Author ORCID Identifier

https://orcid.org/0009-0005-5294-3793

Date Available

10-1-2025

Year of Publication

2025

Document Type

Master's Thesis

Degree Name

Master of Science (MS)

College

Agriculture, Food and Environment

Department/School/Program

Animal and Food Sciences

Faculty

Dr. David Harmon

Faculty

Dr. James Klotz

Abstract

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.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2025.464

Funding Information

This research was supported in part by an appointment to the Agricultural Research Service (ARS) Research Participation Program administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy (DOE) and the U.S. Department of Agriculture (USDA). ORISE is managed by ORAU under DOE contract number DE-SC0014664. All opinions expressed in this paper are the author's and do not necessarily reflect the policies and views of USDA, DOE, or ORAU/ORISE. This study was supported by USDA-ARS National Program 215 – Grass, Forage, and Rangeland Agroecosystems, Project Plan Number: 5042-21000-005-000D

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