Long-Chain Fatty Acids Inhibit the Human Bitter Taste Receptor TAS2R16 in a Structure-Dependent Manner.

Bitterness limits the development of palatable foods containing bioactive ingredients. This study investigated whether long-chain fatty acids (LCFAs) modulate the human bitter taste receptor TAS2R16 using a HEK293T cell-based calcium assay with salicin as an agonist. None of the tested LCFAs directly activated TAS2R16. Under co-treatment, only oleic acid inhibited salicin-induced calcium responses, shifting the salicin EC50 from 1.82 ± 0.11 mM to 3.55 ± 1.22 mM at 30 μM (p < 0.01). Pretreatment with all LCFAs inhibited TAS2R16 concentration-dependently. Reliable IC50 values were obtained for palmitic acid (8.67 ± 1.44 μM), stearic acid (0.082 ± 0.002 μM), and oleic acid (0.41 ± 0.12 μM), whereas lower plateaus were not reached for myristic, linoleic, and α-linolenic acids. LCFA treatment did not consistently change membrane fluidity, and inhibition was attenuated in the TAS2R16 N96T mutant. These findings demonstrate compound- and treatment-dependent modulation of TAS2R16 by food-derived LCFAs.