Date of Award:
Master of Science (MS)
Timothy A. Gilbertson
In recent years, dietary fat has been shown to be capable of activing taste receptor cells in the tongue. Fatty acids (FAs), which act as the chemical cue and are found in dietary fat, activate a cellular signaling pathway that results in a unique signal being sent to the brain that is then interpreted as the taste of fat. One important element in this pathway is the ion channel TrpM5. It is responsible for depolarizing the taste cells that are activated by fatty acids; depolarization is an essential step in cellular response, making TrpM5 essential in the functioning of the FA signaling pathway.
To study the potential roles of the FA signaling pathway, a mouse model, in which mice lacked the TrpM5 gene (TrpM5-/-), was used. From this model, I show that TrpM5 is essential for detection of fatty acids in the oral cavity; without TrpM5, mice were not able to detect FAs in the mouth. I also show here that TrpM5-/- mice eat significantly less and gain significantly less weight on a high fat diet than wildtype mice, who have the TrpM5 gene, linking TrpM5 to both fat intake and weight gain. Interestingly, these responses are only seen in male mice. Females lacking TrpM5 show no deficit in calorie intake compared to the wildtype females. Despite taking in the same amount of calories as the wildtype females, TrpM5-/- females still gain significantly less weight than the wildtypes. This posits a sex-specific response in terms of calorie intake on a high fat diet. Additionally, I show that the TrpM5 pathway is specific for a subtype of fatty acids, primarily the long-chain polyunsaturated fatty acids (PUFAs) and does not contribute to saturated fatty acid taste transduction. Lastly, in this study I show that both male and female mice who do not have TrpM5 excrete significantly less lipids in their feces than the wildtype mice; surprisingly not implicating TrpM5 in fat malabsorption. We are currently looking for other roles of TrpM5 in fat metabolism.
Nelson, Melissa N., "The Role of the Fatty Acid Signaling Pathway in Dietary-Induced Obesity" (2017). All Graduate Theses and Dissertations. 5865.
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