2001 Fiscal Year Final Research Report Summary
Research in molecular mechanisms of suppression of sweet responses by anti-obesity factor leptin in taste cells.
| Project/Area Number |
12671801
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
SUGIMOTO Kumiko Graduate School, Tokyo Medical and Dental University, Lecturer, 大学院・医歯学総合研究科, 講師 (10133109)
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| Project Period (FY) |
2000 – 2001
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| Keywords | leptin / leptin receptor / taste cell / taste nerve / sweet rasponse / selective suppression / K^+ channel / genetic diabetes |
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| Research Abstract |
Leptin, a hormone released from the adipose tissue, inhibits food intake and increases energy expenditure. We have found a novel function of leptin as a modulator of sweet taste sensitivity in mice. In the lean normal mice, the gustatory nerve responses to sweet stimuli were selectively suppressed depending on plasma leptin level after an intraperitoneal injection of recombinant leptin. Patch-clamp studies using isolated taste cells of lean mice showed that extracellular leptin enhanced K^+ currents of sweet-responsive taste cells, which led to membrane hyperpolarization and a reduction of sweetener-induced depolarization. RT-PCR and in situ hybridization analyzes demonstrated specific expression of mRNA of the long-form functional leptin receptor (Ob-Rb) in taste tissue and cells of lean mice. The genetically diabetic db/db mice, which have defects in Ob-Rb, demonstrated neither a suppression of gustatory neural responses to sweeteners nor an increment of whole-cell K^+ conductance of taste cells even with high doses of leptin. These results suggest that Ob-Rb is specifically expressed in sweet-responsive taste cells of lean mice and that leptin suppresses sweetener-induced depolarization via activation of K^+ channels, leading to a decrease in impulses of sweet-best fibers. It is also suggested that the enhanced sweet responses of db/db mice may result from the lack of inhibitory modulation by leptin.
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