Date of Award:

5-2016

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Biology

Advisor/Chair:

Timothy A. Gilbertson

Abstract

Previous research has shown the gustatory recognition of the long-chain unsaturated fatty acids. In this study, I showed for the first time that medium-chain saturated fatty acids (MCFAs) are effective taste stimuli at both the cellular and behavioral levels. The mechanisms of gustatory recognition of MCFAs in mice were also partially elucidated using pharmaceutical approaches. The inward currents induced by capric acid in mouse taste cells were significantly inhibited by the antagonists of G-protein signaling, protein kinase A (PKA), and protein kinase C (PKC), but they were not affected by the phospholipase C (PLC) and phosphodiesterase (PDE) inhibitors, which suggested that MCFA taste transduction involves G-protein, PKA, and PKC activation, but does not involve PLC and PDE. Furthermore, transient receptor potential channel type M5 (TRPM5) knockout mice showed unaffected cellular and behavioral responses, indicating MCFA taste transduction in mice was TRPM5-independent. The receptor of MCFAs on taste cells was also investigated in this study. Previous research has shown that GPR84 is a novel G protein-coupled receptor (GPCR) activated by MCFAs with 9 to 14 carbons, and the real-time PCR results supported the mRNA expression of GPR84 in mouse taste cells. Therefore, GPR84 is a good candidate for the MCFA receptor in taste cells. By using a cell line that had an inducible GPR84 + Gqi9 (a chimeric G-protein), ligand specificity experiments showed that the ligands of GPR84 included saturated fatty acids with 6 to 12 carbons and other fatty acids (oleic acid, arachidic acid) previously not known to activate this receptor. Compared to wild type cells, taste cells lacking GPR84 showed significantly lower calcium responses and inward currents to capric acid (C10), and GPR84 knockout mice showed decreased taste sensitivities to both lauric (C12) and capric acids behaviorally, suggesting that GPR84 plays an essential role in MCFA taste transduction process.

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