A number of studies have demonstrated the ability of free fatty acids to activate taste cells and elicit behavioral responses consistent with there being a taste of fat. Here I show for the first time that long chain unsaturated free fatty acid, linoleic acid, depolarizes taste cells and elicits a robust intracellular calcium rise via the activation of transient receptor potential channel type M5. The linoleic acid-induced responses depend on G protein-phospholipase C pathway indicative of the involvement of G protein-coupled receptors in the transduction of fatty acids. Mice lacking transient receptor potential channel type M5 exhibit no preference for and show reduced sensitivity to linoleic acid. Together, these studies show that transient receptor potential channel type M5 plays an essential role in fatty acid transduction and suggest that fat may reflect a bona fide sixth primary taste. Studies to identify the types of taste cells that respond to fatty acids show that both type II and type III taste cells express fatty acid-activated receptors. Fatty acids elicit robust intracellular calcium rise primarily in type II taste cells and a subset of type III taste cells. However, a significant subset of type II taste cells respond to high potassium chloride, which has been broadly used as the indicator for type III taste cells as well, suggesting the expression of voltage-gated calcium channels in these cells. This finding conflicts with previous studies that type II taste cells lack voltage-gated calcium channels. To explore if voltage-gated calcium channels are expressed in subsets of type II taste cells, transgenic mice with type II or III taste cells marked by green fluorescent proteins are used. Results show that a subset of type II taste cells exhibit voltage-gated calcium currents, verifying the expression of voltage-gated calcium channels in these cells. These results question the utility of being able to use high potassium chloride solution to identify unequivocally type III taste cells within the taste buds. A model for the transduction of fatty acids in taste cells consistent with these findings and our previous data is presented.

We recently showed a critical role of Trpm5 in the transduction pathway for long chain polyunsaturated fatty acids. In the present study, I have begun to investigate dietary fat preference and the propensity to develop dietary-induced obesity in Trpm5-/- mice. My preliminary data shows that in male mice placed on a high fat diet, Trpm5-/- mice did not enhance their caloric intake as observed in wild type mice. Most surprisingly, however, was that I did not observe the same differences in between female mice, which posits a potential gender effect of this pathway on dietary fat intake. Also, I show that the preference for dietary fat is not disrupted in Trpm5-/- mice since there is no difference in dietary fat preference between Trpm5-/- and wild type mice. Wild type and Trpm5-/- mice both have a strong preference for the high fat diet, as demonstrated by the fact that they solely consumed the high fat diet. Consistent with our original hypothesis that these responses are specific for high fat feeding, I did not observe any differences in caloric intake in male mice on a high sucrose diet. Again, gender differences were observed, with Trpm5-/- female mice displaying a higher caloric intake than wild type female mice. Furthermore, I used a paired-feeding approach via oral gavage to delve further into whether the effect of Trpm5 disruption was due to pre- or post-ingestive effects. The results from this experiment show that all animals have a reduction in body weight and body fat with no significant difference between wild type and Trpm5-/- mice. This result suggests that the expression of Trpm5 in the oral cavity is necessary for the changes in body weight and composition observed during ad libitum feeding. Also, the fact that Trpm5-/- mice lost body weight and fat mass is contrary to our previous observations. When these animals consume the roughly same number of calories on a high fat diet ad libitum, we observe an increase in body weight and fat mass. This suggests that there might be another mechanism accountable for the response observed in Trpm5-/- mice when fed ad libitum. In conclusion, the results from these experiments suggest a link between dietary fat consumption and development of adiposity.