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    Contrôle circadien du métabolisme et de l'inflammation par Rev-erba

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    SÉMINAIRE DE L'INSTITUT COCHIN

    Hélène Duez 

    Hélène Duez

    Univ Lille, Inserm, Institut Pasteur de Lille, EGID, Lille

     

    Jeudi 16 novembre 2017 à 12h00
     

     invitée par Anne-Françoise Burnol & Catherine Postic

     

    Institut Cochin, 22 rue Méchain, 75014 Paris
    Salle de conférence Rosalind Franklin, 2e étage

    Many physiological processes oscillate diurnally under the control of the biological clock. The molecular clock is composed of several transcription factors among which the drug-targetable nuclear receptor Rev-erb-α. Rev-erb-α is implicated in the circadian control of metabolism and Rev-erbα deletion in mice provokes a de-repression of hepatic lipogenesis as well as increased plasma levels of atherogenic lipoprotein particles. Thus, we hypothesized that Rev-erb-α plays a role in the development of atherosclerosis. We discovered that Rev-erbα deletion led to markedly increased atherosclerotic lesion areas due to an inadequate increase of NLRP3. Aberrant activation of the NLRP3 inflammasome is implicated in the pathogenesis of numerous diseases including type 2 diabetes, atherosclerosis, gout, rheumatoid arthritis and kidney diseases, some of which have also been linked to disruption of the clock. Our study points to Reverb-α as a plausible link between a dysregulated clock and NLRP3-driven pathologies and a pharmacological target for NLRP3-dependent inflammatory disorders.

     

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