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Fat Hedonic Ratings as a Function of Obesity in Humans
Nicholas Amado1, Judith Storch1, Paul Breslin1,2
1Rutgers University, New Brunswick, NJ, United States, 2Monell Chemical Senses Center, Pittsburgh, PA, United States

Obesity has been correlated with decreased fatty acid taste sensitivity and increased fat intake in humans, leading to greater consumption of calorically dense foods, perpetuating weight gain. Importantly, high fat, high carbohydrate foods are obesogenic and taste changes with obesity might influence further intake of obesogenic foods. We tested the hypothesis that obese humans have a higher preference for a high fat, highly palatable food relative to lean humans. 5 high BMI (≥ 30 kg/m2) and 8 low BMI (≤ 25 kg/m2) subjects were given 5 frostings (Crisco, sucrose syrup, vanilla extract) of varying fat:sugar ratios (1:3, 2:3, 1:1, 4:3, 5:3) and asked to rate liking of each frosting on a bidirectional labeled hedonic scale in duplicate. Our results showed that high BMI participants rated all frosting ratios positively (above 0) on a labeled hedonic scale, whereas low BMI participants rated the fattier ratios (4:3 and 5:3) negatively (below 0). Overall, high BMI participants had an average hedonic liking rating of 11.5 (slight to moderate liking) versus a 5.5 (neutral to slight liking) for the low BMI participants averaged across all 5 ratios (p<0.01). These results suggest that the physiology of obesity influences fat liking. This observation has important implications for the overconsumption of high fat: high carbohydrate, highly palatable food in our society. If eating these foods increases perceived palatability of these foods, then a positive feedback loop could induce spiraling weight gain. Future work will consist of replicating this experiment in mice and measuring fatty acid detection thresholds in humans to understand if fat liking is positively correlated with fat taste insensitivity. Understanding how obesity affects taste function will help guide us to better therapies for obesity.

Individual Differences in the Taste of Excipients and an Over-the-Counter Pediatric Medicine
Julie A. Mennella1, Mengyuan Kan2, Elizabeth D. Lowenthal3, Joel Mainland1, Blanca E. Himes2, M. Yanina Pepino4
1Monell Chemical Senses Center, Philadelphia, PA, United States, 2University of Pennsylvania, Department of Biostatistics, Epidemiology and Informatics, Philadelphia, PA, United States, 3University of Pennsylvania Perelman School of Medicine, Department of Pediatrics, Philadelphia, PA, United States, 4University of Illinois at Urbana-Champaign, Urbana, IL, United States

Objective. Our research program aims to systematically determine the sources of variation in the flavor of pediatric medicines and their excipients. The present study focused on a popular, over-the-counter, non-steroidal anti-inflammatory medicine (Berry-flavored Children’s Motrin™ Oral Suspension) of which ibuprofen is the active pharmaceutical ingredient and Acesulfame K (Ace K) and sucrose are sweetening excipients. Methods. Trained adult panelists (n = 154) used the general Labelled Magnitude Scale (gLMS) and hedonic gLMS after tasting 5mL of 0.012M Ace K and 0.6M sucrose and after swallowing 5mL of Motrin. Genotypes for 141 panelists were obtained by using Illumina Infinium Global Screening Array v3.0 Beachip, and association analyses with sensory phenotypes were conducted on several candidate single nucleotide polymorphisms (SNPs) near or within genes that encode selected taste receptors. Results. Hedonic ratings for Motrin ranged from -64 (strong dislike) to 98 (strongest imaginable like). Consistent with prior findings, SNP rs3741845 within the TAS2R9 bitter receptor gene was associated with the bitterness of Ace K (p <0.001). While SNP rs35744813 within the TAS1R3 sweet receptor gene was associated with the sweetness of Motrin (p = 0.01), the association with the sweetness of sucrose did not reach significance (p = 0.07). Overall, hedonic ratings of Motrin were positively related to hedonic ratings of both sweetening excipients (correlation efficient > 0.3; p <0.001). Conclusions. Investigations into the taste of excipients provided insights into sources of individual difference in the palatability of the complex flavor of a pediatric medicine. Distinct variations in how a given medicine tastes and whether a child is willing to ingest it support a precision medicine approach.

