The endocannabinoid system links gut microbiota to adipogenesis.
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(1) 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 in vivo and ex vivo 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.
Muccioli
Giulio G
GG
Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium. giulio.muccioli@uclouvain.be
Naslain
Damien
D
Bäckhed
Fredrik
F
Reigstad
Christopher S
CS
Lambert
Didier M
DM
Delzenne
Nathalie M
NM
Cani
Patrice D
PD
D050156:Adipogenesis / Q000187:drug effects; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D018988:Bacterial Translocation / Q000187:drug effects; D018938:Caco-2 Cells; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D004195:Disease Models, Animal; D013759:Dronabinol / Q000031:analogs & derivatives / Q000494:pharmacology; D063388:Endocannabinoids; D005989:Glycerides / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000382:microbiology*; D008070:Lipopolysaccharides / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics; D009765:Obesity / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D010539:Permeability; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D056692:Prebiotics; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000077285:Rimonabant
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D056692:Prebiotics; D011720:Pyrazoles; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D013759:Dronabinol; C094503:glyceryl 2-arachidonate; C062018:HU 211; D000077285:Rimonabant; C078814:anandamide