The endocannabinoid system links gut microbiota to adipogenesis

Abstract

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.

Fetal endocannabinoids orchestrate the organization of pancreatic islet microarchitecture

“…This observation argues against transdifferentiation as a mechanism eliciting altered islet architecture in MAGL −/− mice. Because eCBs modulate cell migration and survival in the nervous system, adipose tissue, muscle, and immune system (13,22,(28)(29)(30)(31)(32), we instead favor that altered cell migration could, at least in part, contribute to incomplete cell segregation in MAGL −/− mice (Fig. S3).…”

The endocannabinoid system in inflammatory bowel diseases: from pathophysiology to therapeutic opportunity

“…An intriguing observation is the modulation of cannabinoid receptors expression by gut microflora [31,32]. For instance, administration of Lactobacillus acidophilus increases CB 2 expression, resulting in analgesic functions in the gut, a response reversed by the CB 2 receptor antagonist AM630 [32].…”

Impact of the Gut Microbiota on the Development of Obesity: Current Concepts

“…Th is CD14-driven eff ect is paralleled by decreased intestinal permeability and reductions in glucose intolerance, by body weight gain and fat mass development, and by markers of infl ammation, oxidative stress, and infi ltration of macrophages into visceral adipose tissue ( 27 ). Th ese eff ects appear to be mediated, at least in part, by interactions between LPS and adipose tissue metabolism through endocannabinoid-driven adipogenesis ( 28 ).…”