title: Activation of tongue-expressed GPR40 and GPR120 by non caloric agonists is not sufficient to drive preference in mice.
abstract: There is mounting evidence that, in addition to texture and olfaction, taste plays a role in the detection of long chain fatty acids. Triglycerides, the main components of oils and dietary fat, are hydrolyzed in the mouth by a lingual lipase secreted from the von Ebner gland and the released free fatty acids are detected by the taste system. GPR40 and GPR120, two fatty acid responsive G-protein-coupled receptors (GPCRs), are expressed in taste bud cells, and knockout mice lacking either of those receptors have blunted taste nerve responses to and reduced preference for fatty acids. Here we investigated whether activation of those GPCRs is sufficient to elicit fat taste and preference. Five non-fatty acid agonists of GPR40 and two non-fatty acid agonists of GPR120 activated the glossopharyngeal nerve of wild-type mice but not of knockout mice lacking the cognate receptor. In human subjects, two-alternative forced choice (2-AFC) tests, triangle tests and sensory profiling showed that non fatty acid agonists of GPR40 dissolved in water are detected in sip and spit tests and elicit a taste similar to that of linoleic acid, whereas 2-AFC tests showed that two agonists of GPR120 in water are not perceived fattier than water alone. Wild-type mice did not show any preference for five agonists of GPR40, two agonists of GPR120 and mixtures of both agonists over water in two-bottle preference tests. Together these data indicate that GPR40 mediated taste perception is not sufficient to generate preference.
authors.affiliation: Nestlé Research Center, Vers-chez-les-Blanc, Lausanne 1000, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Godinot
authors.forename: K
authors.initials: K
authors.lastname: Yasumatsu
authors.forename: M E
authors.initials: ME
authors.lastname: Barcos
authors.forename: N
authors.initials: N
authors.lastname: Pineau
authors.forename: M
authors.initials: M
authors.lastname: Ledda
authors.forename: F
authors.initials: F
authors.lastname: Viton
authors.forename: Y
authors.initials: Y
authors.lastname: Ninomiya
authors.forename: J
authors.initials: J
authors.lastname: le Coutre
authors.forename: S
authors.initials: S
authors.lastname: Damak
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D005227:Fatty Acids / Q000494:pharmacology; D005260:Female; D005518:Food Preferences / Q000502:physiology*; D006801:Humans; D019787:Linoleic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000096:biosynthesis / Q000378:metabolism*; D000077154:Rosiglitazone; D013649:Taste / Q000502:physiology*; D045162:Thiazolidinediones / Q000494:pharmacology; D014059:Tongue / Q000378:metabolism*; D055815:Young Adult
chemical_list: C498007:FFAR4 protein, mouse; D005227:Fatty Acids; C473036:Ffar1 protein, mouse; D043562:Receptors, G-Protein-Coupled; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D019787:Linoleic Acid; D002118:Calcium
keywords: 2-AFC; DMSO; G-protein-coupled receptors; GL; GPCRs; GPR40; KO; dimethyl sulfoxide; fat; glossopharyngeal; knockout; mouse; psychophysics; taste; two-alternative forced choice