ORAL METABOLIC SENSING OF SUGARS BY HUMANS

• Sponsoring Institution: National Institute of Food and Agriculture
• Project Status: COMPLETE
• Funding Source: HATCH
• Reporting Frequency: Annual
• Accession No.: 1009778
• Project Start Date: Jun 20, 2016
• Project End Date: May 14, 2021
• Program Code: [(N/A)]- (N/A)

Recipient Organization
RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY
3 RUTGERS PLZA
NEW BRUNSWICK,NJ 08901-8559

Performing Department
Nutritional Sciences

Non Technical Summary
According to the Centers for Disease Control and Prevention (CDC), 36% of American adults are obese and 17% are overweight. Furthermore, the CDC reports that from 1990 to 2010 obesity increased dramatically among US adults. Along with the increasing girth there has been an increase in obesity-related diseases: diabetes, metabolic syndrome, and heart disease. Although the proximate cause(s) for the increased incidence of obesity during the past few decades is unknown, arguments have been made for overconsumption of calorie-rich foods and/or of starch and sugar-sweetened insulinogenic beverages, decreased physical activity, and decreased breast-feeding. Regardless of which factors contribute most to obesity, an energy imbalance with higher consumption vs. expenditure of calories is key, and the stimulation of insulin is necessary. Preferential consumption of sugary sodas and fruit juices over lower-calorie beverages and potential differences in satiation from calories in liquid vs. solid form are known contributors. Replacing sugars in beverages with non-caloric sweeteners or otherwise diminishing consumption of sugar-rich beverages may aid weight loss or dampen weight gain. Diet sodas, however, are often not as effective as water consumption at reducing weight, and consumers overwhelmingly prefer caloried sodas to no-calorie sodas.The functional imaging studies and psychophysical taste experiments proposed in this research will determine if sugar transporters and metabolic sensors are present and active in human taste cells and if they are likely to contribute to sugar perception in humans. Improving our understanding of the roles of glucose signaling in taste may help prevent and control obesity, diabetes, and metabolic syndrome, which now afflict greater than 25% of Americans. This is a NIFA priority area as it affects Childhood Obesity and associated diseases in children.

Animal Health Component

0%

Research Effort Categories

Basic

100%

Applied

0%

Developmental

0%

Classification

Knowledge Area (KA)	Subject of Investigation (SOI)	Field of Science (FOS)	Percent
701	7010	1020	100%

Knowledge Area
701 - Nutrient Composition of Food;

Subject Of Investigation
7010 - Biological Cell Systems;

Field Of Science
1020 - Physiology;

Keywords

sugar

diabetes

energy sensing

metabolic cues

taste

Goals / Objectives
We hypothesize that entry of glucose along with Na+ via SGLT1 leads to depolarization of sweet-responsive TAS1R2+/TAS1R3+ taste cells in humans as it does in rodents. We hypothesize further that metabolism of glucose transported into TAS1R2+/TAS1R3+ taste cells by GLUTs and/or SGLTs, leads to elevated intracellular ATP that closes the sweet taste cell KATP channel, depolarizing the cell. The main goals of this project are to provide initial tests of these hypotheses by anatomical and functional studies with human taste cells and psychophysical taste tests of human subjects. Immuno-histochemical and PCR-based techniques will determine if GLUTs, SGLTs, and KATP channel subunits previously found in mouse taste cells are present also in human taste cells. Functional studies in human taste cells will probe the involvement of KATP in responses to sugars. Psychophysical experiments will be carried out with human subjects exposed to sugars with or without pharmacologically active modifiers of KATP. Together these studies will determine if sugar transporters and KATP channels are present in human taste cells and if they likely contribute to sugar perception in humans.

