Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

PNAS 97 (20): 11044-11049

Copyright © 2000 by the National Academy of Sciences.


BIOLOGICAL SCIENCES / NEUROBIOLOGY

Leptin as a modulator of sweet taste sensitivities in mice

Kirio Kawai*, Kumiko Sugimoto*, Kiyohito Nakashima{dagger}, Hirohito Miura{ddagger}, and Yuzo Ninomiya§

*Section of Molecular Neurobiology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan; {dagger}Department of Chemistry, Asahi University School of Dentistry, 1851-1 Hozumi, Motosu-gun, Gifu 501-0296, Japan; {ddagger}National Food Research Institute, Ministry of Agriculture, Forestry, and Fisheries, 2-1-2 Kannondai, Tsukuba, Ibaraki 305-8642, Japan; and §Section of Oral Neuroscience, Faculty of Dentistry, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka-Pref. 812-8582, Japan

Received for publication February 15, 2000.

Abstract: Leptin acts as a potent inhibitory factor against obesity by regulating energy expenditure, food intake, and adiposity. The obese diabetic db/db mouse, which has defects in leptin receptor, displays enhanced neural responses and elevated behavioral preference to sweet stimuli. Here, we show the effects of leptin on the peripheral taste system. An administration of leptin into lean mice suppressed responses of peripheral taste nerves (chorda tympani and glossopharyngeal) to sweet substances (sucrose and saccharin) without affecting responses to sour, salty, and bitter substances. Whole-cell patch-clamp recordings of activities of taste receptor cells isolated from circumvallate papillae (innervated by the glossopharyngeal nerve) demonstrated that leptin activated outward K+ currents, which resulted in hyperpolarization of taste cells. The db/db mouse with impaired leptin receptors showed no such leptin suppression. Taste tissue (circumvallate papilla) of lean mice expressed leptin-receptor mRNA and some of the taste cells exhibited immunoreactivities to antibodies of the leptin receptor. Taken together, these observations suggest that the taste organ is a peripheral target for leptin, and that leptin may be a sweet-sensing modulator (suppressor) that may take part in regulation of food intake. Defects in this leptin suppression system in db/db mice may lead to their enhanced peripheral neural responses and enhanced behavioral preferences for sweet substances.


To whom reprint requests should be addressed. E-mail: nino{at}dent.kyushu-u.ac.jp.

Edited by Dale Purves, Duke University Medical Center, Durham, NC, and approved July 19, 2000

This paper was submitted directly (Track II) to the PNAS office.

Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.190066697.

Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.190066697

|| Kinnamon, S. C. & Varkevisser, B. (1999) Chem. Senses 24, 84 (abstr.).

