Biology subjects

Gilbertson, T. A.

Publications and source records attributed to Gilbertson, T. A..

3 recordsLinked to original sources

bioRxiv2025

Estrogen Dependent Variation in the Contributions of TRPM4 and TRPM5 to Fat Taste

Sex differences in physiology have garnered significant interest of late; however, comparatively little is known about the effects of sex on the function of the peripheral taste system. Previously, we have shown that fat taste functions in a sexually dimorphic manner using molecular, cellular, and behavioral assays, and that a subtype of estrogen receptor (ER) proteins are highly expressed in Type II (receptor) cells. The underlying mechanisms of estrogens action, though, remain unknown. Here, we sought to better understand estrogens role in fat taste transduction at the molecular level by initially focusing on the transient receptor potential channels types M4 (Trpm4) and M5 (Trpm5), which we have shown to play roles in estrogen-sensitive fatty acid signaling in taste cells. That is, using Trpm5-deficient mice, both males and females in the estrus phase showed significantly reduced FA responses, whereas females in the proestrus phase did not, suggesting that there may be E2-dependent TRPM5-independent FA signaling in Type II cells. During periods of high levels of circulating estrogen, there was no significant difference in cellular responses to fatty acid (FA) stimuli between Trpm5-/- mice and their wild-type counterparts. Moreover, supplemental estradiol enhanced linoleic acid (LA)-induced TRPM5- mediated taste cell activation. Finally, while Type II cells depend on TRPM4 and TRPM5 for FA taste cell activation, proestrus (high estrogen) females showed a greater dependence on a TRPM5-independent pathway for fatty acid responsiveness. Together, these results underscore the substantial regulatory role of estrogen in the taste system, particularly for fatty acid signaling. Given that the taste system guides food preferences and intake, these findings may have important implications for understanding sex-specific differences in diet and, ultimately, metabolic health. SUMMARYThe current manuscript shows sex differences in fat taste signaling and identifies functional variations in specific transduction elements in taste cells that respond to sex hormones, such as estrogen, that may mediate differences in peripheral fat taste pathways.

neuroscience↗

bioRxiv2025

Fat taste responsiveness, but not dietary fat intake, is affected in Adipor1 null mice

Taste is a major driving force that influences food choices and dietary intake. Adiponectin has been shown to selectively enhance cellular responses to fatty acids by mediating the activation of AMPK and translocation of CD36 in taste cells via its receptor AdipoR1. Whether Adipor1 gene knockout affects fat taste responsiveness and dietary fat intake in animals remains unclear. In the present study, we evaluated cellular, neural, and behavioral responses to fat, as well as the dietary fat intake in global Adipor1 knockout mice and their WT controls. Sex-specific changes in cellular and behavioral responses to fatty acid were observed in Adipor1 knockout mice. Linoleic acid (LA)-induced calcium responsiveness appears to be reduced in taste cells from Adipor1-deficient males and increased in taste cells from Adipor1-deficient females. Brief-access taste testing revealed a loss of fat taste behavioral responsiveness in naive Adipor1-/- animals. Fat taste loss found in Adipor1-/- males was restored after fat exposure and showed no significant differences in taste behavioral responses to fatty acids with WT controls in two-bottle preference and conditioned taste aversion tests. Adipor1-/- females were found to have diminished preference for LA in two-bottle preference tests, lower intralipid/water lick ratio in a brief-access assay, and reduced avoidance for LA in conditioned taste aversion assay. Furthermore, the taste nerve responses to intralipid and the dietary fat intakes appeared to be the same between Adipor1-/- and WT mice. In the high-fat diet feeding study, Adipor1-/- females gained more weight, while no differences in body weight gain were found in males. Together, we show that adiponectin/AdipoR1 signaling plays crucial sex-specific roles in the modulation of fat taste and the maintenance of healthy body weight primarily by regulating energy expenditure rather than dietary fat intake in mice.

neuroscience↗

bioRxiv2024

Adiponectin signaling modulates fat taste responsiveness in mice

We previously reported that the adiponectin receptor agonist AdipoRon selectively enhances cellular responses to fatty acids in a human taste cell line. The enhancement role of AdipoRon on fatty acid-induced cell responses is mediated by the activation of AMPK and translocation of CD36 on human taste cells. It has also been shown that adiponectin selectively increases taste behavioral responses to intralipid in mice. However, the molecular mechanism underlying the physiological effects of adiponectin on fat taste in mice remains unclear. Here we define AdipoR1 as the mediator responsible for the enhancement role of adiponectin/AdipoRon on fatty acid-induced responses in mouse taste bud cells. Calcium imaging data demonstrate that AdipoRon enhances linoleic acid-induced calcium responses in a dose-dependent fashion in mouse taste cells isolated from circumvallate and fungiform papillae. Similar to the human taste cells, the enhancement role of AdipoRon on fatty acid-induced responses was impaired by the co-administration of an AMPK inhibitor (Compound C) or a CD36 inhibitor (SSO). Utilizing Adipor1-deficient animals we determined the enhancement role of AdipoRon/adiponectin is dependent on AdipoR1 since AdipoRon/adiponectin failed to increase fatty acid-induced calcium responses in taste bud cells isolated from these mice. Brief-access taste tests were performed to determine whether AdipoRons enhancement role was correlated with any differences in taste behavioral responses to fat. Although AdipoRon enhances the cellular responses of taste bud cells to fatty acids, it does not appear to alter fat taste behavior in mice. However, fat naive Adipor1-/- animals were indifferent to increasing concentrations of intralipid, suggesting that adiponectin signaling may have profound effects on the ability of mice to detect fatty acids in the absence of previous exposure to fatty acids and fat-containing diets.

neuroscience↗