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Leptin Modulates Behavioral Responses to Sweet Substances by Influencing Peripheral Taste Structures

Section of Oral Neuroscience (N.S., R.O., Y.N.) and Section of Removable Prosthesis (R.O., K.K.), Graduate School of Dental Sciences, Kyushu University, Fukuoka, 812-8582, Japan; National Food Research Institute (Y.K., H.M., A.H.), Ibaraki 305-8642, Japan; Bio-oriented Technology Research Advancement Institution (A.H., Y.N.), Tokyo 105, Japan; and Department of Chemistry (K.N.), Asahi University School of Dentistry, Gifu 501-0296, Japan

Address all correspondence and requests for reprints to: Yuzo Ninomiya, Section of Oral Neuroscience, Graduate School of Dental Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. E-mail: nino{at}dent.kyushu-u.ac.jp.

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.

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