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Longitudinal Analysis of Calorie Restriction on Rat Taste Bud Morphology and Expression of Sweet Taste Modulators.
H. Cai, C. M. Daimon, W.-n. Cong, R. Wang, P. Chirdon, R. de Cabo, J. Sevigny, S. Maudsley, and B. Martin (2014)
J Gerontol A Biol Sci Med Sci 69, 532-544
   Abstract »    Full Text »    PDF »
Endogenous Gustatory Responses and Gene Expression Profile of Stably Proliferating Human Taste Cells Isolated From Fungiform Papillae.
A. Hochheimer, M. Krohn, K. Rudert, K. Riedel, S. Becker, C. Thirion, and H. Zinke (2014)
Chem Senses 39, 359-377
   Abstract »    Full Text »    PDF »
Taste receptors of the gut: emerging roles in health and disease.
I. Depoortere (2014)
Gut 63, 179-190
   Abstract »    Full Text »    PDF »
Modulation of taste responsiveness by the satiation hormone peptide YY.
M. S. La Sala, M. D. Hurtado, A. R. Brown, D. V. Bohorquez, R. A. Liddle, H. Herzog, S. Zolotukhin, and C. D. Dotson (2013)
FASEB J 27, 5022-5033
   Abstract »    Full Text »    PDF »
Obesity alters the gustatory perception of lipids in the mouse: plausible involvement of lingual CD36.
M. Chevrot, A. Bernard, D. Ancel, M. Buttet, C. Martin, S. Abdoul-Azize, J.-F. Merlin, H. Poirier, I. Niot, N. A. Khan, et al. (2013)
J. Lipid Res. 54, 2485-2494
   Abstract »    Full Text »    PDF »
Angiotensin II Modulates Salty and Sweet Taste Sensitivities.
N. Shigemura, S. Iwata, K. Yasumatsu, T. Ohkuri, N. Horio, K. Sanematsu, R. Yoshida, R. F. Margolskee, and Y. Ninomiya (2013)
J. Neurosci. 33, 6267-6277
   Abstract »    Full Text »    PDF »
Taste responses in mice lacking taste receptor subunit T1R1.
Y. Kusuhara, R. Yoshida, T. Ohkuri, K. Yasumatsu, A. Voigt, S. Hubner, K. Maeda, U. Boehm, W. Meyerhof, and Y. Ninomiya (2013)
J. Physiol. 591, 1967-1985
   Abstract »    Full Text »    PDF »
Differences in taste sensitivity between obese and non-obese children and adolescents.
J. Overberg, T. Hummel, H. Krude, and S. Wiegand (2012)
Arch. Dis. Child. 97, 1048-1052
   Abstract »    Full Text »    PDF »
Mechanisms for Sweetness.
J. D. Fernstrom, S. D. Munger, A. Sclafani, I. E. de Araujo, A. Roberts, and S. Molinary (2012)
J. Nutr. 142, 1134S-1141S
   Abstract »    Full Text »    PDF »
Age-Related Changes in Mouse Taste Bud Morphology, Hormone Expression, and Taste Responsivity.
Y.-K. Shin, W.-n. Cong, H. Cai, W. Kim, S. Maudsley, J. M. Egan, and B. Martin (2012)
J Gerontol A Biol Sci Med Sci 67A, 336-344
   Abstract »    Full Text »    PDF »
Umami taste in mice uses multiple receptors and transduction pathways.
K. Yasumatsu, Y. Ogiwara, S. Takai, R. Yoshida, K. Iwatsuki, K. Torii, R. F. Margolskee, and Y. Ninomiya (2012)
J. Physiol. 590, 1155-1170
   Abstract »    Full Text »    PDF »
Adenosine Enhances Sweet Taste through A2B Receptors in the Taste Bud.
R. Dando, G. Dvoryanchikov, E. Pereira, N. Chaudhari, and S. D. Roper (2012)
J. Neurosci. 32, 322-330
   Abstract »    Full Text »    PDF »
Brain Structure Correlates of Individual Differences in the Acquisition and Inhibition of Conditioned Fear.
C. A. Hartley, B. Fischl, and E. A. Phelps (2011)
Cereb Cortex 21, 1954-1962
   Abstract »    Full Text »    PDF »
Genetic variation in TAS1R2 (Ile191Val) is associated with consumption of sugars in overweight and obese individuals in 2 distinct populations.
K. M. Eny, T. M. Wolever, P. N. Corey, and A. El-Sohemy (2010)
Am J Clin Nutr 92, 1501-1510
