Cannabinoid receptor 1 blockade attenuates metabolic inflammation and gut microbial dysbiosis during high-fat diet-induced obesity.

• DOI: 10.4049/jimmunol.200.supp.117.31
• Publication Date: 2023-01-01T11:30:47Z
• Authors: Kathryn Miranda; William J Becker; Philip Brandon Bu...; Lorenzo Menzel; Nicholas Dopkins; Prakash S Nagarkatti; Mitzi Nagarkatti
• Keywords: Dysbiosis; Diet-induced obese

Abstract The endocannabinoid (eCB) system regulates a variety of physiological processes including inflammation and metabolism. Obesity is characterized by overactivation the eCB system, chronic low-grade inflammation, metabolic dysfunction, gut microbial dysbiosis. Blockade cannabinoid receptor 1 (CB1) ameliorates obesity, however CB1-mediated immune-microbial interactions have not been extensively explored. In current study, antagonists genetic ablation CB1 were used in mouse model diet-induced obesity to determine role modulating metabolism, microbiome. As expected, CB1−/− mice resistant high-fat diet (HFD)-induced weight gain was significantly less when compared wild-type (WT) controls. Lamina propria lymphocytes from did display Th1 induction after HFD feeding whereas WT fed had elevated CD4+T-bet+ cells low-fat diet. Decreased colonic indicated CB1-dependent alterations microbiome may contribute decreased obese phenotype. Similarly, treated with antagonist AM251 experienced loss, improvement parameters. Interrogation 16S metagenomics revealed abundance bacteria belonging Clostridiales order. addition, functional predictions PICRUSt analysis operational taxonomic units bacterial metabolism membrane transport pathways. Together these data suggest shaping immune response community.