Understanding the mechanisms underlying oro-gustatory detection of dietary fat is critical for the prevention and treatment of obesity. The lipid-binding glycoprotein CD36, which is expressed by circumvallate papillae (CVP) of the mouse tongue, has been implicated in oro-gustatory perception of dietary lipids. Here, we demonstrate that stromal interaction molecule 1 (STIM1), a sensor of Ca 2+ depletion in the endoplasmic reticulum, mediates fatty acid-induced Ca 2+ signaling in the mouse tongue and fat preference. We showed that linoleic acid (LA) induced the production of arachidonic acid (AA) and lysophosphatidylcholine (Lyso-PC) by activating multiple phospholipase A 2 isoforms via CD36. This activation triggered Ca 2+ influx in CD36-positive taste bud cells (TBCs) purified from mouse CVP. LA also induced the production of Ca 2+ influx factor (CIF). STIM1 was found to regulate LA-induced CIF production and the opening of multiple store-operated Ca 2+ (SOC) channels. Furthermore, CD36-positive TBCs from Stim1 -/-mice failed to release serotonin, and Stim1 -/-mice lost the spontaneous preference for fat that was observed in wild-type animals. Our results suggest that fatty acid-induced Ca 2+ signaling, regulated by STIM1 via CD36, might be implicated in oro-gustatory perception of dietary lipids and the spontaneous preference for fat. IntroductionThe sense of taste informs the organism about the quality of ingested food. Five basic taste modalities, e.g., sweet, sour, bitter, salty, and umami, have so far been identified (1). Recent compelling evidence from rodents raises the possibility of an additional sixth taste modality devoted to the perception of lipids (2-4) that are released by the action of lingual lipases, present in the salivary secretions (5). Fukuwatari et al. (6) and Laugerette et al. (2) have documented the expression of the receptor-like lipid-binding protein CD36 in rat and mouse circumvallate papillae (CVP), respectively. Laugerette et al. (2) have provided the first evidence for the involvement of lingual CD36 in dietary lipid perception in the mouse. Indeed, Cd36 gene inactivation completely abolished the spontaneous preference for long-chain fatty acids (LCFAs) observed in wild-type mice. This effect is lipid specific, since the preference for sweet and aversion to bitterness reported in controls were not altered in Cd36-null mice. These observations regarding the implication of CD36 in the perception of lipid taste have also been confirmed by other investigators (7).The coupling of CD36 cell signaling to a downstream second messenger cascade has been explored in mouse taste bud cells (TBCs) (3,8). The experiments conducted on CD36-positive TBCs purified from mouse CVP demonstrated that linoleic acid (LA), an LCFA, induced increases in free intracellular calcium concentrations, [Ca 2+ ] i by binding to CD36 (3). We have reported that LCFAs induced the production of inositol-1,4,5-trisphosphate (IP 3 ) and, consequently, recruited Ca 2+ from the endoplasmic reticulum, followed by Ca 2+ inf...

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Submaxillary gland extracts have been fractionated to characterize the enzyme responsible for the T‐kininogenase activity previously reported in this tissue [Damas, J. & Adam, A. (1985) Mol. Physiol 8, 307–316] and to know whether this activity could be of physiological relevance, since no enzyme reacting in catalytic amounts has been described so far to be able to release a vasoactive peptide from T‐kininogen.The purified enzyme, provisionally called endopeptidase K, has an apparent Mr of 27000 when not reduced prior to analysis but 21000 after reduction and an acidic pI of 4.3 ± 0.1. Antigenically, it is not related to tissue kallikrein. Upon incubation with purified T‐kininogen it may induce a complete liberation of T‐kinin from the precursor provided it is added in stoichiometric amounts. However, in parallel with the liberation of immunoreactive kinin, a proteolysis of T‐kininogen is observed which is not restricted to the site of insertion of T‐kinin as would be expected using a specific kininogenase.In agreement with these results, no change of the mean blood pressure was observed upon injection of endopeptidase K into the circulation of normal rats even if the amount of injected enzyme was up to ten times that required for tissue kallikrein to induce a significant fall in blood pressure.However, in spite of the large proteolysis induced by incubation with stoichiometric amounts of endopeptidase K, the total papain inhibiting capacity of T‐kininogen as well as the value of the apparent inhibition constant, Ki, with this proteinase remained unchanged. Proteolytic fragments which retain cysteine‐proteinase‐inhibiting activity may therefore be released from T‐kininogen by endopeptidase K more easily than immunoreactive kinin, thus emphasizing a prominent function of proteinase inhibitor or of proteinase inhibitor precursor for this molecule.

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It has been well propounded that there exists five basic taste modalities, e.g., sweet, sour, bitter, salty and umami. Recent compelling evidence from rodents and human beings raises the possibility for an additional sixth taste modality devoted to the perception of lipids. A number of studies have suggested that lingual CD36, a glycoprotein, mainly expressed by circumvallate papillae of the tongue, might be implicated in the perception of dietary fat taste. G protein-coupled receptors (GPCRs) are important signaling molecules for many aspects of cellular function. It has been recently shown that these receptors particularly GPR40 and GPR120 might also be involved in lipid taste perception. In this article, we highlight the cell activation mechanisms, responsible for the downstream cell signaling which might help understand the lipid-mediated regulation of feeding behavior, critically involved in the development of several diseases like obesity and other metabolic disorders. We also raise the question whether lipid gustatory cells can be the target of anti-obesity strategies.