The endocannabinoid system links gut microbiota to adipogenesis

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  • Giulio G Muccioli
    Louvain Drug Research Institute, Université catholique de Louvain Brussels Belgium
  • Damien Naslain
    Louvain Drug Research Institute, Université catholique de Louvain Brussels Belgium
  • Fredrik Bäckhed
    Department of Molecular and Clinical Medicine, Sahlgrenska Center for Cardiovascular and Metabolic Research/Wallenberg Laboratory, University of Gothenburg Gothenburg Sweden
  • Christopher S Reigstad
    Department of Molecular and Clinical Medicine, Sahlgrenska Center for Cardiovascular and Metabolic Research/Wallenberg Laboratory, University of Gothenburg Gothenburg Sweden
  • Didier M Lambert
    Louvain Drug Research Institute, Université catholique de Louvain Brussels Belgium
  • Nathalie M Delzenne
    Louvain Drug Research Institute, Université catholique de Louvain Brussels Belgium
  • Patrice D Cani
    Louvain Drug Research Institute, Université catholique de Louvain Brussels Belgium

Description

<jats:p>Obesity is characterised by altered gut microbiota, low‐grade inflammation and increased endocannabinoid (eCB) system tone; however, a clear connection between gut microbiota and eCB signalling has yet to be confirmed. Here, we report that gut microbiota modulate the intestinal eCB system tone, which in turn regulates gut permeability and plasma lipopolysaccharide (LPS) levels. The impact of the increased plasma LPS levels and eCB system tone found in obesity on adipose tissue metabolism (e.g. differentiation and lipogenesis) remains unknown. By interfering with the eCB system using CB<jats:sub>1</jats:sub> agonist and antagonist in lean and obese mouse models, we found that the eCB system controls gut permeability and adipogenesis. We also show that LPS acts as a master switch to control adipose tissue metabolism both <jats:italic>in vivo</jats:italic> and <jats:italic>ex vivo</jats:italic> by blocking cannabinoid‐driven adipogenesis. These data indicate that gut microbiota determine adipose tissue physiology through LPS‐eCB system regulatory loops and may have critical functions in adipose tissue plasticity during obesity.</jats:p>

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