Body weight–dependent alterations in intestinal cannabinoid receptor expression during inflammatory bowel disease and their association with plasma adipokines

In the coexistence of overweight and inflammatory bowel disease (IBD), such as Crohn’s disease and ulcerative colitis, mortality is increased, while the roles of cannabinoid receptors (CB1 encoded by Cnr1, CB2 encoded by Cnr2) remain unexplored. CB1 and CB2 regulate homeostasis and intestinal CB2 signaling has anti-inflammatory effects. Crosstalk between cannabinoid receptors and adipokines (leptin, adiponectin and resistin) has been reported; however it is unexplored in IBD. We aimed to investigate whether intestinal Cnr1 and Cnr2 expressions are differentially regulated according to body weight and whether their expression correlates with adipokine levels during IBD. Participants were stratified by body mass index and IBD status into four groups (Approved by the HU-UFJF Ethics Committee n^o 7.021.975): normal-weight controls (NW, n = 23), normal-weight participants with IBD (NW+IBD, n = 44), overweight controls (OW, n = 22), and overweight participants with IBD (OW+IBD, n = 28). In intestinal and plasma samples were assessed mRNA of Cnr1 and Cnr2 mRNA and adipokines levels. Significant results (p<0.05) were determined using two-way ANOVA followed by Tukey’s test and Spearman’s correlation. OW+IBD group showed decreased (-20%) Cnr2 mRNA in colon. In the ileum, NW+IBD group presented decreased (-33%) Cnr1 mRNA compared to NW, whereas OW+IBD group presented decreased (-56%) Cnr2 mRNA compared to NW.  Regardless IBD, plasma leptin and adiponectin levels were increased (+56%) and decreased (-21%) in the overweight groups, respectively. Independently of body weight, plasma resistin levels were upregulated (+25%) in IBD groups. However, plasma resistin levels were positively correlated (r= 0.810) with ileal Cnr2 mRNA only in OW+IBD. In conclusion, in OW+IBD group, intestinal Cnr2 expression was downregulated and positively correlated with resistin levels. These findings support a possible role for CB2 as a modulator of inflammatory responses in obesity-associated IBD.