Diurnal Variation of Human Sweet Taste Recognition Thresholds Is Correlated With Plasma Leptin Levels
Open accessAbstract
OBJECTIVE—It has recently been proposed that the peripheral taste organ is one of the targets for leptin. In lean mice, leptin selectively suppresses gustatory neural and behavioral responses to sweet compounds without affecting responses to other taste stimuli, whereas obese diabetic db/db mice with defects in leptin receptor lack this leptin suppression on sweet taste. Here, we further examined potential links between leptin and sweet taste in humans. RESEARCH DESIGN AND METHODS—A total of 91 nonobese subjects were used to determine recognition thresholds using a standard stair-case methodology for various taste stimuli. Plasma leptin levels were determined by an enzyme-linked immunosorbent assay at several timepoints during the day under normal and restricted-meal conditions. RESULTS—The recognition thresholds for sweet compounds exhibited a diurnal variation from 0800 to 2200 h that parallels variation for leptin levels, with the lowest thresholds in the morning and the highest thresholds at night. This diurnal variation is sweet-taste selective—it was not observed in thresholds for other taste stimuli (NaCl, citric acid, quinine, and mono-sodium glutamate). The diurnal variation for sweet thresholds in the normal feeding condition (three meals) was independent of meal timing and thereby blood glucose levels. Furthermore, when leptin levels were phase-shifted following imposition of one or two meals per day, the diurnal variation of thresholds for sweet taste shifted in parallel. CONCLUSIONS—This synchronization of diurnal variation in leptin levels and sweet taste recognition thresholds suggests a mechanistic connection between these two variables in humans.
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The recognition thresholds for sweet compounds also show a daily variation.
“In addition, the recognition thresholds for sweet compounds also showed a daily variation [89].”
From Human thermal perception and time of day: A review (2021) · cites this paper as [89]
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Brandauer, J., Landers‐Ramos, R. Q., Jenkins, N. T., Spangenburg, E. E., Hagberg, J. M., & Prior, S. J. (2013) · Physiological Reports · doi:10.1002/phy2.40 · Cited by 33 · see citing works
“Previous studies have reported early-morning reductions in circulating leptin concentrations so it is possible that the decreases in leptin we observed could at least be partly due to diurnal variations (Nakamura et al. 2008).”
BackgroundPioltine, M. B., de Melo, M. E., Santos, A. S., Machado, A. D., Fernandes, A. E., Fujiwara, C. T. H., Cercato, C., & Mancini, M. C. (2018) · Journal of Personalized Medicine · doi:10.3390/jpm8010007 · Cited by 30 · see citing works
“This indicates that this hormone can be a modulator of the perception of the sweet taste, with a direct action in the regulation of the dietary intake [28].”
BackgroundSalivary α-Amylase Activity and Starch-Related Sweet Taste Perception in Humans
Aji, G. K., Warren, F. J., & Roura, E. (2019) · Chemical Senses · doi:10.1093/chemse/bjz010 · Cited by 31 · see citing works
Physiology of Taste Processing in the Tongue, Gut, and Brain
Gutiérrez, R., & Simon, S. A. (2021) · Comprehensive physiology · doi:10.1002/cphy.c210002 · Cited by 30 · see citing works
Sweet and Umami Taste Perception Differs with Habitual Exercise in Males
Feeney, E. L., Leacy, L., O’Kelly, M., Leacy, N., Phelan, A., Crowley, L., Stynes, E., de Casanove, A., & Horner, K. M. (2019) · Nutrients · doi:10.3390/nu11010155 · Cited by 29 · see citing works
“For example, leptin can inhibit the response to sweet taste [10,44].”
BackgroundExplaining diurnal patterns of food consumption
Spence, C. J. (2021) · Food Quality and Preference · doi:10.1016/j.foodqual.2021.104198 · Cited by 27 · see citing works
Reciprocal Modulation of Sweet Taste by Leptin and Endocannabinoids
Niki, M., Jyotaki, M., Yoshida, R., & Ninomiya, Y. (2010) · Results and problems in cell differentiation · doi:10.1007/978-3-642-14426-4_9 · Cited by 25 · see citing works
Self-citationPerceptual and Neural Responses to Sweet Taste in Humans and Rodents
Lemon, C. H. (2015) · Chemosensory Perception · doi:10.1007/s12078-015-9177-8 · Cited by 25 · see citing works
“Associations between psychophysical and neurophysiological data have provided insight into potential mechanistic relationships between neural circuitry and perceptual phenomena in diverse systems (e.g., LaMotte and Campbell 1978; Newsome et al. 1989).”
BackgroundNutrient-Sensing Biology in Mammals and Birds
Roura, E., & Foster, S. R. (2017) · Annual Review of Animal Biosciences · doi:10.1146/annurev-animal-030117-014740 · Cited by 25 · see citing works
“In particular, a negative association between circulating leptin levels and sweet taste sensitivity has been reported in mice and humans (180, 181).”