Project Methods
There is strong evidence that the sweet taste receptor subunits T1R2 and T1R3, encoded by TAS1R2 and TAS1R3, are key to the sense of sweet taste in humans. Despite the clear importance of T1R receptors to sweet taste, there is also evidence from human and animal studies that alternative pathways exist for detection and/or modulation of sweet taste. Commonalities among taste cells of the tongue and taste-like cells of the gut and pancreas make it plausible that "intestinal-type" sugar transporters (e.g., glucose transporters (GLUTs) and sodium-glucose co-transporters (SGLTs)) and "pancreatic-type" metabolic sensors (ATP-gated KATP channels) might also be present in human taste cells to contribute to the sensation of sugar's sweetness. The main goal of this project is to identify and characterize T1R-independent mechanisms used by human taste receptor cells to sense sugars.We hypothesize that sugar transporters and metabolic sensors are present in sweet-responsive TAS1R2- and TAS1R3-positive (TAS1R2+/TAS1R3+) human taste receptor cells, where they constitute a sugar-sensing pathway independent of T1Rs. We also hypothesize that metabolic responses of human taste cells contribute to the transduction and/or perception of sweet taste and impart a stronger preference for nutritive over non-caloric sweeteners. We hypothesize further that metabolism of glucose transported into sweet-responsive TAS1R2+/TAS1R3+ human taste receptor cells leads to elevated intracellular ATP that closes the taste cell's KATP channels, causing depolarization. We will test these hypotheses using histological and functional studies in human taste tissues and cells (A.1) and psychophysical taste tests in human subjects (A.2). Immuno-histochemical and nucleic-acid-based techniques will determine if GLUTs, SGLTs, and KATP channel subunits previously found in Tas1r3+ mouse taste cells are also present in human TAS1R2+/TAS1R3+ taste cells. Functional imaging will determine their role in human taste receptor cell responses to sugars. Psychophysical taste experiments with human subjects exposed to sugars with or without non-caloric pharmacological modifiers of KATP will determine effects on perception, liking, and preference.RNA probes for in situ hybridization are transcribed from verified full-length human cDNA plasmids obtained from Open Biosystems or imaGenes. Probes are first tested in in situ hybridizations with mouse taste tissue (our probes for human genes are preselected such that the nucleotide match to the orthologous mouse gene is >80%). Based on published information about gene expression, probes are also tested with suitable positive control human tissues obtained from Zyagen (e.g., pancreas, liver, intestine, heart, kidney, testes). Primary antibodies for indirect immuno-histochemistry are obtained from commercial sources (e.g., Alpha Diagnostics, Millipore, Abcam). Antibodies also are tested with mouse taste tissue and positive control human tissues from Zyagen. Antibody controls include minus primary and plus cognate blocking peptide. We have shown our ability to use single and double indirect immuno-histochemistry on human taste buds. Cryostats and confocal microscopes are available to us in our laboratory.

Progress 06/20/16 to 05/14/21

Outputs
Target Audience:This project benefits the general population both with the knowledge gained on human carbohydrate phsyiology and metabolism and aditionally has public health implications for how to reduce sugar intake and formulate reduce calorie foods and beverages. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?The project has provided opportunity for research for three graduate students and two undergraduates to learn about how to ask research questions, design research studies, collect data, ananlyze data, determine if the data form an answer to the research question and to report results in verbal and written published forms. How have the results been disseminated to communities of interest?The results have been disseminated by generating articles that have been published in peer-reviewed scientific journals and by giving presentations at local and national conferences. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? Our team was able to successfully identity that humans have glucose metabolic signaling proteins within human taste cells. We also determined that when these cells are cultured in vitro that they respond to glucose in a manner that can be enhanced by K-ATP channel cosing agents and dimished by K-ATP channel opening agents. These same pharamcological agents have parallel effects on human percpetually when rinsed orally and gluccose is deteced. That is, K-ATP channel opening agents that are rinsed orally make people less sensitive to glucose orally, and when K-ATP closing agnets are rinsed orally, subjects become more sensitive to oral glucose. We further showed that the glucose transporter SGLT which is enhanced by the presence of sodium and impeded by pharmacological blockade is involved with human oral glucose detection. Oral sodium enhances human glucose detection and the SGLT blocker impedes human glucose detection. This project is the first to demonstrate that humans can sense glucose in the mouth via metabolic signaling in tate tissue in addition to sweet taste detection. This work has implications for sugar intake reduction and for engineering foods and beverages to be satisfying with fewer sugars.

