The Role of TRPM5 in Dietary Fat Preference, Intake, and Body Composition

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 ...