Leptin Modulates Behavioral Responses to Sweet Substances by Influencing Peripheral Taste Structures
Abstract
Leptin is a hormone that regulates body weight homeostasis mainly via the hypothalamic functional leptin receptor Ob-Rb. Recently, we proposed that the taste organ is a new peripheral target for leptin. Leptin selectively inhibits mouse taste cell responses to sweet substances and thereby may act as a sweet taste modulator. The present study further investigated leptin action on the taste system by examining expression of Ob-Rb in taste cells and behavioral responses to sweet substances in leptin-deficient ob/ob, and Ob-Rb-deficient db/db mice and their normal litter mates. RT-PCR analysis showed that Ob-Rb was expressed in taste cells in all strains tested. The db/db mice, however, had a RT-PCR product containing an abnormal db insertion that leads to an impaired shorter intracellular domain. In situ hybridization analysis showed that the hybridization signals for normal Ob-Rb mRNA were detected in taste cells in lean and ob/ob mice but not in db/db mice. Two different behavioral tests, one using sweet-bitter mixtures as taste stimuli and the other a conditioned taste aversion paradigm, demonstrated that responses to sucrose and saccharin were significantly decreased after ip injection of leptin in ob/ob and normal littermates, but not in db/db mice. These results suggest that leptin suppresses behavioral responses to sweet substances through its action on Ob-Rb in taste cells. Such taste modulation by leptin may be involved in regulation for food intake.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In rodents, absence of leptin increases and addition of leptin dampens peripheral taste and olfactory sensitivity.
“In rodents, absence of leptin has been shown to increase and addition of leptin to dampen peripheral taste and olfactory sensitivity”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [157]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419 · see citing works
Campfield, L. A., Smith, F. J., Guisez, Y., Devos, R., & Burn, P. (1995) · Science · doi:10.1126/science.7624778 · Cited by 3,243 · see citing works
Abnormal splicing of the leptin receptor in diabetic mice
Lee, G.-H., Proenca, R., Montez, J. M., Carroll, K. M., Darvishzadeh, J. G., Lee, J. I., & Friedman, J. M. (1996) · Nature · doi:10.1038/379632a0 · Cited by 2,327 · see citing works
Chen, H., Charlat, O., Tartaglia, L. A., Woolf, E. A., Weng, X., Ellis, S. J., Lakey, N. D., Culpepper, J., More, K. J., Breitbart, R. E., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81294-5 · Cited by 2,214 · see citing works
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1995) · Nature · doi:10.1038/374479a0 · Cited by 1,125 · see citing works
Divergent Signaling Capacities of the Long and Short Isoforms of the Leptin Receptor
Bjørbæk, C., Uotani, S., da Silva, B., & Flier, J. S. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.51.32686 · Cited by 890 · see citing works
Defective STAT signaling by the leptin receptor in diabetic mice.
Ghilardi, N., Ziegler, S., Wiestner, A. C., Stoffel, R., Heim, M. H., & Skoda, R. C. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.13.6231 · Cited by 793 · see citing works
Gustducin is a taste-cell-specific G protein closely related to the transducins
McLaughlin, S. K., McKinnon, P. J., & Margolskee, R. F. (1992) · Nature · doi:10.1038/357563a0 · Cited by 679 · see citing works
Biotin amplification of biotin and horseradish peroxidase signals in histochemical stains.
Adams, J. C. (1992) · Journal of Histochemistry & Cytochemistry · doi:10.1177/40.10.1527370 · Cited by 644 · see citing works
Barrachina, M. D., Martínez, V., Wang, L., Wei, J. Y., & Taché, Y. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.19.10455 · Cited by 440 · see citing works
Leptin Receptors Expressed on Pancreatic β-Cells
Kieffer, T. J., Heller, R. S., & Habener, J. F. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1059 · Cited by 326 · see citing works
Leptin as a modulator of sweet taste sensitivities in mice
Kawai, K., Sugimoto, K., Nakashima, K., Miura, H., & Ninomiya, Y. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.190066697 · Cited by 321 · see citing works
Self-citationHoggard, N., Mercer, J. G., Rayner, D. V., Moar, K. M., Trayhurn, P., & Williams, L. M. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6245 · Cited by 297 · see citing works
Takaya, K., Ogawa, Y., Isse, N., Okazaki, T., Satoh, N., Masuzaki, H., Mori, K., Tamura, N., Hosoda, K., & Nakao, K. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1133 · Cited by 263 · see citing works
Central leptin modulates behavioral and neural responsivity to CCK
Emond, M. H., Schwartz, G. J., Ladenheim, E. E., & Moran, T. H. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.276.5.r1545 · Cited by 225 · see citing works
Brain Stem Is a Direct Target for Leptin’s Action in the Central Nervous System
Hosoi, T., Kawagishi, T., Okuma, Y., Tanaka, J., & Nomura, Y. (2002) · Endocrinology · doi:10.1210/en.2002-220077 · Cited by 205 · see citing works
Evidence for neural inhibition in bittersweet taste mixtures.
