CD36- and GPR120-Mediated Ca2+ Signaling in Human Taste Bud Cells Mediates Differential Responses to Fatty Acids and Is Altered in Obese Mice

Abstract

Background & Aims It is important to increase our understanding of gustatory detection of dietary fat and its contribution to fat preference. We studied the roles of the fat taste receptors CD36 and GPR120 and their interactions via Ca2+ signaling in fungiform taste bud cells (TBC). Methods We measured Ca2+ signaling in human TBC, transfected with small interfering RNAs (siRNAs) against mRNAs encoding CD36 and GPR120 (or control siRNAs). We also studied Ca2+ signaling in TBC from CD36−/− mice and from wild-type lean and obese mice. Additional studies were conducted with mouse enteroendocrine cell line STC-1 that express GPR120 and stably transfected with human CD36. We measured release of serotonin and GLP-1 from human and mice TBC in response to CD36 and GPR120 activation. Results High concentrations of linoleic acid induced Ca2+ signaling via CD36 and GPR120 in human and mice TBC as well as in STC-1 cells, whereas low concentrations induced Ca2+ signaling via only CD36. Incubation of human and mice fungiform TBC with lineoleic acid downregulated CD36 and upregulated GPR120 in membrane lipid rafts. Obese mice had decreased spontaneous preference for fat. Fungiform TBC from obese mice had reduced Ca2+ and serotonin responses but increased release of GLP1, along with reduced levels of CD36 and increased levels of GPR120 in lipid rafts. Conclusions CD36 and GPR120 have non-overlapping roles in TBC signaling during oro-gustatory perception of dietary lipids; these are differentially regulated by obesity.

The oral lipid sensor GPR120 is not indispensable for the orosensory detection of dietary lipids in mice

“…In contrast, GPR120 was systematically detected in murine and human gustatory papillae ( 11,15,18 ) in which it was frequently coexpressed with CD36 ( 11,19 ). This last observation raises the question of the respective role(s) of these two LCFA receptors in the coding mechanisms eliciting the oro-sensory detection of dietary lipids at the periphery.…”

“…This last observation raises the question of the respective role(s) of these two LCFA receptors in the coding mechanisms eliciting the oro-sensory detection of dietary lipids at the periphery. Recently, it was shown that CD36 and GPR120 have non-overlapping roles in the LCFA-mediated signaling in human TBCs ( 19 ). Whether GPR120 plays a primary role in oral fat detection and preference remains a subject of debate.…”

Oral Fatty Acid Sensitivity among Obesity Resistant and Obesity Susceptible Individuals

“…There appears to be inter-individual variability with reported magnitudes of four-to forty-fold for the detection of free fatty acids among adults and children [4,13]. A number of mechanisms underlying oral fat detection have been purported, with the glycoprotein, CD36 appearing to play a key role as a prime fatty acid taste receptor, especially when concentrations are low [14]. Several researchers have shown fat sensitive people have a lower preference to high fat foods or have a lower fat intake [3,4,15].…”

Perception oro-sensorielle des lipides alimentaires et obésité

“…En effet, on observe une réduction de la réponse calcique déclenchée par les lipides au niveau de cellules gustatives fraîchement isolées (Chevrot et al, 2013). Ce phéno-mène n'est pas la conséquence d'une chute de l'expression du lipido-récepteur CD36 dans ces cellules (Chevrot et al, 2013), mais d'une perturbation de son transfert dans les radeaux lipidiques limitant ainsi la transduction du signal lipidique au niveau des cellules réceptrices gustatives (Ozdener et al, 2014). La conséquence de ce changement est une moindre sécré-tion de sérotonine (Ozdener et al, 2014).…”

“…Ce phéno-mène n'est pas la conséquence d'une chute de l'expression du lipido-récepteur CD36 dans ces cellules (Chevrot et al, 2013), mais d'une perturbation de son transfert dans les radeaux lipidiques limitant ainsi la transduction du signal lipidique au niveau des cellules réceptrices gustatives (Ozdener et al, 2014). La conséquence de ce changement est une moindre sécré-tion de sérotonine (Ozdener et al, 2014). Puisque ce neuromédiateur semble être impliqué dans le transfert du signal gustatif, cet événement pourrait à lui seul expliquer la réduction la sensibilité oro-sensorielle pour les lipides alimentaires observée chez les souris obèses.…”