The oral lipid sensor GPR120 is not indispensable for the orosensory detection of dietary lipids in mice

Déborah Ancel,Arnaud Bernard,Selvakumar Subramaniam,Akira Hirasawa,Gozoh Tsujimoto,Toshihiro Hashimoto,Patricia Passilly-Degrace,Naim-Akhtar Khan,Philippe Besnard

doi:10.1194/jlr.m055202

Abstract

Implication of the long-chain fatty acid (LCFA) receptor GPR120, also termed free fatty acid receptor 4, in the taste-guided preference for lipids is a matter of debate. To further unravel the role of GPR120 in the "taste of fat", the present study was conducted on GPR120-null mice and their wild-type littermates. Using a combination of morphological [i.e., immunohistochemical staining of circumvallate papillae (CVP)], behavioral (i.e., two-bottle preference tests, licking tests and conditioned taste aversion) and functional studies [i.e., calcium imaging in freshly isolated taste bud cells (TBCs)], we show that absence of GPR120 in the oral cavity was not associated with changes in i) gross anatomy of CVP, ii) LCFA-mediated increases in intracellular calcium levels ([Ca(2+)]i), iii) preference for oily and LCFA solutions and iv) conditioned avoidance of LCFA solutions. In contrast, the rise in [Ca(2+)]i triggered by grifolic acid, a specific GPR120 agonist, was dramatically curtailed when the GPR120 gene was lacking. Taken together, these data demonstrate that activation of lingual GPR120 and preference for fat are not connected, suggesting that GPR120 expressed in TBCs is not absolutely required for oral fat detection in mice.

Highlights

Implication of the long-chain fatty acid (LCFA) receptor GPR120, termed free fatty acid receptor 4, in the taste-guided preference for lipids is a matter of debate
A LCFA-dependent signaling cascade leading to a huge rise in intracellular calcium levels ([Ca2+]i) was found in mouse CD36-positive taste bud cells (TBCs), associated with neurotransmitter release (8, 9)
GPR120 gene invalidation did not interfere on CD36 and ␣-gustducin expression levels in taste buds as similar mRNA levels were found in circumvallate papilla (CVP) from GPR120+/+ and GPR120Ϫ/Ϫ mice

Summary

Introduction

Implication of the long-chain fatty acid (LCFA) receptor GPR120, termed free fatty acid receptor 4, in the taste-guided preference for lipids is a matter of debate. The rise in [Ca2+]i triggered by grifolic acid, a specific GPR120 agonist, was dramatically curtailed when the GPR120 gene was lacking Taken together, these data demonstrate that activation of lingual GPR120 and preference for fat are not connected, suggesting that GPR120 expressed in TBCs is not absolutely required for oral fat detection in mice.—Ancel, D., A. A growing number of studies strongly suggest that, in addition to textural, olfactory, and post-ingestive cues, the oro-sensory detection of lipids involves a taste component dependent on long-chain fatty acids (LCFAs). There is a tight correlation between CD36 gene expression and oral fat detection sensitivity: CD36 disruption rendered mice unable to properly detect, and prefer, low concentrations of lipids (6, 10, 11). Subjects expressing the A/A alleles at the gene variant rs1761667, which reduces CD36 expression (13), displayed a higher detection threshold (i.e., a lower sensitivity) for lipids than G/G controls (2) and showed a greater attraction for added fats and oils (14)

Methods

Results

Conclusion