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

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2527-2545
Number of pages19
JournalJournal of Physiology
Volume593
Issue number11
DOIs
Publication statusPublished - Jun 1 2015

Fingerprint

Endocannabinoids
Leptin
Obese Mice
Chorda Tympani Nerve
Diet
Leptin Receptors
Cannabinoid Receptor CB1
Lipoprotein Lipase
Prosencephalon
Hypothalamus
Brain Stem
Obesity
Eating
Pharmacology

All Science Journal Classification (ASJC) codes

  • Physiology

Cite this

Niki, M., Jyotaki, M., Yoshida, R., Yasumatsu, K., Shigemura, N., DiPatrizio, N. V., ... Ninomiya, Y. (2015). Modulation of sweet taste sensitivities by endogenous leptin and endocannabinoids in mice. Journal of Physiology, 593(11), 2527-2545. https://doi.org/10.1113/JP270295

Modulation of sweet taste sensitivities by endogenous leptin and endocannabinoids in mice. / Niki, Mayu; Jyotaki, Masafumi; Yoshida, Ryusuke; Yasumatsu, Keiko; Shigemura, Noriatsu; DiPatrizio, Nicholas V.; Piomelli, Daniele; Ninomiya, Yuzo.

In: Journal of Physiology, Vol. 593, No. 11, 01.06.2015, p. 2527-2545.

Research output: Contribution to journalArticle

Niki, M, Jyotaki, M, Yoshida, R, Yasumatsu, K, Shigemura, N, DiPatrizio, NV, Piomelli, D & Ninomiya, Y 2015, 'Modulation of sweet taste sensitivities by endogenous leptin and endocannabinoids in mice', Journal of Physiology, vol. 593, no. 11, pp. 2527-2545. https://doi.org/10.1113/JP270295
Niki, Mayu ; Jyotaki, Masafumi ; Yoshida, Ryusuke ; Yasumatsu, Keiko ; Shigemura, Noriatsu ; DiPatrizio, Nicholas V. ; Piomelli, Daniele ; Ninomiya, Yuzo. / Modulation of sweet taste sensitivities by endogenous leptin and endocannabinoids in mice. In: Journal of Physiology. 2015 ; Vol. 593, No. 11. pp. 2527-2545.
@article{5c07aa1e0cfb46e58b5589ca6ff0dd14,
title = "Modulation of sweet taste sensitivities by endogenous leptin and endocannabinoids in mice",
abstract = "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.",
author = "Mayu Niki and Masafumi Jyotaki and Ryusuke Yoshida and Keiko Yasumatsu and Noriatsu Shigemura and DiPatrizio, {Nicholas V.} and Daniele Piomelli and Yuzo Ninomiya",
year = "2015",
month = "6",
day = "1",
doi = "10.1113/JP270295",
language = "English",
volume = "593",
pages = "2527--2545",
journal = "Journal of Physiology",
issn = "0022-3751",
publisher = "Wiley-Blackwell",
number = "11",

}

TY - JOUR

T1 - Modulation of sweet taste sensitivities by endogenous leptin and endocannabinoids in mice

AU - Niki, Mayu

AU - Jyotaki, Masafumi

AU - Yoshida, Ryusuke

AU - Yasumatsu, Keiko

AU - Shigemura, Noriatsu

AU - DiPatrizio, Nicholas V.

AU - Piomelli, Daniele

AU - Ninomiya, Yuzo

PY - 2015/6/1

Y1 - 2015/6/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84929964108&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929964108&partnerID=8YFLogxK

U2 - 10.1113/JP270295

DO - 10.1113/JP270295

M3 - Article

C2 - 25728242

AN - SCOPUS:84929964108

VL - 593

SP - 2527

EP - 2545

JO - Journal of Physiology

JF - Journal of Physiology

SN - 0022-3751

IS - 11

ER -