Publications

• Type: Journal Articles Status: Published Year Published: 2021 Citation: Harmon, C.P., Deng, D., Breslin P.A.S. (2021). Bitter Taste Receptors (T2Rs) are Sentinels that Coordinate Metabolic and Immunological Defense Responses. Current Opinions in Physiology, 20: 70-76. PMID: 33738371
• Type: Journal Articles Status: Published Year Published: 2021 Citation: Hanselman, E.C., Amado, N.J., Breslin, P.A.S. (2021). Oral Signals of Short and Long Chain Fatty Acids: Parallel Taste Pathways to Identify Microbes and Triglycerides. Current Opinions in Physiology, 20: 126-133. PMID: 33738372
• Type: Journal Articles Status: Published Year Published: 2021 Citation: Honarbakhsh, M., Ericsson, A., Zhong, G., Isoherranen, N., Zhu, C., Bromberg, Y., Van Buiten, C., Raskin, I., Malta, K., Joseph, L., Lakey, A., Storch, J., Vetriani, C., Chikindas, M., Breslin, P., Quadro, L. (2021). Subclinical vitamin A deficiency perturbs intestinal barrier functions and fecal microbiome: insights from a tunable mouse model of vitamin A deficiency, Journal of Lipid Research, 13;62:100046. PMID: 33587919
• Type: Journal Articles Status: Published Year Published: 2021 Citation: Schwiebert, E., Wang, Y., Xi, R., Choma, K., Streiff, J., Flammer, L.J., Rivers, N., Ozdener, M.H., Margolskee, R.F., Christensen, C.M., Rawson, N.E., Jiang, P., Breslin, P.A.S. (2021). Inhibition of bitter taste from oral Tenofovir Alafenamide (TAF). Molecular Pharmacology. 99, 319-327. PMID: 33824185
• Type: Journal Articles Status: Published Year Published: 2021 Citation: Breslin, P.A.S., Izumi, A., Tharp, A., Ohkuri, T., Yokoo, Y., Flammer, L.J., Rawson, N.E., Margolskee, R.F. (2021). Evidence that human oral glucose detection involves a sweet taste pathway and a glucose transporter pathway. PLoS One. 16(10):e0256989. PMID: 34614010
• Type: Journal Articles Status: Awaiting Publication Year Published: 2022 Citation: Frank, H.R., Amato, K., Trautwein, M., Maia, P., Liman, E.R., Nichols, L.M., Schwenk, K., Breslin, P.A.S., Dunn, R.R. (2022). Evolution of sour taste. Proceedings of the Royal Society B. (In Press).

Progress 10/01/19 to 09/30/20

Outputs
Target Audience:Target audiences include individuals, groups, market segments, or communities that were served by the project. Also included are population groups such as racial and ethnic minorities and those who are socially, economically, or educationally disadvantaged. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?I have two graduate student who are now interested in oral metabolic sensing of macronutrients. They are dovetailing their interests to this project to study oral metabolic sensing of short and long chain fatty acids and their signaling to the rest of the body both neurally and humorally. How have the results been disseminated to communities of interest?Through peer reviewed publications What do you plan to do during the next reporting period to accomplish the goals?We will be examining the role of oral membrane-bound disaccharide enzymes that generate monosaccharides to stimulate oral metabolic sensing. The studies will parallel the type of work conducted in the past period but will involve disaccharides that have the potential to control the degree to whcih disaccharides stimulate sweet taste and also activate the metabolic signaling pathway that requires monosaccrides to function.

Impacts
What was accomplished under these goals? We determined that in addition to human oral detection of glucose being enhanced by the addition of NaCl (the co-transport molecule with glucose for SGLT) that detection was severely impaired by oral rinsing with phlorizin the SGLT inhibitor. We conducted parallel control experiments with fructose, sucralose, and alpha-methyl-D-glucopyranoside (MDG). Fructose, the mono-saccharide, is not transported by SGLT and detection for it was neither enhanced nor impaired by NaCl and phlorizin. Similar results were obtained for the non-caloric high potency sweetener sucralose. MDG is a glucose analog that can be transported by SGLT but can not be metabolized within the cell to ATP. Thresholds for MDG tended to be enhanced by the presence of NaCl and was significantly impaired by the addition of phlorizin. These data indidate that the glucose metabolic signaling pathway activation in taste cells is not only due to the metabolic generation of ATP acting on KATP channels, but the transport of glucose into the cell by SGLT generates a signal by itself in the absence of ATP generation, most likely due to the movement of sodium ions into the cells during glucose transport.

Publications

• Type: Journal Articles Status: Published Year Published: 2020 Citation: Studies of human twins reveal genetic variation that affects dietary fat perception. Lin C, Colquitt L, Wise P, Breslin PAS, Rawson NE, Genovese F, Maina I, Joseph P, Fomuso L, Slade L, Brooks D, Miclo A, Hayes JE, Sullo A, Reed DR. Chem Senses. 2020 Jun 9;45(6):467-81. doi: 10.1093/chemse/bjaa036

Progress 10/01/18 to 09/30/19

Outputs
Target Audience:Target audiences include individuals, groups, market segments, or communities that were served by the project. Also included are population groups such as racial and ethnic minorities and those who are socially, economically, or educationally disadvantaged. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?I have a graduate student who is now interested in oral metabolic sensing of macronutrients. He is dovetailing his interests to this project to study oral metabolic sensing of fats and their signaling the rest of the body via endocannabinoid release. How have the results been disseminated to communities of interest?Through peer reviewed publications What do you plan to do during the next reporting period to accomplish the goals?We will be examining the role of glucose metabolites to stimulate oral metabolic sensing without actually carrying many calories to the body. The studies will parallel the type of work conducted in the past period but will involve compounds that have the potential to effectively trick the metabolic sensor into signaling calories when there are relatively few present.

