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RESEARCH PRODUCT
ERK1/2 activation in human taste bud cells regulates fatty acid signaling and gustatory perception of fat in mice and humans
Bilal MalikSouleymane Abdoul-azizeGuillaume MaquartMourad AribiSelvakumar SubramaniamNaim Akhtar KhanPhilippe MarambaudToshihiro HashimotoMehmet Hakan OzdenerKatsuyoshi SaitoMichael G. TordoffPhilippe Besnardsubject
0301 basic medicineSmall interfering RNAMouseCD36BiochemistryMapkObesechemistry.chemical_compound0302 clinical medicinegpr120Cd36Mice Knockoutchemistry.chemical_classificationGene knockdownbiologyKinaseFatty AcidsTaste PerceptionGPR120Taste BudsLipidsProtein-tyrosine kinases3. Good healthTasteBenzamidesBiotechnologymedicine.medical_specialtyMAP Kinase Signaling SystemLinoleic acid[SDV.BC]Life Sciences [q-bio]/Cellular BiologyPreferenceFood Preferences03 medical and health sciencesCalhm1Internal medicineDietary-fatGeneticsmedicineAnimalsHumans[SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular BiologyCalcium SignalingObesityMolecular Biology[ SDV.BBM ] Life Sciences [q-bio]/Biochemistry Molecular Biology[ SDV.BC ] Life Sciences [q-bio]/Cellular BiologyResearchDiphenylamineFatty acidDietary FatsMicroRNAs030104 developmental biologyEndocrinologychemistrybiology.proteinIon-channelCALHM1Src kinase030217 neurology & neurosurgerydescription
Obesity is a major public health problem. An in-depth knowledge of the molecular mechanisms of oro-sensory detection of dietary lipids may help fight it. Humans and rodents can detect fatty acids via lipido-receptors, such as CD36 and GPR120. We studied the implication of the MAPK pathways, in particular, ERK1/2, in the gustatory detection of fatty acids. Linoleic acid, a dietary fatty acid, induced via CD36 the phosphorylation of MEK1/2-ERK1/2-ETS-like transcription factor-1 cascade, which requires Fyn-Src kinase and lipid rafts in human taste bud cells (TBCs). ERK1/2 cascade was activated by Ca2+ signaling via opening of the calcium-homeostasis modulator-1 (CALHM1) channel. Furthermore, fatty acid–evoked Ca2+ signaling and ERK1/2 phosphorylation were decreased in both human TBCs after small interfering RNA knockdown of CALHM1 channel and in TBCs from Calhm1−/− mice. Targeted knockdown of ERK1/2 by small interfering RNA or PD0325901 (MEK1/2 inhibitor) in the tongue and genetic ablation of Erk1 or Calhm1 genes impaired preference for dietary fat in mice. Lingual inhibition of ERK1/2 in healthy volunteers also decreased orogustatory sensitivity for linoleic acid. Our data demonstrate that ERK1/2-MAPK cascade is regulated by the opening of CALHM1 Ca2+ channel in TBCs to modulate orogustatory detection of dietary lipids in mice and humans.—Subramaniam, S., Ozdener, M. H., Abdoul-Azize, S., Saito, K., Malik, B., Maquart, G., Hashimoto, T., Marambaud, P., Aribi, M., Tordoff, M. G., Besnard, P., Khan, N. A. ERK1/2 activation in human taste bud cells regulates fatty acid signaling and gustatory perception of fat in mice and humans.
year | journal | country | edition | language |
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2016-10-01 |