title: ERK1/2 activation in human taste bud cells regulates fatty acid signaling and gustatory perception of fat in mice and humans.
abstract: 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.
authors.affiliation: Unité Mixte de Recherche U866, INSERM, Université de Bourgogne, AgroSup, Dijon, France.
authors.forename: Selvakumar
authors.initials: S
authors.lastname: Subramaniam
authors.affiliation: Monell Chemical Senses Center, Philadelphia, Pennsylvania, USA.
authors.forename: Mehmet Hakan
authors.initials: MH
authors.lastname: Ozdener
authors.affiliation: Unité Mixte de Recherche U866, INSERM, Université de Bourgogne, AgroSup, Dijon, France.
authors.forename: Souleymane
authors.initials: S
authors.lastname: Abdoul-Azize
authors.affiliation: Kao Corporation, Tokyo, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Saito
authors.affiliation: Monell Chemical Senses Center, Philadelphia, Pennsylvania, USA.
authors.forename: Bilal
authors.initials: B
authors.lastname: Malik
authors.affiliation: Unité Mixte de Recherche U866, INSERM, Université de Bourgogne, AgroSup, Dijon, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Maquart
authors.affiliation: Tokushima Bunri University, Tokushima, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Hashimoto
authors.affiliation: Litwin-Zucker Research Center for the Study of Alzheimer's Disease, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
authors.forename: Philippe
authors.initials: P
authors.lastname: Marambaud
authors.affiliation: Laboratory of Applied Molecular Biology and Immunology, Abou Bekr Bel-Kaid University, Tlemcen, Algeria.
authors.forename: Mourad
authors.initials: M
authors.lastname: Aribi
authors.affiliation: Monell Chemical Senses Center, Philadelphia, Pennsylvania, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Tordoff
authors.affiliation: Unité Mixte de Recherche U866, INSERM, Université de Bourgogne, AgroSup, Dijon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Besnard
authors.affiliation: Unité Mixte de Recherche U866, INSERM, Université de Bourgogne, AgroSup, Dijon, France; naim.khan@u-bourgogne.fr.
authors.forename: Naim Akhtar
authors.initials: NA
authors.lastname: Khan
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D004041:Dietary Fats / Q000378:metabolism; D004159:Diphenylamine / Q000031:analogs & derivatives / Q000494:pharmacology; D005227:Fatty Acids / Q000235:genetics* / Q000378:metabolism; D005518:Food Preferences / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics; D009765:Obesity / Q000378:metabolism; D013649:Taste / Q000187:drug effects* / Q000502:physiology; D013650:Taste Buds / Q000187:drug effects*; D055697:Taste Perception / Q000187:drug effects / Q000235:genetics
chemical_list: D001549:Benzamides; D004041:Dietary Fats; D005227:Fatty Acids; D035683:MicroRNAs; C506614:mirdametinib; D004159:Diphenylamine
keywords: CALHM1; MAPK; lipids