Impacts
What was accomplished under these goals? The taste stimulus glucose comprises approximately half of the commercial sugar sweeteners used today, whether in the form of the di-saccharide sucrose (glucose-fructose) or half of high-fructose corn-syrup (HFCS). Glucose has, therefore, been presumed to serve principally as a sweetener in the mouth. In light of recent rodent data on the role of oral metabolic glucose signaling, we examined psychopharmacologically whether oral glucose detection may also involve an additional pathway to the traditional sweet taste transduction pathway of activating the class 1 taste receptors T1R2/T1R3. In three experiments we compared oral glucose detection thresholds to sucralose thresholds without and with addition of: 1) the T1R receptor inhibitor Na-lactisole, 2) the glucose co-transport component sodium (NaCl), and 3) the sodium-glucose co-transporter (SGLT) inhibitor phlorizin. In each experiment, psychopharmacological data were consistent with glucose engaging additional signaling pathways to the sweet taste pathway. Lactisole addition impaired detection of the high potency sweetener (HPS) sucralose much more than it did glucose, consistent with glucose using additional signaling pathways. The addition of NaCl had a beneficial impact on the detection of glucose and impaired sucralose detection, consistent with glucose utilizing a sodium-glucose co-transporter. The addition of the SGLT inhibitor phlorizin impaired detection of glucose more than it did sucralose, consistent with glucose utilizing a sodium-glucose co-transporter. Together, these results support the idea that oral detection of glucose engages two signaling pathways: one that utilizes an SGLT glucose transporter and the other comprised of the T1R2-T1R3 sweet taste receptor.

Publications

• Type: Journal Articles Status: Published Year Published: 2019 Citation: Hwang, L.D., Strike, L.T., Couvy-Duchesne, B., de Zubicaray, G.I., McMahon, K., Breslin, P.A.S., Reed, D.R., Martin, N.G., Wright, M.J. (2019). Associations between brain structure and perceived intensity of sweet and bitter tastes. Behavior Brain Res. 363:103-108. PMID: 30703394
• Type: Journal Articles Status: Published Year Published: 2019 Citation: Wise, P.M, Damani, S., Breslin, P.A.S. (2019). Sodium, but not potassium, blocks bitterness in simple model chicken broths. Journal of Food Science and Technology 56: 3151-3156. PMID: 31205370
• Type: Books Status: Published Year Published: 2019 Citation: Breslin, P.A.S. (2019). Chemical Senses in Feeding, Belonging, and Surviving or Are You Going to Eat That? Cambridge Elements -- Perception. 1-45. ISBN: 978-1-108-71407-5 (PB).
• Type: Journal Articles Status: Published Year Published: 2019 Citation: Hwang, L.D., Lin, C., Gharahkhani, P., Cuellar-Partida, G., Ong, J.S., An, J., Gordon, S.D., Zhu, G., MacGregor, S., Lawlor, D.A., Breslin, P.A.S., Wright, M.J., Martin, N.G., Reed, D.R. (2019). New insight into human sweet taste: a genome-wide association study of the perception and intake of sweet substances. Am J Clin Nutr. 109: 1724- 1737. PMID: 31005972
• Type: Journal Articles Status: Published Year Published: 2019 Citation: Goren, L., Zhang, G., Kaushik, S., Breslin, P.A.S., Du, Y.N., Foster, D.A. (2019). (-)-Oleocanthal and (-)-oleocanthal-rich olive oils induce lysosomal membrane permeabilization in cancer cells. PLoS One. 14(8):e0216024. PMID: 31412041

Progress 10/01/17 to 09/30/18

Outputs
Target Audience:Target audiences include individuals, groups, market segments, or communities that were served by the project. Also included are population groups such as racial and ethnic minorities and those who are socially, economically, or educationally disadvantaged. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?As I was on sabbatical in the prior year, I had no students and so there were no training opportunities during that period. How have the results been disseminated to communities of interest?Through peer reviewed publications What do you plan to do during the next reporting period to accomplish the goals?We will be examining the role of oral enzymes, both salivary and membrane bound, to provide mono-saccharides from disaccharides and starches, that can be utilized to generate metabolic signals orally. These cannot exist without these oral enzymes as larger molecules and disaccarides cannot be transported into cells to yield a metabolic signal.

