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PNAS 97 (20): 11044-11049

Copyright © 2000 by the National Academy of Sciences.


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}

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

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

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »

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