Modulation of sweet taste sensitivities by endogenous leptin and endocannabinoids in mice

Mayu Niki, Masafumi Jyotaki, Ryusuke Yoshida, Keiko Yasumatsu, Noriatsu Shigemura, Nicholas V. DiPatrizio, Daniele Piomelli, Yuzo Ninomiya

研究成果: ジャーナルへの寄稿学術誌査読

33 被引用数 (Scopus)


Leptin is an anorexigenic mediator that reduces food intake by acting on hypothalamic receptor Ob-Rb. In contrast, endocannabinoids are orexigenic mediators that act via cannabinoid CB1 receptors in hypothalamus, limbic forebrain, and brainstem. In the peripheral taste system, leptin administration selectively inhibits behavioural, taste nerve and taste cell responses to sweet compounds. Opposing the action of leptin, endocannabinoids enhance sweet taste responses. However, potential roles of endogenous leptin and endocannabinoids in sweet taste remain unclear. Here, we used pharmacological antagonists (Ob-Rb: L39A/D40A/F41A (LA), CB1: AM251) and examined the effects of their blocking activation of endogenous leptin and endocannabinoid signalling on taste responses in lean control, leptin receptor deficient db/db, and diet-induced obese (DIO) mice. Lean mice exhibited significant increases in chorda tympani (CT) nerve responses to sweet compounds after LA administration, while they showed no significant changes in CT responses after AM251. In contrast, db/db mice showed clear suppression of CT responses to sweet compounds after AM251, increased endocannabinoid (2-arachidonoyl-sn-glycerol (2-AG)) levels in the taste organ, and enhanced expression of a biosynthesizing enzyme (diacylglycerol lipase α (DAGLα)) of 2-AG in taste cells. In DIO mice, the LA effect was gradually decreased and the AM251 effect was increased during the course of obesity. Taken together, our results suggest that circulating leptin, but not local endocannabinoids, may be a dominant modulator for sweet taste in lean mice; however, endocannabinoids may become more effective modulators of sweet taste under conditions of deficient leptin signalling, possibly due to increased production of endocannabinoids in taste tissue.

ジャーナルJournal of Physiology
出版ステータス出版済み - 6月 1 2015

!!!All Science Journal Classification (ASJC) codes

  • 生理学


「Modulation of sweet taste sensitivities by endogenous leptin and endocannabinoids in mice」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。