Obesity is associated with a cluster of metabolic disorders, chronic low-grade
inflammation, altered gut microbiota, increased intestinal permeability, and alterations of the
lipid mediators of the expanded
endocannabinoid (eCB) signaling system, or endocannabinoidome (eCBome). In the present study, we characterized the profile of the eCBome and related
oxylipins in the small and large intestines of genetically obese (ob/ob) and diabetic (db/db) mice to decipher possible correlations between these mediators and intestinal
inflammation and gut microbiota composition. Basal
lipid and gene expression profiles, measured by LC/MS-MS-based targeted lipidomics and qPCR transcriptomics, respectively, highlighted a differentially altered intestinal eCBome and
oxylipin tone, possibly linked to increased
mRNA levels of inflammatory markers in db/db mice. In particular, the duodenal levels of several 2-monoacylglycerols and
N-acylethanolamines were increased and decreased, respectively, in db/db mice, which displayed more pronounced intestinal
inflammation. To a little extent, these differences were explained by changes in the expression of the corresponding metabolic
enzymes. Correlation analyses suggested possible interactions between eCBome/
oxylipin mediators,
cytokines, and bacterial components and bacterial taxa closely related to intestinal
inflammation. Collectively, this study reveals that db/db mice present a higher inflammatory state in the intestine as compared to ob/ob mice, and that this difference is associated with profound and potentially adaptive or maladaptive, and partly intestinal segment-specific alterations in eCBome and
oxylipin signaling. This study opens the way to future investigations on the
biological role of several poorly investigated eCBome mediators and
oxylipins in the context of
obesity and diabetes-induced gut
dysbiosis and
inflammation.