   Abstract »    Full Text »    PDF »
Endogenous Peripheral Neuromodulators of the Mammalian Taste Bud.
R. Dando (2010)
J Neurophysiol 104, 1835-1837
   Abstract »    Full Text »    PDF »
Gastric bypass surgery alters behavioral and neural taste functions for sweet taste in obese rats.
A. Hajnal, P. Kovacs, T. Ahmed, K. Meirelles, C. J. Lynch, and R. N. Cooney (2010)
Am J Physiol Gastrointest Liver Physiol 299, G967-G979
   Abstract »    Full Text »    PDF »
Glucagon signaling modulates sweet taste responsiveness.
A. E. T. Elson, C. D. Dotson, J. M. Egan, and S. D. Munger (2010)
FASEB J 24, 3960-3969
   Abstract »    Full Text »    PDF »
Review series: The cell biology of taste.
N. Chaudhari and S. D. Roper (2010)
J. Cell Biol. 190, 285-296
   Abstract »    Full Text »    PDF »
Taste Preference for Fatty Acids Is Mediated by GPR40 and GPR120.
C. Cartoni, K. Yasumatsu, T. Ohkuri, N. Shigemura, R. Yoshida, N. Godinot, J. le Coutre, Y. Ninomiya, and S. Damak (2010)
J. Neurosci. 30, 8376-8382
   Abstract »    Full Text »    PDF »
Vasoactive Intestinal Peptide-Null Mice Demonstrate Enhanced Sweet Taste Preference, Dysglycemia, and Reduced Taste Bud Leptin Receptor Expression.
B. Martin, Y. K. Shin, C. M. White, S. Ji, W. Kim, O. D. Carlson, J. K. Napora, W. Chadwick, M. Chapter, J. A. Waschek, et al. (2010)
Diabetes 59, 1143-1152
   Abstract »    Full Text »    PDF »
Endocannabinoids selectively enhance sweet taste.
R. Yoshida, T. Ohkuri, M. Jyotaki, T. Yasuo, N. Horio, K. Yasumatsu, K. Sanematsu, N. Shigemura, T. Yamamoto, R. F. Margolskee, et al. (2010)
PNAS 107, 935-939
   Abstract »    Full Text »    PDF »
Changes in Sweet Taste Across Pregnancy in Mild Gestational Diabetes Mellitus: Relationship to Endocrine Factors.
L. M. Belzer, J. C. Smulian, S.-E. Lu, and B. J. Tepper (2009)
Chem Senses 34, 595-605
   Abstract »    Full Text »    PDF »
Regionally Specific Cortical Thinning in Children with Sickle Cell Disease.
G. R. Kirk, M. R. Haynes, S. Palasis, C. Brown, T. G. Burns, M. McCormick, and R. A. Jones (2009)
Cereb Cortex 19, 1549-1556
   Abstract »    Full Text »    PDF »
Patterns of cortical thinning in the language variants of frontotemporal lobar degeneration.
J. D. Rohrer, J. D. Warren, M. Modat, G. R. Ridgway, A. Douiri, M. N. Rossor, S. Ourselin, and N. C. Fox (2009)
Neurology 72, 1562-1569
   Abstract »    Full Text »    PDF »
Altered Pontine Taste Processing in a Rat Model of Obesity.
P. Kovacs and A. Hajnal (2008)
J Neurophysiol 100, 2145-2157
   Abstract »    Full Text »    PDF »
Diurnal Variation of Human Sweet Taste Recognition Thresholds Is Correlated With Plasma Leptin Levels.
Y. Nakamura, K. Sanematsu, R. Ohta, S. Shirosaki, K. Koyano, K. Nonaka, N. Shigemura, and Y. Ninomiya (2008)
Diabetes 57, 2661-2665
   Abstract »    Full Text »    PDF »
The taste transduction channel TRPM5 is a locus for bitter-sweet taste interactions.
K. Talavera, K. Yasumatsu, R. Yoshida, R. F. Margolskee, T. Voets, Y. Ninomiya, and B. Nilius (2008)
FASEB J 22, 1343-1355
   Abstract »    Full Text »    PDF »
Abnormal Taste Perception in Mice Lacking the Type 3 Inositol 1,4,5-Trisphosphate Receptor.
C. Hisatsune, K. Yasumatsu, H. Takahashi-Iwanaga, N. Ogawa, Y. Kuroda, R. Yoshida, Y. Ninomiya, and K. Mikoshiba (2007)
J. Biol. Chem. 282, 37225-37231
   Abstract »    Full Text »    PDF »
Regulation of feeding behaviour and locomotor activity by takeout in Drosophila.
