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FASEB J. 2016 Oct;30(10):3489-3500. Epub 2016 Jun 29.

ERK1/2 activation in human taste bud cells regulates fatty acid signaling and gustatory perception of fat in mice and humans.

Author information

1
Unité Mixte de Recherche U866, INSERM, Université de Bourgogne, AgroSup, Dijon, France.
2
Monell Chemical Senses Center, Philadelphia, Pennsylvania, USA.
3
Kao Corporation, Tokyo, Japan.
4
Tokushima Bunri University, Tokushima, Japan.
5
Litwin-Zucker Research Center for the Study of Alzheimer's Disease, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
6
Laboratory of Applied Molecular Biology and Immunology, Abou Bekr Bel-Kaid University, Tlemcen, Algeria.
7
Unité Mixte de Recherche U866, INSERM, Université de Bourgogne, AgroSup, Dijon, France; naim.khan@u-bourgogne.fr.

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.

KEYWORDS:

CALHM1; MAPK; lipids

PMID:
27358389
PMCID:
PMC5024696
DOI:
10.1096/fj.201600422R
[Indexed for MEDLINE]
Free PMC Article

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