BackgroundTemporal patterns in taste sensitivity
Costanzo, A. (2023) · Nutrition Reviews · doi:10.1093/nutrit/nuad097 · Cited by 24 · see citing works
“Overall, there appears to be some evidence for umami taste sensitivity being regulated by food intake in humans 30 and mice.”
BackgroundResultInfluentialThe Effect of Short, Daily Oral Exposure on Non-esterified Fatty Acid Sensitivity
Tucker, R. M., Laguna, L., Quinn, R. L., & Mattes, R. D. (2013) · Chemosensory Perception · doi:10.1007/s12078-013-9147-y · Cited by 23 · see citing works
Making Circadian Cancer Therapy Practical
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Diurnal Variation of Sweet Taste Recognition Thresholds Is Absent in Overweight and Obese Humans
Sanematsu, K., Nakamura, Y., Nomura, M., Shigemura, N., & Ninomiya, Y. (2018) · Nutrients · doi:10.3390/nu10030297 · Cited by 20 · see citing works
“Consistent with our previous report on NW subjects [5], a significant gender difference was observed in plasma leptin levels (p < 0.”
InfluentialSelf-citationSugars, sweet taste receptors, and brain responses
Lee, A. A., & Owyang, C. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-849886-6.00020-3 · Cited by 20 · see citing works
Single bright light exposure decreases sweet taste threshold in healthy volunteers
Srivastava, S., Donaldson, L. F., Rai, D., Melichar, J., & Potokar, J. P. (2013) · Journal of Psychopharmacology · doi:10.1177/0269881113499206 · Cited by 19 · see citing works
Variation in the Sweet Taste Receptor Gene and Dietary Intake in a Swedish Middle-Aged Population
Habberstad, C., Drake, I., & Sonestedt, E. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00348 · Cited by 18 · see citing works
“Studies have shown that leptin, which is produced by adipocytes and regulates food intake and body weight, can affect sugar sensitivity by interacting with sweet taste receptors (26).”
BackgroundBelzer, L. M., Smulian, J. C., Lu, S., & Tepper, B. J. (2009) · Chemical Senses · doi:10.1093/chemse/bjp041 · Cited by 18 · see citing works
“Also of relevance are recent data from nondiabetic humans showing that changes in sweet taste recognition thresholds are synchronized with the diurnal variation in leptin (Nakamura et al. 2008).”
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Li, W.-L., Chen, M., Liu, S., Li, G., Gu, T.-Y., Liang, P., Qin, Y., Zhan, Y.-H., Quan, Y., & Zhang, G. (2013) · Journal of Molecular Neuroscience · doi:10.1007/s12031-013-0011-y · Cited by 17 · see citing works
Endogenous Peripheral Neuromodulators of the Mammalian Taste Bud
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“…recent series of excellent publications, investigators at the Ninomiya laboratory have reported studies that detailed interactions of both leptin (Kawai et al. 2000; Nakamura et al. 2008) and a variety of endocannabinoids (Yoshida et al. 2010), with receptors located peripherally, in the taste bud.”
BackgroundChatterjee, A., & Hardin, P. E. (2010) · Fly · doi:10.4161/fly.4.4.13010 · Cited by 15 · see citing works
Leptin's Effect on Taste Bud Calcium Responses and Transmitter Secretion
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“Further, diurnal variations in circulating plasma leptin levels have been correlated with sweet taste thresholds in humans (Nakamura et al. 2008) and mice (Kawai et al.”
BackgroundPhosphatidylinositol‐3 kinase mediates the sweet suppressive effect of leptin in mouse taste cells
Yoshida, R., Margolskee, R. F., & Ninomiya, Y. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15268 · Cited by 14 · see citing works
“Plasma leptin levels may specifically affect sweet taste sensitivity in healthy adults (Nakamura et al., 2008), and a decrease in circulating leptin levels is associated with a decrease in sweet taste thresholds during weight loss in obese females (Umabiki et al., 2010).”
BackgroundSelf-citationLeptin suppresses sweet taste responses of enteroendocrine STC-1 cells
Jyotaki, M., Sanematsu, K., Shigemura, N., Yoshida, R., & Ninomiya, Y. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.06.036 · Cited by 13 · see citing works
“Indeed, our previous human study demonstrated that greater post-ingestive rises of blood glucose levels of individuals were correlated with lower leptin levels and higher sweet sensitivities before meal (Nakamura et al., 2008).”
BackgroundSelf-citationDietary proteins and food-related reward signals
Peuhkuri, K., Sihvola, N., & Korpela, R. (2011) · Food & Nutrition Research · doi:10.3402/fnr.v55i0.5955 · Cited by 13 · see citing works
Physiology of Taste Processing in the Tongue, Gut, and Brain
Gutiérrez, R., & Simon, S. A. (2021) · Comprehensive physiology · doi:10.1002/j.2040-4603.2021.tb00188.x · Cited by 12 · see citing works
“Leptin is an anorexigenic peptide produced in adipose tissue that decreases food intake (77, 180).”
