GPR84 Is Essential for the Taste of Medium Chain Saturated Fatty Acids

The ability of mammalian taste cells to respond to fatty acids (FAs) has garnered significant attention of late and has been proposed to represent a sixth primary taste. With few exceptions, studies on FA taste have centered exclusively on polyunsaturated FAs, most notably on linoleic acid. In the current study, we have identified an additional FA receptor, GPR84, in the gustatory system that responds to the medium chains saturated FAs (MCFAs) in male mice. GPR84 ligands activate both Type II and Type III taste cells in calcium imaging and patch clamp recording assays. MCFAs depolarize and lead to a rise in intracellular free [Ca2+] in mouse taste cells in a concentration-dependent fashion and the relative ligand specificity in taste cells is consistent with the response profile of GPR84 expressed in a heterologous system. A systemic Gpr84-/- mouse model reveals a specific deficit in both the neural (via chorda tympani recording) and behavioral responses to administration of oral MCFAs compared to wild type mice. Together, we show that the peripheral taste system can respond to an additional class of FAs, the saturated FAs, and that the cognate receptor necessary for this ability is GPR84. Significance Statement Recognition of fatty acids by taste receptor cells in the oral cavity has been suggested to underlie the taste cue for dietary fat. In vitro and in vivo studies in both animal models and humans supports the notion fat may represent an additional taste primer. However, virtually all these studies have focused on the ability of polyunsaturated fatty acids, like linoleic acid, to activate taste pathways. We have identified GPR84 in the taste system that underlies the ability of mice to recognize and respond to medium chain saturated fatty acids. The ability to sense the taste of saturated fats may be important for controlling the intake of this class of fats whose intake is a greater concern for human health.