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 orosensory detection of dietary lipids may help fight it. Humans and rodents can detect fatty acids via lipido-receptors, such as CD36 andGPR120.We studied the implication of theMAPK 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 interferingRNAor PD0325901 (MEK1/2 inhibitor) in the tongue and genetic ablation of Erk1 orCalhm1 genes impairedpreference for dietaryfat inmice.Lingual inhibition ofERK1/2in healthy volunteers also decreased orogustatory sensitivity for linoleic acid. Our data demonstrate that ERK1/2-MAPKcascade 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.ERK1/2activationinhumantastebudcells regulates fatty acidsignalingandgustatory perception of fat inmice andhumans.