Bitter taste receptors, also known as taste 2 receptors
(T2R),
are expressed throughout the body and are involved in regulating different
physiological processes. T2R expression in the intestinal tract regulates
orexigenic and anorexigenic peptide secretion, thus becoming potential
a potential target for controlling food intake and the prevalence
of obesity and overweight. The present study aims to investigate the
implication of hop bitter compounds such as α-acids, β-acids,
and xanthohumol in the secretion of anorexigenic hormones and T2R
expression in intestinal STC-1 cells. The tested bitter compounds
induced the secretion of the anorexigenic hormones glucagon-like peptide
1 and cholecystokinin concurrently with a selective increase of murine Tas2r expression. Xanthohumol and α-acids selectively
increase Tas2r138 and Tas2r130–Tas2r138 expression, respectively, in STC-1 cells, while
β-acids increased the expression of all bitter receptors studied,
including Tas2r119, Tas2r105, Tas2r138, Tas2r120, and Tas2r130. Increased intracellular calcium levels confirmed this activity.
As all investigated bitter molecules increased Tas2r138 expression, computational studies were performed on Tas2r138 and its human orthologue T2R38 for the first time. Molecular
docking experiments showed that all molecules might be able to bind
both bitter receptors, providing an excellent basis for applying hop
bitter molecules as lead compounds to further design gastrointestinal-permeable
T2R agonists.