Impacts
What was accomplished under these goals? Consumption of coffee, tea and alcohol might be shaped by individual differences in bitter taste perception, but inconsistent observational findings provide little insight regarding causality. This research conducted Mendelian randomization analyses using genetic variants associated with the perception of bitter substances (rs1726866 for propylthiouracil [PROP], rs10772420 for quinine and rs2597979 for caffeine) to evaluate the intake of coffee, tea and alcohol among up to 438,870 UK Biobank participants. A standard deviation (SD) higher in genetically predicted bitterness of caffeine was associated with increased coffee intake (0.146 [95%CI: 0.103, 0.189] cups/day), whereas a SD higher in those of PROP and quinine was associated with decreased coffee intake (-0.021 [-0.031, -0.011] and -0.081 [-0.108, -0.054] cups/day respectively). Higher caffeine perception was also associated with increased risk of being a heavy (>4 cups/day) coffee drinker (OR 1.207 [1.126, 1.294]). Opposite pattern of associations was observed for tea possibly due to the inverse relationship between both beverages. Alcohol intake was only negatively associated with PROP perception (-0.141 [-1.88, -0.94] times/month per SD increase in PROP bitterness). Our results reveal that bitter perception is causally associated with intake of coffee, tea and alcohol, suggesting a role of bitter taste in the development of bitter beverage consumption. In another study, we most recently determined that the presence of glucose orally alters liking and preference for oral stimuli and foods and this can be enhanced by addition of the K-ATP channel blocker tolbutamide as an oral rinse which enhances oral metabolic signaling. This was done in a sample population of human volunteers and tested both with a vehicle control and a negative control in duplicate. The effects were robust and significant. This has implications for human liking, wanting, and preference of foods.

Publications

• Type: Journal Articles Status: Published Year Published: 2018 Citation: Ong JS, Hwang DL, Zhong VW, An J, Gharahkhani P, Breslin PAS, Wright MJ, Lawlor DA, Whitfield J, MacGregor S, Martin NG, Cornelis MC. Understanding the role of bitter taste perception in coffee, tea and alcohol consumption through Mendelian randomization. Sci Rep. 2018 Nov 15;8(1):16414. doi: 10.1038/s41598-018-34713-z.
• Type: Journal Articles Status: Published Year Published: 2018 Citation: Hwang LD, Gharahkhani P, Breslin PAS, Gordon SD, Zhu G, Martin NG, Reed DR, Wright MJ. Bivariate genome-wide association analysis strengthens the role of bitter receptor clusters on chromosomes 7 and 12 in human bitter taste. BMC Genomics. 2018 Sep 17;19(1):678. doi: 10.1186/s12864-018-5058-2.

Progress 10/01/16 to 09/30/17

Outputs
Target Audience:Target audiences include individuals, groups, market segments, or communities that were served by the project. Also included are population groups such as racial and ethnic minorities and those who are socially, economically, or educationally disadvantaged. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?This project has provided the opportunity for one PhD student and one PhD candidate, as well as one undergraduate students. Both graduate students have presented their research at their University and at professional conferences. How have the results been disseminated to communities of interest?Publications in peer reviewed journal and a lay book about neuroscience. What do you plan to do during the next reporting period to accomplish the goals?We plan to continue psychophysical testing to assess metabolic responses to oral glucose with and without T1R agonists and antagonists added. The focus of this next phase will be to address whether metabolic sensing affects perceived intensity of sweeteners and/or liking and preference for sweeteners.

Impacts
What was accomplished under these goals? Our objective is to use a psycho-pharmacological approach to understand and to help identify the oral taste receptors for macronutrients including carbohydrates and amino acid receptors. In this past period we focused on topical manipulators of the KATP sensitive ion channel and the oral enzymes that cleave disaccharides into monosaccharides to determine if they affect the perception of the sweetener sucrose. The majority of subjects find that when sucrose cannot be cleaved by oral saccharidases that sucrose is a less effective sweetener. This appears to be due to the fact that sucrose cannot signal metabolically as a disaccharide, as only monosaccharides are transported across mammalian cell membranes. We believe these data not only support a role for metabolic signaling in sugar taste, but also indicate that oral saccharidases are necessary for this to occur and that high fructose corn syrup will differ from sucrose in the metabolic signal generated. This may explain differences observed in perception between sucrose sweetened beverages and high fructose corn sweetener.

