, St3gal6 est celui dont l'expression est la plus significativement induite en situation d'obesite. En outre, au cours de la differenciation des adipocytes blancs et bruns, l'expression de St3gal6 est augmentee et son inhibition reduit le potentiel de maturation des adipocytes qui accumulent moins de lipides. A l'inverse, la surexpression de St3gal6 dans des preadipocytes blancs augmente leur taux de differenciation in vitro; la formation de gouttelettes lipidiques et l'expression de genes specifiques de l'adipocyte mature sont accrues. Enfin, le traitement d'adipocytes blancs in vitro avec un inhibiteur pharmacologique des a2,3-sialyltransferases ou une sialidase clivant les residus sialyles montre qu'un defaut de a2,3-sialylation affectant les adipocytes diminue leur potentiel adipogenique. Par consequent, ces resultats suggerent que St3gal6 est implique dans la voie de differenciation des adipocytes et que cette a2,3-sialylation joue un role dans le remodelage du tissu adipeux induit par l'obesite.AbstractIn order to better understand molecular events occurring in obesity and leading to its associated complications, we were interested in the biology of adipose tissue and particularly in the study of adipogenesis, the process by which new mature adipocytes develop and accumulate lipids.The β-galactosidase a2,3-sialyltransferase 6 (St3gal6) gene encodes for an enzyme involved in post-translational protein glycosylation. Thereby, St3gal6 enzyme belongs to the a2,3sialyltransferase family whose function is to add sialic acids at outer position on glycosidic chain of glycoproteins or glycolipids. Previously, in mouse, St3gal6 has been described as a gene whose expression in white adipose tissue is increased in overweighted animals and normalized after weight loss. Therefore, we have assumed that St3gal6 may play a role in adipose tissue development and in tissue remodelling triggered by obesity. First we show that St3gal6 is expressed in white but also in brown adipose tissue. St3gal6 upregulation upon weight gain was confirmed in two mouse models of obesity namely diet- induced and genetically-induced obesity. We also report that St3gal6 is induced by pro¬inflammatory cytokines known to be oversecreted in adipose tissue during obesity. Furthermore, St3gal6 is the a2,3-sialyltransferase whose expression is more markedly induced in adipose tissue. In addition, we demonstrate that St3gl6 expression is progressively increased in late stages of white and brown adipogenesis while St3gal6 knockdown inhibits adipocyte differentiation in vitro. Conversely, St3gal6 overexpression in a white preadipocyte cell line increases lipid accumulation during differentiation process and enhances gene expression of mature white adipocyte markers. Finally, using an a2-3 sialyltransferase inhibitor and a sialidase treatment on white adipocyte cell line, we observe that a decreased a2,3-sialylation impairs adipocyte differentiation in vitro. Altogether, these result suggest that St3gal6 plays a role in adipogenesis and in tissue remodelling associated with obesity likely through its enzymatic activity of a2,3-sialylation. Thus, a2,3-sialylation appears as a novel pathway of interest whose precise molecular mechanisms remain to be elucidated in the context of adipose tissue development and adipocyte functions." @default.
- W2800841563 created "2018-05-17" @default.
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- W2800841563 date "2011-01-01" @default.
- W2800841563 modified "2023-09-26" @default.
- W2800841563 title "Study of a sialyltransferase ST3GAL6, in adipogenesis and obesity" @default.
- W2800841563 hasPublicationYear "2011" @default.
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