Moleküle und biologische Mechanismen des Süß‐ und Umamigeschmacks
Behrens, M., Meyerhof, W., Hellfritsch, C., & Hofmann, T. F. (2011) · Angewandte Chemie · doi:10.1002/ange.201002094 · Cited by 12 · see citing works
Iwamura, M., Honda, R., & Nagasawa, K. (2020) · Nutrients · doi:10.3390/nu12040990 · Cited by 12 · see citing works
“The increase in expression of sweet taste receptors was a rather immediate response under fed conditions following fasting treatment, and this was considered to be due to post-transcriptional regulation of their protein, but not gene expression and satiety-related hormonal regulation such as leptin [26,27] and insulin…”
BackgroundO’Brien, P., Hewett, R., & Corpe, C. P. (2018) · Physiological Genomics · doi:10.1152/physiolgenomics.00139.2017 · Cited by 12 · see citing works
“Previous studies have shown a diurnal rhythm in sweet taste perception (31), carbohydrate digestion (16), sugar transport capacity (2), and in GLP1 secretory response to nutrients (12); however, the molecular mechanisms responsible for the observed rhythmicity remain poorly understood.”
BackgroundModulation and Transmission of Sweet Taste Information for Energy Homeostasis
Sanematsu, K., Horio, N., Murata, Y., Yoshida, R., Ohkuri, T., Shigemura, N., & Ninomiya, Y. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.03893.x · Cited by 12 · see citing works
Self-citationTongue Leptin Decreases Oro-Sensory Perception of Dietary Fatty Acids
Ullah, H., Khan, A. S., Murtaza, B., Hichami, A., & Khan, N. A. (2021) · Nutrients · doi:10.3390/nu14010197 · Cited by 10 · see citing works
“It is i portant to entio that circulating plasma leptin evels have been correlated with alterations in taste threshold in uman be gs [15] and rodents [16].”
BackgroundMyers, T. R., Saul, B., Karlsen, M., Beauchesne, A. R., Glavas, Z., Ncube, M., Bradley, R. D., & Goldhamer, A. C. (2022) · Cureus · doi:10.7759/cureus.24689 · Cited by 10 · see citing works
“Additionally, sweet taste sensitivity, but not salty, sour, bitter, or umami, varies throughout the day with lower RTs observed in the morning and higher RTs at night in a pattern that is positively correlated with leptin levels and negatively correlated with blood glucose levels [29].”
BackgroundInfluencia genética en las preferencias alimentarias
Ramos-López, O., Ojeda‐Granados, C., Román, S., & Panduro, A. (2013) · Revista de Endocrinología y Nutrición · Cited by 10 · see citing works
Sweet Taste: From Reception to Perception
Murovets, V. O., Lukina, E. A., & Zolotarev, V. A. (2024) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-024-01658-y · Cited by 10 · see citing works
“Some peptides from taste buds may enter the brain or peripheral organs, while taste cell receptors respond to circulating hormones, i.e., taste responses may depend on the metabolic status of the body or may prepare the body to process consumed nutrients or toxins [31, 92, 106, 130, 168, 169, 183].”
Carbohydrate Taste Is Associated with Food Intake and Body Mass in Healthy Australian Adults
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Hormones and bioactive substances that affect peripheral taste sensitivity
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Peptide Signaling in Taste Transduction
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“Blood glucose and insulin levels after lunch have been reported to be signi fi cantly higher after breakfast deprivation than after breakfast consumption 18 .”
BackgroundObjective and Subjective Aspects of the Drive to Eat in Obesogenic Environments
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Sensitivity to Sweet and Salty Tastes in Children and Adolescents with Type 1 Diabetes
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“carbohydrates than their healthy peers [29].”
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“45 Other hormones like glucagon-like-peptide (GLP-1), oxytocin, and insulin also seem to affect taste buds and therefore gustatory function.”
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- Authors
- Nakamura, Y., Sanematsu, K., Ohta, R., Shirosaki, S., Koyano, K., Nonaka, K., Shigemura, N., & Ninomiya, Y.
- Affiliations
- Kyushu University (JP)
- Corresponding author
- Ninomiya, Yuzo
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2008-10-01
- Volume
- 57
- Issue
- 10
- Pages
- 2661-2665
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC2551675
- OpenAlex
- W2128451984
- Cited by
- 161
- References
- 21
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 6 · 2023: 5 · 2022: 9 · 2021: 12 · 2020: 10 · 2019: 13 · 2018: 9 · 2017: 10 · 2016: 8 · 2015: 8 · 2014: 7 · 2013: 11 · 2012: 12
- FWCI
- 8.53
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Biochemical Analysis and Sensing Techniques
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Keywords
- leptin, sweet taste, taste recognition threshold, diurnal variation, plasma leptin, meal timing, leptin receptor, taste perception, circadian rhythm
- MeSH terms
- Adult, Circadian Rhythm, Female, Humans, Insulin, Male, Quinine, Sodium Chloride, Sodium Glutamate, Taste Buds, Taste Threshold, Citric Acid, Leptin, Young Adult
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