Publications

• Type: Journal Articles Status: Published Year Published: 2017 Citation: Kochem, M., Breslin, P.A.S. (2017). Clofibrate Inhibits the Umami-Savory Taste of Glutamate. PLOS One. 12(3): e0172534. https://doi.org/10.1371/journal.pone.0172534. PMID: 28248971

Progress 06/20/16 to 09/30/16

Outputs
Target Audience:Target audiences include individuals, groups, market segments, or communities that were served by the project. Also included are population groups such as racial and ethnic minorities and those who are socially, economically, or educationally disadvantaged. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?This project has provided the opportunity for one PhD student and one PhD candidate, as well as one undergraduate students. Both graduate students have presented their research at their University and at professional conferences. How have the results been disseminated to communities of interest?Publications in peer reviewed journals What do you plan to do during the next reporting period to accomplish the goals?We plan to continue genetic screening and psychophysical testing, both to expand the dataset in place and to broaden the search for genetic influence on perceptual differences in individuals and populations. We also will assess metabolic responses to oral glucose with and without T1R agonists and antagonists added.

Impacts
What was accomplished under these goals? Our objective is to use a psycho-pharmacological approach to understand and to help identify the oral taste receptors for macronutrients including carbohydrates and amino acid receptors. In this study we focused on topical inhibitors of the Class 1 taste receptor, the TAS1Rs, to determine if they inhibit sweet taste of glucose and sucralose. The two compounds we used were lactisole and the blood cholesterol lowering compound clofibrate, which also inhibits T1Rs. The majority of subjects find clofibrate a more effective sweet taste inhibitor than lactisole. But some subjects find lactisole a more effective sweet taste inhibitor than clofibrate. The pharmacological T1R inhibitor clofibrate reduces sweet taste effectively. This class of drug is important for minimizing heart disease and atherosclerosis in patients. But its purported mechanism of action does not involve the T1R receptors. Given that these receptors are expressed throughout the gastro-intestinal tract and are on the pancreas, they play a key role in regulating plasma nutrient levels. Perhaps the action of these drugs on T1R receptors also aids in controlling cholesterol levels. The T1R genes of these subjects are presently being fully sequenced to determine if there are associations between genotype and taste abilities. Their receptors will ultimately be functionally expressed in vitro to determine if mutations in the receptor can account for these perceptual traits.

Publications

• Type: Journal Articles Status: Published Year Published: 2016 Citation: Kochem, M., Breslin, P.A.S. (2016). Lipid-Lowering Pharmaceutical Clofibrate Inhibits Human Sweet Taste. Chem Senses. [Epub ahead of print]. PMID: 27742692
• Type: Journal Articles Status: Published Year Published: 2016 Citation: Hwang, L.-D., Cuellar-Partida, G., Ong, J.-S., Breslin, P.A.S., Reed, D.R., MacGregor, S., Gharahkhani, P., Martin, N.G., Renter�a, M.E. (2016) Sweet taste perception is associated with body mass index at the phenotypic and genotypic level. Twin Res. Hum. Genetics, 19: 465-71. PMID: 27492574.
• Type: Journal Articles Status: Published Year Published: 2016 Citation: Peyrot des Gachons, C. and Breslin, P.A.S. (2016) Salivary Amylase: Digestion and Metabolic Syndrome. Current Diabetes Reports, 16:102. PMID: 27640169
• Type: Journal Articles Status: Published Year Published: 2016 Citation: Hwang, L.D., Breslin, P.A.S., Reed, D.R., Zhu, G., Martin, N.G., Wright, M.J. (2016). Is the Association Between Sweet and Bitter Perception due to Genetic Variation? Chem Senses. [Epub ahead of print] PMID: 27506221
• Type: Journal Articles Status: Published Year Published: 2016 Citation: Peyrot des Gachons, C., Avrillier, J., Gleason, M., Algarra, L., Zhang, S., Mura, E., Nagai, H., Breslin, P.A.S. (2016). Oral Cooling and Carbonation Increase the Perception of Drinking and Thirst Quenching in Thirsty Adults. PLoS One, 29;11(9):e0162261. PMID: 27685093.