Sex differences in fat taste responsiveness are modulated by estradiol

Abstract

Sex as a biological variable has been the focus of increasing interest. Relatively few studies have focused, however, on differences in peripheral taste function between males and females. Nonetheless, there are reports of sex-dependent differences in chemosensitivity in the gustatory system. The involvement of endogenous changes in ovarian hormones have been suggested to account for taste discrepancies. Additionally, whether sex differences exist in taste receptor expression, activation and subsequent signaling pathways which may contribute to different taste responsiveness is not well understood. In this study, we show the presence of both the nuclear and plasma membrane forms of estrogen receptor (ER) mRNA and protein in mouse taste cells. Further, we provide evidence that estrogen increases taste cell activation during the application of fatty acids, the chemical cue for fat taste, in taste receptor cells. We found that genes important for the transduction pathway of fatty acids vary between males and females and that these differences also exist across the various taste papillae. In vivo support for the effect of estrogens in taste cells was provided by comparing the fatty acid sensitivity in males, intact females, and ovariectomized (OVX) female mice with and without hormone replacement. In general, females detected fatty acids at lower concentrations and the presence of circulating estrogens increased this apparent fat taste sensitivity. Taken together, these data indicate that increased circulating estrogens in the taste system may play a significant role in physiology and chemosensory cellular activation and, in turn, may alter taste driven behavior.

Ghrelin Receptors Enhance Fat Taste Responsiveness in Female Mice

“…Figure 5B) but does not do so in females (Figure 5A). This suggests that there are significant sex differences in fatty acid taste and its metabolic regulation, a finding that has recently received additional empirical support [33]. Our results in Ghsr −/− mice, coupled with those of Cai et al in ghrelin KO mice [12], may provide further insight into the role ghrelin plays in the taste system and whether it is through the GHS-R signaling pathway or through alternative mechanisms.…”

“…Females responded to lower concentrations of fatty acids than males, while loss of ovarian hormones reversed this effect by decreasing taste responsiveness to fat. Furthermore, fatty acid taste responsiveness varied significantly within the estrous cycle in females, where high levels of taste responsiveness coincided with high secretion of estradiol [33]. Of note, our CTA experiments illustrated similar fat taste thresholds between WT males and females, whereas significant differences were observed in previous studies [33,37].…”

“…In one crowdsourcing human study, women and girls rated high concentrations of LA as more intense than men and boys [36]. Recently, it was shown that there are sex differences in fat taste detection and that estradiol acts as the key regulator in altering fatty acid taste responsiveness [33]. Females responded to lower concentrations of fatty acids than males, while loss of ovarian hormones reversed this effect by decreasing taste responsiveness to fat.…”

“…Furthermore, fatty acid taste responsiveness varied significantly within the estrous cycle in females, where high levels of taste responsiveness coincided with high secretion of estradiol [33]. Of note, our CTA experiments illustrated similar fat taste thresholds between WT males and females, whereas significant differences were observed in previous studies [33,37]. A question of physiological interest is whether taste responsiveness is altered during the estrous cycle; therefore, it is possible that both the high-fat diet in our experiments and estrous cycle variation complicate apparent fat taste thresholds and contribute to these differences.…”

“…Moreover, GHS-R and estrogen receptor (ERα) are highly co-expressed in a number of hypothalamic regions, indicating a dual role of GHSR and ERα in mediating metabolic signals [40]. ERα is also expressed in taste cells [33], and it is possible that estradiol signaling through ERα is convergent with GHS-R signaling in the taste system. These data help further elucidate the peripheral role of ghrelin in the taste system, likely linked to sex-dependent fatty acid taste pathways.…”