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Lower Perception of Odors Intensity in Late Evening May Contribute to Poor Diet Intake in Evening Sleep Phenotypes
Surabhi Bhutani, Paige Sullivan, Victoria Esparza, Kyra Jensen, Matthew Woods, Katie Quis, Uduak George
San Diego State Unversity, San Diego, CA, United States
Evening chronotype (EC), characterized by preference for late bedtime and activity, is linked to unhealthy diet patterns and reduced satiety after 20:00h (biological sleep time), thereby increasing the risk of obesity. Odors guide food choices and exhibit circadian rhythm, yet the relationship between diurnal pattern of smell perception and diet intake in EC remains unclear.Using ecological monetary assessment, healthy-weight participants in Morning chronotype (MC, n=22) and EC (n=21) recorded smell ratings (food and non-food at low and high intensity) and food cravings for 3-days, at 8:00am, 12:00pm, 3:00pm, 6:00pm, 8:00pm, and 10:00pm. The smell identification and threshold scores did not differ between the two chronotypes. Mean intensity ratings for all odors combined were lower for EC vs MC (55.5 vs 42.9, p=0.03). Unlike MC, EC reported food odors to be less intense at 6:00 pm, 8:00 pm, and 10:00 pm (p<0.05). Odor intensity was a significant predictor of fruit craving (β = 0.290, p = 0.033), % calories from carbohydrate (β = -0.442, p = 0.001) and % calories from total sugar (β = -0.253, p = 0.011). Odor intensity was associated with decreases in fruit craving (β = -0.431, p = 0.003) for the EC. The percent of total calories eaten between timepoints decreased in MC, while it remained relatively stable throughout the day in EC (β = 2.307, p = 0.004). No significant difference in appetite ratings were observed by chronotype and time. Our findings indicate that diurnal variation in smell perception is influenced by sleep phenotype, food odors perceived as less
intense toward the end of the day in EC. This observed pattern in smell perception may contribute to intake of unhealthy diet, potentially increasing the risk of obesity and metabolic disorders in EC.
Engineering Insect Olfactory Receptors to Detect Disease Associated Chemicals
Rhodry J. Brown1, Gyu Rie Lee2, Hiroaki Matsunami1
1Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, United States
2Department of Biochemistry, University of Washington, Seattle, WA, United States
Odorant receptors (ORs) are highly sensitive chemical receptors that respond to a diverse range of volatile compounds. While organisms relying on olfaction for survival possess remarkable abilities to detect trace chemicals, our current chemical sensing technology is inadequate in comparison. Recent studies have shown significant differences in the chemical profile of human breath between healthy individuals and those infected with pathogens such as malaria, tuberculosis, or COVID-19. Leveraging the unique chemical profiles associated with diseases could provide a robust method for disease detection. In this study, our objective is to engineer insect ORs to selectively activate in the presence of volatiles associated with diseases. Specifically, we focused on MhOR5, an odorant receptor from the Jumping Bristletail (Machilis hrabei), a basal insect that lacks the OR co-receptor (Orco) found in modern insects. MhOR5 is a well-characterized receptor with broad selectivity and an experimentally determined structure, making it an ideal candidate for targeted engineering. We expressed MhOR5 in a heterologous cell system using HEK293T cells and tested its response to disease-associated volatiles (DAVs). Through structural analysis, we identified key residues that potentially contribute to ligand selectivity, and tested mutations made at these residues for altered ligand selectivity. Our findings revealed distinct ligand selectivity among most mutants in response to individual DAVs. Additionally, we are developing a platform for high-throughput, non-biased screening of combinatorial mutants. This methodology will establish a solid foundation for engineering ORs with specificity towards particular chemicals and for developing engineered OR arrays for disease diagnosis.
