Peripheral taste receptor cells use multiple signaling pathways to transduce taste stimuli into output signals that are sent to the brain. Transient receptor potential melastatin 5 (TRPM5), a sodium-selective TRP channel, functions as a common downstream component in sweet, bitter, and umami signaling pathways. In the absence of TRPM5, mice have a reduced, but not abolished, ability to detect stimuli, suggesting that a TRPM5-independent pathway also contributes to these signals. Here, we identify a critical role for the sodium-selective TRP channel TRPM4 in taste transduction. Using live cell imaging and behavioral studies in KO mice, we show that TRPM4 and TRPM5 are both involved in taste-evoked signaling. Loss of either channel significantly impairs taste, and loss of both channels completely abolishes the ability to detect bitter, sweet, or umami stimuli. Thus, both TRPM4 and TRPM5 are required for transduction of taste stimuli.
Taste receptor cells use multiple signaling pathways to detect chemicals in potential food items. These cells are functionally grouped into different types: Type I cells act as support cells and have glial-like properties; Type II cells detect bitter, sweet, and umami taste stimuli; and Type III cells detect sour and salty stimuli. We have identified a new population of taste cells that are broadly tuned to multiple taste stimuli including bitter, sweet, sour, and umami. The goal of this study was to characterize these broadly responsive (BR) taste cells. We used an IP 3 R3-KO mouse (does not release calcium (Ca 2+) from internal stores in Type II cells when stimulated with bitter, sweet, or umami stimuli) to characterize the BR cells without any potentially confounding input from Type II cells. Using live cell Ca 2+ imaging in isolated taste cells from the IP 3 R3-KO mouse, we found that BR cells are a subset of Type III cells that respond to sour stimuli but also use a PLCβ signaling pathway to respond to bitter, sweet, and umami stimuli. Unlike Type II cells, individual BR cells are broadly tuned and respond to multiple stimuli across different taste modalities. Live cell imaging in a PLCβ3-KO mouse confirmed that BR cells use this signaling pathway to respond to bitter, sweet, and umami stimuli. Short term behavioral assays revealed that BR cells make significant contributions to taste driven behaviors and found that loss of either PLCβ3 in BR cells or IP 3 R3 in Type II cells caused similar behavioral deficits to bitter, sweet, and umami stimuli. Analysis of c-Fos activity in the nucleus of the solitary tract (NTS) also demonstrated that functional Type II and BR cells are required for normal stimulus induced expression.
Original Article OBESITY BIOLOGY AND INTEGRATED PHYSIOLOGY Study ImportanceWhat is already known?► Obesity is often associated with impaired taste. ► The mechanisms associating obesity and taste are poorly understood. What does this study add?► Our study on diet-induced obese mice demonstrates that high-fat diet and excess weight can each contribute to impaired taste. ► There is selectivity in the effects of diet and weight that varies by stimulus.Objective: Previous studies have reported that individuals with obesity have reduced taste perception, but the relationship between obesity and taste is poorly understood. Earlier work has demonstrated that diet-induced obesity directly impairs taste. Currently, it is not clear whether these changes to taste are due to obesity or to the high-fat diet exposure. The goal of the current study was to determine whether diet or excess weight is responsible for the taste deficits induced by diet-induced obesity.Methods: C57BL/6 mice were placed on either high-fat or standard chow in the presence or absence of captopril. Mice on captopril did not gain weight when exposed to a high-fat diet. Changes in the responses to different taste stimuli were evaluated using live cell imaging, briefaccess licking, immunohistochemistry, and real-time polymerase chain reaction.Results: Diet and weight gain each affected taste responses, but their effects varied by stimulus. Two key signaling proteins, α-gustducin and phospholipase Cβ2, were significantly reduced in the mice on the highfat diet with and without weight gain, identifying a potential mechanism for the reduced taste responsiveness to some stimuli. Conclusions: Our data indicate that, for some stimuli, diet alone can cause taste deficits, even without the onset of obesity.Obesity (2020) 28, 284-292.
WT1 is a transcriptional activator that controls the boundary between multipotency and differentiation. The transcriptional cofactor BASP1 binds to WT1, forming a transcriptional repressor complex that drives differentiation in cultured cells; however, this proposed mechanism has not been demonstrated in vivo. We used the peripheral taste system as a model to determine how BASP1 regulates the function of WT1. During development, WT1 is highly expressed in the developing taste cells while BASP1 is absent. By the end of development, BASP1 and WT1 are co-expressed in taste cells, where they both occupy the promoter of WT1 target genes. Using a conditional BASP1 mouse, we demonstrate that BASP1 is critical to maintain the differentiated state of adult taste cells and that loss of BASP1 expression significantly alters the composition and function of these cells. This includes the de-repression of WT1-dependent target genes from the Wnt and Shh pathways that are normally only transcriptionally activated by WT1 in the undifferentiated taste cells. Our results uncover a central role for the WT1–BASP1 complex in maintaining cell differentiation in vivo.
Objective Previous studies have reported that individuals with obesity have reduced taste perception, but the relationship between obesity and taste is poorly understood. Earlier work has demonstrated that diet‐induced obesity directly impairs taste. Currently, it is not clear whether these changes to taste are due to obesity or to the high‐fat diet exposure. The goal of the current study was to determine whether diet or excess weight is responsible for the taste deficits induced by diet‐induced obesity. Methods C57BL/6 mice were placed on either high‐fat or standard chow in the presence or absence of captopril. Mice on captopril did not gain weight when exposed to a high‐fat diet. Changes in the responses to different taste stimuli were evaluated using live cell imaging, brief‐access licking, immunohistochemistry, and real‐time polymerase chain reaction. Results Diet and weight gain each affected taste responses, but their effects varied by stimulus. Two key signaling proteins, α‐gustducin and phospholipase Cβ2, were significantly reduced in the mice on the high‐fat diet with and without weight gain, identifying a potential mechanism for the reduced taste responsiveness to some stimuli. Conclusions Our data indicate that, for some stimuli, diet alone can cause taste deficits, even without the onset of obesity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.