Behavioral palatability of dietary fatty acids correlates with the intracellular calcium ion levels induced by the fatty acids in GPR120-expressing cells

We recently reported that G-protein-coupled receptor 120 (GPR120) is expressed on taste buds, and that rodents showed preference for long-chain fatty acids (LCFA) at a low concentration. We also showed that the LCFA (1% linoleic acid) increased the extracellular dopamine (DA) level in the nucleus accumbens (NAc), which participates in reward behavior. However, the mechanism underlying the involvement of the GPR120-agonistic activity of LCFA in the palatability of dietary fat remains elusive. Therefore, we examined the association between the GPR120-agonistic activity and palatability of LCFA. First, we measured Ca2+ signaling in HEK293 cells stably expressing GPR120 under stimulation by various LCFAs. We then assessed the palatability of the various LCFAs by testing the licking behavior in mice and measured the changes in the NAc-DA level by in vivo microdialysis. Consequently, 14- to 22-carbon unsaturated LCFAs showed strong GPR120-agonistic activity. Additionally, mice displayed high licking response to unsaturated 16- and 18-carbon LCFAs, and unsaturated 18-carbon LCFA significantly increased the DA level. The licking rate and the LCFA-dependent increase in DA level also correlated well with the GPR120-agonistic activity. These findings demonstrate that chemoreception of LCFA by GPR120 is involved in the recognition and palatability of dietary fat.