Are you healthy or sick? Conspecific sickness-related cue recognition in mice
Friederike D. Seifert1, Marco Niestroj1, Maciej Winiarski2, Anna Bryska2, Lydia Kopplin3, Ana M. Izcue3, Janardhan Bhattarai5, Yingqi Wang5, Alicja Puścian2, Minghong Ma5, Pavel Stopka4, Oliver Pabst3, Ewelina Knapska2, Marc Spehr1
1RWTH Aachen University, Institute for Biology II / Dept. Chemosensation, Aachen, Germany 2Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland 3RWTH Aachen University, Institute of Molecular Medicine, Aachen, Germany 4Biotechnology and Biomedicine Center of the Academy of Sciences and Charles University in Vestec, Prague, Czech Republic 5University of Pennsylvania, Department of Neuroscience, Philadelphia, PA, United States

Chemosensory assessment of a conspecific's health status is essential for rodent social behavior. We hypothesize that health status detection during social interactions is mediated via the accessory olfactory system. We address this issue using an integrated approach. Combining chemical analysis of rodent secretions, physiological analysis of vomeronasal sensory neuron activity in response to chemosignals from healthy versus sick individuals, and behavioral responses to such stimuli, we aim to uncover neuronal mechanisms underlying detection of sickness-related chemosignals. Using RAG-KO mice, which develop colitis upon T-cell injection, we collect bodily secretions (urine and bedding) of sick individuals at various stages of disease progression. Using these stimuli, we test for activation of the accessory olfactory system. Our results reveal i) the molecular identity of candidate sickness-related cues, and ii) health state-dependent activation patterns in sensory neurons within the vomeronasal organ. Employing genetically labeled sensory neurons that express a defined vomeronasal receptor, we investigate a potential role of this receptor in disease-specific cue detection. Finally, we report behavioral data that support the notion of sickness-related cue processing via the accessory olfactory system.

Longitudinal At Home Smell Testing to Detect and Follow Infection by SARS-CoV2
Daniela Delphus1, Colin Magdamo1, Alysa Alejandro Soto1, Arthur Kim1, Alefiya Albers2, Mark Albers1
1Dept. of Neurology, Massachusetts General Hospital, Boston, MA, United States, 2Dept. of Psychology, Endicott College, Beverly, MA, United States

Between 30 -80% of patients with COVID-19 self-report a loss of smell function. However, self-reported anosmia and hyposmia have not been accurate indicators of objective smell function. Furthermore, up to a third of people with COVID-19 suffer prolonged symptoms, including smell loss or distortions of smell (parosmia), for months or years, which has been termed post-acute sequalae of SARS-CoV-2 infection (PASC). To evaluate hypotheses about what predicts smell loss due to incident COVID-19 infection and what drives recovery rates for olfactory dysfunction following COVID-19 infection, we developed the Aromha COVID Smell Test, an at-home longitudinal test comprised of physical cards that gauge distinct components of objective smell function (intensity percepts, identification, discrimination) and a web app to collect responses. We will collect data on other covariates involved in the recovery of smell function, such as age, race, ethnicity, education, sex, vaccination status, severity of initial smell loss, and socioeconomic status. We will use a mixed effects longitudinal model to predict trajectories of recovery of smell function in individuals with COVID-19 over time. We have collected our data from both English and Spanish-speaking populations. We will present analyses of our longitudinal objective smell test to quantify smell loss caused by new SARS-CoV2 infections and to quantify the rates of recovery in olfaction amongst individuals who have had a past COVID infection. Our results may help to inform power calculation for therapeutic trials of investigational and repurposed drugs to accelerate or enhance recovery of COVID-19 related smell dysfunction.

Sorting of Odor Dilutions Is a Meaningful Addition to Assessments of Olfactory Function
Thomas Hummel1, Anne Huster1, Jörn Lötsch2,3
1Smell & Taste Clinic, Department of Otorhinolaryngology, TU Dresden, Dresden, Germany, 2Institute of Clinical Pharmacology, Goethe-University, Frankfurt a.M., Germany, 3Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt a.M., Germany

Background: The categorization of individuals as normosmic, hyposmic, or anosmic from test results of odor threshold, discrimination, and identification may provide a limited view of the sense of smell. The purpose of this study was to expand the clinical diagnostic repertoire by including additional tests. Methods: A random cohort of n = 135 individuals (83 women and 52 men, aged 21 to 94 years) was tested for odor threshold, discrimination, and identification, plus a distance test, in which the odor of peanut butter is perceived, a sorting task of odor dilutions for phenylethyl alcohol and eugenol, a discrimination test for odorant enantiomers, a lateralization test with eucalyptol, a threshold assessment after 10 min of exposure to phenylethyl alcohol, and a questionnaire on the importance of olfaction. Unsupervised methods were used to detect structure in the olfaction-related data, followed by supervised feature selection methods from statistics and machine learning to identify relevant variables. Results: The structure in the olfaction-related data divided the cohort into two distinct clusters with n = 80 and 55 subjects. Odor threshold, discrimination, and identification did not play a relevant role for cluster assignment, which, on the other hand, depended on performance in the two odor dilution sorting tasks, from which cluster assignment was possible with a median 100-fold cross-validated balanced accuracy of 77–88%. Conclusions: The addition of an odor sorting task with the two proposed odor dilutions to the odor test battery expands the phenotype of olfaction and fits seamlessly into the sensory focus of standard test batteries.

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