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ERK1/2 activation in human taste bud cells regulates fatty acid signaling and gustatory perception of fat in mice and humans
Author(s) -
Subramaniam Selvakumar,
Ozdener Mehmet Hakan,
AbdoulAzize Souleymane,
Saito Katsuyoshi,
Malik Bilal,
Maquart Guillaume,
Hashimoto Toshihiro,
Marambaud Philippe,
Aribi Mourad,
Tordoff Michael G.,
Besnard Philippe,
Khan Naim Akhtar
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201600422r
Subject(s) - small interfering rna , linoleic acid , cd36 , gpr120 , kinase , signal transduction , gene knockdown , microbiology and biotechnology , endocrinology , medicine , biology , taste bud , free fatty acid receptor , taste , fatty acid , polyunsaturated fatty acid , transfection , receptor , biochemistry , g protein coupled receptor , gene
Obesity is a major public health problem. An in‐depth knowledge of the molecular mechanisms of orosensory 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‐ERK1/2ETS‐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 Ca 2+ signaling via opening of the calcium‐homeostasis modulator‐1 (CALHM1) channel. Furthermore, fatty acid–evoked Ca 2+ 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 Ca 2+ 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. FASEBJ. 30, 3489–3500 (2016). www.fasebj.org