Metabolic and Barrier Function in Response to β-Caryophyllene in Intestinal Epithelial Cells

Butyrate, a short-chain fatty acid, regulates cellular metabolism and energy status in intestinal epithelial cells. β-caryophyllene (BCP) is a plant-derived compound that may provide advantageous effects on intestinal barrier function and nutrient utilization. The goal of this thesis was to investigate the effects of BCP on butyrate utilization and metabolism in intestinal epithelial cells. Throughout this thesis, Caco-2 cells in hanging inserts in multi-well plates were used as a model for the intestinal barrier. One study was conducted to investigate the effect of BCP on butyrate utilization and barrier function in intestinal epithelial cells. A second study aimed to elucidate the mechanism by which BCP promotes β-hydroxybutyrate (BHB) production. Results from these studies first showed that BCP increases BHB production, butyrate disappearance, and transepithelial electrical resistance in the presence of butyrate. Additionally, these results suggest that BCP acts through the cannabinoid receptor 2, a component of the endocannabinoid system. While the mechanism by which BCP alters cellular metabolism has not been fully elucidated, as these results suggest that peroxisome proliferator receptor (PPARα) is not the key molecular target. Overall, our data provide clear evidence for bioactivity of BCP in intestines, and justification for future investigations into the interaction with the endocannabinoid system, and the potential benefits of BCP in the gastrointestinal tract.