Modulation of sweet taste sensitivities by endogenous leptin and endocannabinoids in mice.
CONCLUSIONS
Potential roles of endogenous leptin and endocannabinoids in sweet taste were examined by using pharmacological antagonists and mouse models including leptin receptor deficient (db/db) and diet-induced obese (DIO) mice. Chorda tympani (CT) nerve responses of lean mice to sweet compounds were increased after administration of leptin antagonist (LA) but not affected by administration of cannabinoid receptor antagonist (AM251). db/db mice showed clear suppression of CT responses to sweet compounds after AM251, increased endocannabinoid levels in the taste organ, and enhanced expression of a biosynthesizing enzyme of endocannabinoids in taste cells. The effect of LA was gradually decreased and that of AM251 was increased during the course of obesity in DIO mice. These findings suggest that circulating leptin, but not local endocannabinoids, is a dominant modulator for sweet taste in lean mice and endocannabinoids become more effective modulators of sweet taste under conditions of deficient leptin signalling.
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.
Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University, Fukuoka, 812-8582, Japan.
Mayu
M
Niki
Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University, Fukuoka, 812-8582, Japan.
Masafumi
M
Jyotaki
Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University, Fukuoka, 812-8582, Japan.
Ryusuke
R
Yoshida
Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University, Fukuoka, 812-8582, Japan.|Division of Sensory Physiology, Research and Development Center for Taste and Odor Sensing, Kyushu University, Fukuoka, Japan.
Keiko
K
Yasumatsu
Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University, Fukuoka, 812-8582, Japan.
Noriatsu
N
Shigemura
Department of Anatomy and Neurobiology, University of California, Irvine, School of Medicine, Irvine, CA, USA.|Division of Biomedical Sciences, University of California, Riverside, School of Medicine, Riverside, CA, USA.
Nicholas V
NV
DiPatrizio
Department of Anatomy and Neurobiology, University of California, Irvine, School of Medicine, Irvine, CA, USA.|Department of Pharmacology, University of California, Irvine, School of Medicine, Irvine, CA, USA.|Department of Biological Chemistry, University of California, Irvine, School of Medicine, Irvine, CA, USA.|Unit of Drug Discovery and Development, Italian Institute of Technology, Genoa, Italy.
Daniele
D
Piomelli
Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University, Fukuoka, 812-8582, Japan.|Division of Sensory Physiology, Research and Development Center for Taste and Odor Sensing, Kyushu University, Fukuoka, Japan.
Yuzo
Y
Ninomiya
D000818:Animals; D001095:Arachidonic Acids / Q000502:physiology; D002814:Chorda Tympani Nerve / Q000502:physiology; D063388:Endocannabinoids / Q000502:physiology*; D005260:Female; D005989:Glycerides / Q000502:physiology; D020738:Leptin / Q000097:blood / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000503:physiopathology*; D013649:Taste / Q000502:physiology*; D013650:Taste Buds / Q000502:physiology
D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; D020738:Leptin; C094503:glyceryl 2-arachidonate