N. Meunier, Y. H. Belgacem, and J.-R. Martin (2007)
J. Exp. Biol. 210, 1424-1434
   Abstract »    Full Text »    PDF »
Taste Responsiveness of Fungiform Taste Cells With Action Potentials.
R. Yoshida, N. Shigemura, K. Sanematsu, K. Yasumatsu, S. Ishizuka, and Y. Ninomiya (2006)
J Neurophysiol 96, 3088-3095
   Abstract »    Full Text »    PDF »
Trpm5 Null Mice Respond to Bitter, Sweet, and Umami Compounds.
S. Damak, M. Rong, K. Yasumatsu, Z. Kokrashvili, C. A. Perez, N. Shigemura, R. Yoshida, B. Mosinger Jr., J. I. Glendinning, Y. Ninomiya, et al. (2006)
Chem Senses 31, 253-264
   Abstract »    Full Text »    PDF »
Fast Food, Central Nervous System Insulin Resistance, and Obesity.
E. Isganaitis and R. H. Lustig (2005)
Arterioscler Thromb Vasc Biol 25, 2451-2462
   Abstract »    Full Text »    PDF »
Altered taste sensitivity in obese, prediabetic OLETF rats lacking CCK-1 receptors.
A. Hajnal, M. Covasa, and N. T. Bello (2005)
Am J Physiol Regulatory Integrative Comp Physiol 289, R1675-R1686
   Abstract »    Full Text »    PDF »
A new role for leptin as a direct satiety signal from the stomach.
H.-R. Berthoud (2005)
Am J Physiol Regulatory Integrative Comp Physiol 288, R796-R797
   Full Text »    PDF »
A Strong Nerve Dependence of Sonic hedgehog Expression in Basal Cells in Mouse Taste Bud and an Autonomous Transcriptional Control of Genes in Differentiated Taste Cells.
H. Miura, H. Kato, Y. Kusakabe, M. Tagami, J. Miura-Ohnuma, Y. Ninomiya, and A. Hino (2004)
Chem Senses 29, 823-831
   Abstract »    Full Text »    PDF »
Umami Taste Responses Are Mediated by {alpha}-Transducin and {alpha}-Gustducin.
W. He, K. Yasumatsu, V. Varadarajan, A. Yamada, J. Lem, Y. Ninomiya, R. F. Margolskee, and S. Damak (2004)
J. Neurosci. 24, 7674-7680
   Abstract »    Full Text »    PDF »
Automatically Parcellating the Human Cerebral Cortex.
B. Fischl, A. van der Kouwe, C. Destrieux, E. Halgren, F. Segonne, D. H. Salat, E. Busa, L. J. Seidman, J. Goldstein, D. Kennedy, et al. (2004)
Cereb Cortex 14, 11-22
   Abstract »    Full Text »    PDF »
Electrophysiological Heterogeneity in a Functional Subset of Mouse Taste Cells during Postnatal Development.
V. Ghiaroni, F. Fieni, P. Pietra, and A. Bigiani (2003)
Chem Senses 28, 827-833
   Abstract »    Full Text »    PDF »
Calcium Signaling Mediated by P2Y Receptors in Mouse Taste Cells.
S. G. Baryshnikov, O. A. Rogachevskaja, and S. S. Kolesnikov (2003)
J Neurophysiol 90, 3283-3294
   Abstract »    Full Text »    PDF »
Enhanced Responses of the Chorda Tympani Nerve to Sugars in the Ventromedial Hypothalamic Obese Rat.
Y. Shimizu, M. Yamazaki, K. Nakanishi, M. Sakurai, A. Sanada, T. Takewaki, and K. Tonosaki (2003)
J Neurophysiol 90, 128-133
   Abstract »    Full Text »    PDF »
Neuropeptides modulate rat chorda tympani responses.
S. A. Simon, L. Liu, and R. P. Erickson (2003)
Am J Physiol Regulatory Integrative Comp Physiol 284, R1494-R1505
   Abstract »    Full Text »    PDF »
Recovery of Amiloride-Sensitive Neural Coding during Regeneration of the Gustatory Nerve: Behavioral-Neural Correlation of Salt Taste Discrimination.
K. Yasumatsu, H. Katsukawa, K. Sasamoto, and Y. Ninomiya (2003)
J. Neurosci. 23, 4362-4368
   Abstract »    Full Text »    PDF »
Expression and Physiological Actions of Cholecystokinin in Rat Taste Receptor Cells.
S. Herness, F.-l. Zhao, S.-g. Lu, N. Kaya, and T. Shen (2002)
J. Neurosci. 22, 10018-10029
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882