Taste contributes to quality of life and healthy eating habits, aiding with the recognition of nutrients in food. The underlying molecular and cellular mechanisms responsible for transducing the taste of saccharides (sweet), amino acids (umami), and sodium (salty) have been characterized, but those responsible for detecting fat are controversial. Our preliminary studies indicate that an orphan G protein-coupled receptor, GPR113, is a bona fide fat taste receptor, and that the G? protein GNA14 transduces the fat taste signal from GPR113. Moreover, we have identified a subset of T1R+ taste cells expressing GPR113 and GNA14 that support fat taste. We propose to elucidate the roles of GPR113 and GNA14 in T1R+ taste cells.
In Aim 1, we will record the behavioral and electrophysiological responses elicited by fat taste stimuli in Gpr113 knockout (KO) and Gna14 KO mice.
In Aim 2, we will use a cell-based assay to deorphanize GPR113 and evaluate the contribution of GNA14 and T1Rs to the GPR113-dependent transduction pathway.
In Aim 3, we will study the role of a transcription factor, FOXA2, that we hypothesize regulates the differentiation of fat taste cells. Knowledge obtained from this research will improve our understanding of the taste of fat and provide an opportunity to consider fat as a basic taste. As part of the project, we will establish a cell-based assay to screen for GPR113 modulators, which could potentially help develop fat taste enhancers that will allow us to reduce fat contents in our diets.

Public Health Relevance

Overconsumption of fat contributes to obesity and its related health problems. Fat is detected by taste and somatosensory systems, but its receptor mechanism is controversial, especially in taste. We propose to conduct behavioral, electrophysiological, and molecular genetic and biochemical studies to characterize a putative fat taste receptor, GPR113; a fat taste transducer, GNA14; and a transcription factor regulating fat taste cell differentiation, FOXA2, which could help develop fat taste enhancers to reduce fat content in our diets.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
1R01DC017503-01
Application #
9643092
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
2018-12-01
Project End
2023-11-30
Budget Start
2018-12-01
Budget End
2019-11-30
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Monell Chemical Senses Center
Department
Type
DUNS #
088812565
City
Philadelphia
State
PA
Country
United States
Zip Code
19104