Impaired iron gluconate identification in SARS-CoV-2 IgG+ subjects and associated lower transcript levels of the human foliate papillae tongue transcriptome
Barbara Danzer1,2, Mateo Jukic3, Andreas Dunkel2, Gaby Andersen2, Barbara Lieder4,5, Erika Schaudy6, Sarah Stadlmayr4, Jory Lietard6, Timm Michel12, Dietmar Krautwurst2, Bernhard Haller7, Percy Knolle8, Mark Somoza2,6,9, Paul Lingor3,10,11, Veronika Somoza2,4,12
1Technical University of Munich, School of Life Science, Freising, Germany
2Leibniz Institute for Food Systems Biology at the Technical University of Munich, Freising, Germany
3Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, School of Medicine and Health, Munich, Germany
4Department of Physiological Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria
5Current address: Institute of Clinical Nutrition, University of Hohenheim, Stuttgart, Germany
6Department of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria
7Institute of AI and Informatics in Medicine, School of Medicine and Health, Technical University of Munich, Munich, Germany
8Institute of Molecular Immunology, School of Medicine and Health, Technical University of Munich, Munich, Germany
9Chair of Food Chemistry and Molecular Sensory Science, School of Life Sciences, Technical University of Munich, Freising, Germany
10German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
11Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
12Chair of Nutritional Systems Biology, School of Life Sciences, Technical University of Munich, Freising, Germany
Chemosensory impairment reduces the quality of life during and often long after SARS‑CoV‑2 infections. This study investigated the link between sensory impairments due to a former SARS‑CoV‑2 infection, based on correlating changes of the tongue transcriptome. 158 hospital employees were divided into four groups of participants based on previously assessed SARS‑CoV‑2 immunoglobulin G status (IgG±) and self-reported sensory impairment (SSI±). Forced choice taste tests were performed by a subgroup of 141 participants. A whole transcriptome analysis of the foliate papillae area on the tongue was agreed upon by 43 subjects. IgG+ participants choosing the iron gluconate solution correctly had a lower IgG titer than IgG+ subjects who did not identify metallic taste (p = 0.03). Transcriptome analysis of the foliate papillae area isolated from IgG+/SSI+ subjects revealed lower RNA expression levels of 5356 genes in contrast to the other three comparator groups. Investigation of these genes using gene ontology enrichment provided evidence for smell perception as the most impaired biological process. Overall, 166 olfactory receptors (OR) and 9 taste-associated receptors (TAS) had lower transcript levels in IgG+/SSI+ participants. TAS2R7, OR5K1, OR1A2, OR2J2, OR1A1, and OR1G1 are known for an agonist profile, which can be associated with metal perception. In conclusion, odorant receptors on the tongue can be hypothesized to play a role in virus-induced sensory disturbances and metal perception.
Fragrances can affect expression of genes by altering epigenetics
Anandasankar Ray, Rogelio Nunez-Flores, Sachiko Haga-Yamanaka
MCSB, University of California, Riverside, CA, USA
Eukaryotes coevolve with microbiomes and respond to their secreted metabolites. However, little is known about responses to volatile chemicals emitted by microbes. We show that a microbial volatile, diacetyl, and other common related odorants, can alter gene expression in eukaryotes at a distance from their emission source. These structurally-related volatiles inhibit histone-deacetylases (HDACs) differentially. The inhibition occurred with purified human HDACs, increased histone-H3K9 acetylation in human cells, and caused wide changes in gene expression in a range of organisms, including plants, insects, and vertebrates. These epigenetic changes are accompanied by physiological changes in animals and plants. Exposure to vapors slows progression of neurodegeneration in a Drosophila model for Huntington's disease, and neurblastoma cancer cell line, like known HDAC-inhibitor drugs. In plants, different HDAC-inhibitory volatiles alter development programs in roots and shoots. Our findings reveal a highly-conserved atypical signaling pathway that modulates gene expression via changes in chromatin from a chemical source at a distance.
Digital Accessible Remote Olfactory Mediated Health Assessments for Preclinical AD
Andreas Runde1, Colin Magdamo1, Alysa Alejandro Soto1, Benoit Jobin1,2, Alefiya Albers1, Mark Albers1
1Massachusetts General Hospital, Boston, MA, USA, 2Université du Québec à Trois-Rivières, Trois-Rivières, QC, Canada
Early detection of Alzheimer's Disease (AD) is critical to investigate the efficacy of therapies prior to the onset of symptoms. Many studies have demonstrated that olfactory dysfunction is a biomarker that predicts cognitive decline in presymptomatic stages of AD. We developed the remote AROMHA Brain Health Smell Test (consisting of odor percept identification (OPID), percepts of odor episodic memory (POEM), and odor discrimination (OD)) to assess olfactory function and validated self-administration in at-home settings. Participants determined to be cognitively normal (CN) via self-report or cognitive assessment from the Massachusetts Alzheimer's Disease Research Center (MADRC) were given the option to self-administer the smell test. 66 CN participants (mean age: 41.8) were observed during self-administration (in-person or via Zoom), while 29 (mean age: 63.0) opted for self-administration without observation. These two groups performed similarly across OPID (p=0.59), identification confidence (p=0.22), OD (p=0.68), POEM (p=0.436), and odor intensity (p=0.77). Through the MADRC, we recruited 28 subjects who expressed Subjective Cognitive Complaints (SCC) or received a Mild Cognitive Impairment (MCI) diagnosis. They performed significantly worse than CN participants in unadjusted analyses on OPID (p<0.001), OD (p=0.0013), and POEM (p=0.0041), while having lower odor intensity (p=0.016), and identification confidence (p<0.001). The AROMHA Brain Health Test's accessibility through self-administration makes it suitable for widespread use. As a non-invasive, time-efficient screening tool, the test holds promise for early AD detection. Incorporation in clinical trials and epidemiological studies with key biomarkers for detection of AD and other related dementias is ongoing to provide further validation.
