Recent findings challenge this limited viewpoint, strongly suggesting that the sense of taste also plays a significant role in dietary lipid perception and might therefore be involved in the preference for fatty foods and, consequently, in the obesity risk. Compelling evidences implicate the multifunctional protein CD36 as a gustatory lipid sensor. This receptor-like glycoprotein, which belongs to the scavenger receptor family, binds saturated and unsaturated long-chain fatty acids with an affinity in the nanomolar range. CD36 is found in rodent lingual epithelium in which it is strictly restricted to some taste bud cells. CD36 gene inactivation AZ 960 905586-69-8 abolishes spontaneous fat preference and the cephalic phase of digestion triggered by a LCFA deposition onto the tongue in the mouse. These physiological effects take place through the gustatory circuitry. Indeed, the spontaneous preference for or, conversely, the conditioned aversion to LCFA require intact gustatory nerves. Moreover, neuronal activation in the gustatory area of the nucleus of the solitary tract elicited by a lingual deposition of LCFA in wild-type mice cannot be reproduced in CD36-null animals. Finally, LCFA selectively trigger a rapid and huge increase in i in CD36-positive TBC isolated from mouse circumvallate papillae. This change, initiated by the phosphorylation of Src protein tyrosine kinases, leads to the release of neurotransmitters which activates the gustatory afferent nerve fibers. Altogether these data strongly highlight the crucial role played by CD36 in the oro-sensory perception of dietary lipids in the mouse. This last finding seems paradoxical since CD36 does not belong to the G protein-coupled receptor family whereas most of the other taste receptors, such as T1Rs and T2Rs responsible for sweet, umami and bitter tastes, do. It has been recently reported that two members of the GPCR family displaying specificity for LCFA also play a role in the taste for fat. GPR40 and GPR120 are specifically expressed in the gustatory epithelium of the tongue in the mouse. Knock-out mice lacking GPR40 or GPR120 have diminished preference for oleic acid and linoleic acid solutions. Contrary to these authors, we have not been able to detect GPR40 mRNA in mouse CVP, similarly to Matsumura and colleagues in the rat. Origin of this discrepancy is unclear. By contrast, we confirm the presence of GPR120 in mouse taste buds which raises the question of the respective role played by CD36 and GPR120 in the coding mechanisms for fat taste at the periphery. In this report, expression of genes encoding for CD36 and GPR120 in mouse CVP was explored during the day-night cycle and in mice subjected to nutritional manipulations. Physiological consequences on spontaneous lipid preference were analyzed using behavioural approaches. Many recent studies strongly suggest the existence of a specific gustatory system devoted to the detection of LCFA in rodents and, likely, in humans. Two unrelated lipid-sensor candidates, the multifunctional glycoprotein CD36 and the G protein-coupled receptor GPR120, displaying similar binding specificities for LCFA, have been identified in gustatory papillae in the mouse.