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

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 behavioral, 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 effects of their blocking activation of endogenous leptin and endocannabinoid signaling 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, LA effect was gradually decreased and 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 signaling, possibly due to increased production of endocannabinoids in taste tissue. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.