A subset of broadly responsive Type III taste cells contribute to the detection of bitter, sweet and umami 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 IP3R3-KO mouse (does not release calcium (Ca2+) 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 Ca2+ imaging in isolated taste cells from the IP3R3-KO mouse, we found that BR cells are a subset of Type III cells that respond to sour stimuli but also use a PLCß 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 PLCß3-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 PLCß3 in BR cells or IP3R3 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.

Comparison of transvalvular flow rate in aortic stenosis subtypes.

OBJECTIVES: Evaluate ET and TVFR in normal patients, PLFLGAS, LGLFAS, and classic pre and post TAVR. BACKGROUND: Severe aortic stenosis (AS) is defined echocardiographically. Generating a pressure gradient to meet diagnostic criteria is dependent on left ventricular contractility, stroke volume, and ejection time.  Abnormalities in these decrease the mean pressure gradient across the valve creating pathology termed low flow, low gradient AS. This occurs in two subtypes, low ejection fraction LFLGAS and paradoxical LFLGAS (PLFLGAS), in which EF is normal but stroke volume is < 35 ml/m2 . Paradoxical LFLGAS is difficult to diagnose and does not have a confirmatory echocardiographic parameter. Transvalvular flow rate (TVFR), which is defined as stroke volume divided by the ejection time, provides a direct measure of flow across the aortic valve. METHODS: A retrospective study of patients who underwent transcatheter aortic valve replacement (TAVR) at the University of Cincinnati Medical Center between 2016 and 2019 was performed. Patients were classified by AS subtype. ET and TVFR were measured pre and post TAVR and statistically compared using SPSS statistics software and ANOVA analysis. RESULTS: Pre TAVR TVFR in the normal population, severe AS population, and LFLGAS were not significantly different. The pre TAVR TVFR in paradoxical LFLGAS patients was significantly lower than other groups. TVFR improved to the greatest degree post TAVR in PLFLGAS but did not meet statistical significance. CONCLUSIONS: The significantly lower TVFR demonstrated in PLFLGAS provides a comprehensive, direct measurement of aortic valve hemodynamics and PLFLGAS pathology and can aid in diagnosis.

Differential Effects of Diet and Weight on Taste Responses in Diet-Induced Obese Mice.

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 Cß2, 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.