Interactions of Estrogen and TRPM5 Channels in Fat Taste and Metabolism

Abstract

Transient Receptor Potential channel type Melastatin 5 (TRPM5) is a nonselective cation channel that is activated by an increase in cytosolic calcium. TRPM5 channels are highly expressed in Type II taste receptor cells that transduce bitter, sweet, umami, and fatty acid compounds. While the function of TRPM5 channels is well‐defined in these cells, the effects of hormones such as estrogen on TRPM5‐mediated signaling that impact the taste system are not well known. We investigated TRPM5 channel activation in fatty acid‐sensing cells and the physiological impact in long‐term fat intake in males and females. This study followed from our earlier work where we showed a sex difference in TRPM5‐deficient (TRPM5−/−) animals and their wild type (WT) counterparts on a 60% high‐fat diet. We showed TRPM5−/− male mice were obese‐resistant compared to their WT counterparts. In comparison, TRPM5−/− females showed no drastic change in caloric intake but gained less body weight and body fat compared to the WT females. We found that removing the secretion of estrogen via ovariectomy in the TRPM5−/− females changed their weight status; they gained the same amount of weight and body fat as the WT females while not altering their caloric intake. At the taste cell level, we found that estrogen increased fatty acid‐induced Ca2+ responses in both TRPM5−/− and their WT counterparts. Interestingly, this difference was papillae‐specific in the TRPM5−/− females; circumvallate taste cells showed no increase in fatty acid responses when estrogen was present. Fungiform taste cells displayed a striking increase in cytosolic calcium in TRPM5−/− but not in WT females. Together, these results demonstrate a link between estrogen and TRPM5‐mediated signaling in feeding behavior and taste cells that is both sex and papillae‐specific. We are conducting additional experiments to better understand the mechanistic interactions between estrogen receptor activation and taste signaling via TRPM5 channels.Support or Funding InformationSupported by NIH DC013194 and DC013318 (tag)