Zizyphin modulates calcium signalling in human taste bud cells and fat taste perception in the mouse

Zizyphin, isolated from Zizyphus sps. leaf extracts, has been shown to modulate sugar taste perception, and the palatability of a sweet solution is increased by the addition of fatty acids. We, therefore, studied whether zizyphin also modulates fat taste perception. Zizyphin was purified from edible fruit of Zizyphus lotus L. Zizyphin-induced increases in [Ca²⁺ ]i in human taste bud cells (hTBC). Zizyphin shared the endoplasmic reticulum Ca²⁺ pool and also recruited, in part, Ca²⁺ from extracellular environment via the opening of store-operated Ca²⁺ channels. Zizyphin exerted additive actions on linoleic acid (LA)-induced increases in [Ca²⁺ ]i in these cells, indicating that zizyphin does not exert its action via fatty acid receptors. However, zizyphin seemed to exert, at least in part, its action via bile acid receptor Takeda-G-protein-receptor-5 in hTBC. In behavioural tests, mice exhibited preference for both LA and zizyphin. Interestingly, zizyphin increased the preference for a solution containing-LA. This study is the first evidence of the modulation of fat taste perception by zizyphin at the cellular level in hTBC. Our study might be helpful for considering the synthesis of zizyphin analogues as 'taste modifiers' with a potential in the management of obesity and lipid-mediated disorders.