Lawless, H. T. (1979) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0077582 · Cited by 189 · see citing works
Bitterness suppression as revealed by split-tongue taste stimulation in humans
Kroeze, J. H. A., & Bartoshuk, L. M. (1985) · Physiology & Behavior · doi:10.1016/0031-9384(85)90412-3 · Cited by 144 · see citing works
Leptin Receptor Signal Transduction: OBRa and OBRb offaType
Yamashita, T., Murakami, T., Otani, S., Kuwajima, M., & Shima, K. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8689 · Cited by 139 · see citing works
Schwartz, G. J., & Moran, T. H. (2002) · Endocrinology · doi:10.1210/en.2002-220352 · Cited by 120 · see citing works
Gustatory neural responses in preweanling mice
Ninomiya, Y., Tanimukai, T., Yoshida, S., et al. (1991) · Physiology & Behavior · doi:10.1016/0031-9384(91)90203-z · Cited by 76 · see citing works
Self-citationQualitative discrimination of gustatory stimuli in three different strains of mice
Ninomiya, Y., Higashi, T., Katsukawa, H., et al. (1984) · Brain Research · doi:10.1016/0006-8993(84)91183-1 · Cited by 70 · see citing works
Self-citationEnhanced gustatory neural responses to sugars in the diabetic db/db mouse
Ninomiya, Y., Sako, N., & Imai, Y. (1995) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1995.269.4.r930 · Cited by 59 · see citing works
Self-citationNinomiya, Y., Shigemura, N., Yasumatsu, K., Ohta, R., Sugimoto, K., Nakashima, K., & Lindemann, B. (2002) · Vitamins and hormones · doi:10.1016/s0083-6729(02)64007-5 · Cited by 48 · see citing works
Self-citationBreininger, J. F., & Baskin, D. G. (2000) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215540004801202 · Cited by 40 · see citing works
Opponent effects of quinine and sucrose on single fiber taste responses of the chorda tympani nerve
Formaker, B. K., MacKinnon, B. I., Hettinger, T. P., & Frank, M. E. (1997) · Brain Research · doi:10.1016/s0006-8993(97)00845-7 · Cited by 39 · see citing works
Gurmarin Suppression of Licking Responses to Sweetener-Quinine Mixtures in C57BL Mice
Murata, Y. (2003) · Chemical Senses · doi:10.1093/chemse/28.3.237 · Cited by 33 · see citing works
Enhanced responses of the chorda tympani nerve to nonsugar sweeteners in the diabeticdb/dbmouse
Ninomiya, Y., Imoto, T., Yatabe, A., et al. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.274.5.r1324 · Cited by 28 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
How Palatable Food Disrupts Appetite Regulation
Erlanson‐Albertsson, C. (2005) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/j.1742-7843.2005.pto_179.x · Cited by 330 · see citing works
Vagal and hormonal gut-brain communication: from satiation to satisfaction
Berthoud, H. ‐. (2008) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2008.01104.x · Cited by 307 · see citing works
Food reward, hyperphagia, and obesity
Berthoud, H.-R., Lenard, N. R., & Shin, A. C. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00028.2011 · Cited by 275 · see citing works
Nakamura, Y., Sanematsu, K., Ohta, R., Shirosaki, S., Koyano, K., Nonaka, K., Shigemura, N., & Ninomiya, Y. (2008) · Diabetes · doi:10.2337/db07-1103 · Cited by 161 · see citing works
Self-citationModulation of taste responsiveness and food preference by obesity and weight loss
Berthoud, H.-R., & Zheng, H. (2012) · Physiology & Behavior · doi:10.1016/j.physbeh.2012.04.004 · Cited by 123 · see citing works
Leptin regulates olfactory-mediated behavior in ob/ob mice
Getchell, T. V., Kwong, K., Saunders, C. P., Stromberg, A. J., & Getchell, M. L. (2006) · Physiology & Behavior · doi:10.1016/j.physbeh.2005.11.016 · Cited by 96 · see citing works
Expression of Renin-Angiotensin System Components in the Taste Organ of Mice
Shigemura, N., Takai, S., Hirose, F., Yoshida, R., Sanematsu, K., & Ninomiya, Y. (2019) · Nutrients · doi:10.3390/nu11092251 · Cited by 65 · see citing works
Self-citation
- Authors
- Shigemura, N., Ohta, R., Kusakabe, Y., Miura, H., Hino, A., Koyano, K., Nakashima, K., & Ninomiya, Y.
- Affiliations
- Kyushu University (JP)
- National Agriculture and Food Research Organization (JP)
- Asahi University (JP)
- Corresponding author
- Ninomiya, Yuzo
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2004-02
- Volume
- 145
- Issue
- 2
- Pages
- 839-847
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2053252677
- Cited by
- 199
- References
- 28
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 4 · 2020: 8 · 2019: 13 · 2018: 5 · 2017: 24 · 2016: 10 · 2015: 8 · 2014: 9 · 2013: 8 · 2012: 15
- FWCI
- 4.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (15209061, 12470394)
- Bio-oriented Technology Research Advancement Institution
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Biochemical Analysis and Sensing Techniques
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- leptin, sweet taste, taste cells, Ob-Rb, leptin receptor, taste modulation, conditioned taste aversion, sucrose, saccharin, ob/ob mice, db/db mice, food intake regulation
- MeSH terms
- Animals, Behavior, Animal, Diabetes Mellitus, Female, Male, Mice, Inbred C57BL, Mice, Obese, Receptors, Cell Surface, RNA, Messenger, Saccharin, Sucrose, Taste, Taste Buds, Gene Expression, In Situ Hybridization, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Leptin, Mice, Receptors, Leptin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