Enhancing Preclinical Alzheimer Cognitive Composite (PACC) via Olfactory Testing
Qing X Yang, Prasanna Karunanayaka, , Biyar Ahmed, Rommy Elyan, Ren Pang
Penn State College of Medicine, Hershey, PA, USA
The ultimate goal of Alzheimer disease (AD) research is to develop methods for prevention and treatment AD from "presymptomatic" phases of the disease. It is important to first develop outcome measures sensitive to the earliest disease-related changes. Recent years, a cognitive composite outcome measure of Preclinical Alzheimer Cognitive Composite (PACC) has been developed, for clinical trial in preclinical AD. The PACC combines tests that assess episodic memory, timed executive function, and global cognition. It has long been established that olfactory deficits are prevalent in early MCI and AD which can precede symptoms of memory and cognitive decline. Longitudinal studies of patients have indicated that olfactory deficits are related to the severity of dementia and are significantly different from normal aging effects. Thus, the objective of this report is to examine if odor identification and threshold can be used for assessing AD severity above and beyond cognitive impartments included in the PACC. In this study, MCI (n=20, 11 F, age 70.10 ± 7.48) and healthy controls (HC) (n=27, 18 F, age 65.15 ± 5.44) underwent neuropsychological testing and olfactory identification and threshold testing. Principal component analysis was performed with the neuropsychological test scores followed by a linear model regression correlating the category the participant was placed in, i.e., HC or MCI, versus the principal components and age with and without olfactory measures. A two-way ANOVA test resulted in a Chi-squared value of 0.0277. These findings demonstrated that olfactory testing scores improves the ability to distinguish MCI from HC.
Determinants of Sweet Taste Liking in Individuals of African and East Asian Ancestry Groups Living in the United States
Lauren Zami1, Fabien Ca1, Faye Guarneri1, Liz Cortes1, Janel Clovis1, Caren Ghali1,2, May M Cheung1
1City University of New York, Brooklyn College, Brooklyn, NY, USA, 2City University of New York, Macaulay Honors College, New York, NY, USA
Some people like sweet taste more than others. Individual differences in sweet taste liking may be influenced by environmental exposure to sweet taste (i.e., habitual added sugars intake during early childhood), and these factors may differ across ancestry groups. Theoretically, migrants born in countries with a lower overall added sugars intake than the U.S. may be exposed to less sweet-tasting foods during early life. To identify the determinants of sweet liking, we collected data on sweet taste liking, anthropometric measurements, demographics data, and dietary intake from 121 young adults (age 22.2 ± 5.9 years) from two underrepresented groups in research in the U.S., the African and East Asian ancestry groups, with 51 (19 African and 32 East Asian) migrants. Sweet taste liking data was collected at home using the Simple Sweet Test, a psychophysical method. Participants were further categorized into sweet Dislikers, Moderate Likers, and Extreme Likers. Added sugars intake was assessed using the Short Healthy Eating Index Survey, a validated food frequency questionnaire. We found that a higher percentage of U.S.-born individuals are Moderate Likers and Extreme Likers in both ancestry groups. Sweet taste liking was positively associated with added sugars intake only among migrants but not U.S.-born individuals. This suggests that the high-sweet food environment in the U.S. may favor the development of sweet-liking tendencies. Furthermore, the discordance between sweet liking and added sugars intake in U.S.-born individuals may indicate aberrant taste and food relationships. Future studies should aim to understand how individual genetics and cultural background contribute to a person's unique taste preferences.
