Linoleic Acid Induces Calcium Signaling, Src Kinase Phosphorylation, and Neurotransmitter Release in Mouse CD36-positive Gustatory Cells

Abstract

We have recently demonstrated that the cells expressing CD36, localized apically on the taste buds of mouse lingual circumvallate papillae, act as gustatory cells. In the present study we isolated these CD36-positive cells from mouse circumvallate papillae and investigated intracellular signaling events, triggered by a long-chain polyunsaturated fatty acid, i.e. linoleic acid (LA). LA induced increases in free intracellular calcium concentrations, [Ca 2؉ ] i , by recruiting calcium from endoplasmic reticulum pool via inositol 1,4,5-triphosphate production followed by calcium influx via opening of store-operated calcium (SOC) channels. LA also induced phosphorylation of Srcprotein-tyrosine kinases (Src-PTKs), particularly of The tongue contains primarily four types of papillae. Filiforms are involved in the somesthesic perception of foods, whereas fungiforms, foliates, and circumvallates, which contain taste buds, are responsible for the chemosensory perception of basic taste modalities (sweet, bitter, salt, sour, umami (4) demonstrated that the addition of a lipase inhibitor diminished the spontaneous preference for triglycerides. These investigators proposed that the lingual lipase, present in the rodent saliva, might release free fatty acids that would be detected by gustatory cells. The immunolocalization of CD36 in the apical side of few TRC in circumvallate papillae (3) is especially adequate for this function since CD36 is known to exhibit a very high affinity for long-chain fatty acids (5). Consistent with this assumption, we have recently provided the first evidence that CD36-positive gustatory cells play a significant role in dietary lipid perception in the mouse (3). Indeed, the CD36 gene inactivation fully abolished the spontaneous preference for long-chain fatty acids observed in wild-type mice (3). It is noteworthy that this effect on feeding behavior is lipid-specific since sweet preference and bitter aversion are not affected in these transgenic mice (3).To further explore whether a sixth taste modality devoted to the "fat" functionally exists in rodents, the downstream signaling events triggered by the free fatty acid/CD36 interaction in gustatory cells must be studied. We have for the first time purified the CD36-positive gustatory cells from mouse CVP and demonstrated that linoleic acid induced increases in [Ca 2ϩ ] i in these cells via CD36 (6). In the present study we have extended these investigations to characterize the mechanisms of action of linoleic acid on calcium signaling/protein phosphorylation, leading to the release of neurotransmitters, which might be implicated in the activation of afferent nerve fibers.

CD36 Protein Is Involved in Store-operated Calcium Flux, Phospholipase A2 Activation, and Production of Prostaglandin E2

“…In isolated hypothalamic ventromedial nucleus neurons, the addition of oleic acid resulted in alterations of intracellular calcium oscillations, and these effects were reduced by the CD36 inhibitor SSO (67). More evidence for a link between CD36 and cellular calcium was obtained using taste bud cells sorted based on CD36 expression (68). It was shown that exposure of CD36-positive cells to extracellular linoleate increased intracellular calcium through 1,4,5-trisphosphate-mediated release of ER calcium.…”

Taste perception, associated hormonal modulation, and nutrient intake

“…CD36, in particular, seems to play a key role in fatty acid detection. ElYassimi et al 124 showed that linoleic acid binds to mouse gustatory cells that express CD36, triggering the release of noradrenaline and 5-hydroxytryptamine via calcium signaling. The large interindividual variation in the ability to detect oral fatty acids likely affects food intake and weight.…”

STIM1, CD36 lingual et perception gustative lipidique

“…De plus, nous avons démontré chez la souris que, en réponse à l'interaction entre les AGLC et le CD36 au niveau des TRC, le CD36 est couplé à la phosphorylation de tyrosines kinases de la famille Src (Fyn-p 59 et Yes-p 62 ) [7]. Nous avons constaté que les AGLC induisent également une augmentation de la concentration de Ca 2+ intracellulaire ([Ca 2+ ]i) dans les TRC [8].…”

“…Ce phénomène est strictement dépendant de CD36 car la signalisation calcique est fortement réduite en présence d'un inhibiteur pharmacologique de la liaison des AGLC à CD36 [8]. Cette augmentation du [Ca 2+ ]i semble résulter d'une mobilisation du calcium du réti-culum endoplasmique (RE) via la production d'inositol triphosphate (IP 3 ) et de l'ouverture des canaux SOC (storeoperated calcium) [7]. Cependant, les mécanismes impliqués dans l'ouverture des canaux SOC des cellules gustatives restaient encore non définis.…”