Leptin suppresses sweet taste responses of enteroendocrine STC-1 cells

- Leptin regulates food intake and energy homeostasis by acting on its receptor expressed in central and peripheral organs.
- We examined the effect of leptin on taste responses and incretin release using mouse enteroendocrine cell line STC-1.
- Leptin selectively reduced the responses to sweet compounds and suppressed sweet-induced GLP-1 secretion from STC-1 cells.
- Leptin's effect on sweet responses of STC-1 cells was inhibited by a leptin antagonist and by KATP channel closer.
- Leptin may regulate the sensing and the absorption of nutrients by modulating sweet sensitivities in the gut.

Leptin is an important hormone that regulates food intake and energy homeostasis by acting on central and peripheral targets. In the gustatory system, leptin is known to selectively suppress sweet responses by inhibiting the activation of sweet sensitive taste cells. Sweet taste receptor (T1R2 + T1R3) is also expressed in gut enteroendocrine cells and contributes to nutrient sensing, hormone release and glucose absorption. Because of the similarities in expression patterns between enteroendocrine and taste receptor cells, we hypothesized that they may also share similar mechanisms used to modify/regulate the sweet responsiveness of these cells by leptin. Here, we used mouse enteroendocrine cell line STC-1 and examined potential effect of leptin on Ca2+ responses of STC-1 cells to various taste compounds. Ca2+ responses to sweet compounds in STC-1 cells were suppressed by a rodent T1R3 inhibitor gurmarin, suggesting the involvement of T1R3-dependent receptors in detection of sweet compounds. Responses to sweet substances were suppressed by ⩾1 ng/ml leptin without affecting responses to bitter, umami and salty compounds. This effect was inhibited by a leptin antagonist (mutant L39A/D40A/F41A) and by ATP gated K+ (KATP) channel closer glibenclamide, suggesting that leptin affects sweet taste responses of enteroendocrine cells via activation of leptin receptor and KATP channel expressed in these cells. Moreover, leptin selectively inhibited sweet-induced but not bitter-induced glucagon-like peptide-1 (GLP-1) secretion from STC-1 cells. These results suggest that leptin modulates sweet taste responses of enteroendocrine cells to regulate nutrient sensing, hormone release and glucose absorption in the gut.