Leptin suppresses sweet taste responses of enteroendocrine STC-1 cells. (22nd September 2016)

• Record Type: Journal Article
• Authors: Jyotaki, Masafumi; Sanematsu, Keisuke; Shigemura, Noriatsu; Yoshida, Ryusuke; Ninomiya, Yuzo
• Is Part Of: Neuroscience. Volume 332(2016)
• Page Start: 76
• Page End: 87
• Publication Date: 2016-09-22
• Subjects: AMPK AMP-activated protein kinase -- CCK Cholecystokinin -- DB denatonium benzoate -- DMEM Dulbecco's modified Eagle's medium -- FBS fetal bovine serum -- Gc glibenclamide -- GIP glucose-dependent insulinotropic peptide -- Glc glucose -- GLP-1 glucagon-like peptide-1 -- GLUT glucose transporters -- Gur gurmarin -- Gα-gust G-protein gustducin -- HBSS Hanks' buffered salt solution -- HEPES 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid -- IP3R3 inositol trisphosphate receptor type 3 -- KATP channel ATP gated K+ channel -- KRB Krebs-Ringer bicarbonate buffer -- LA leptin antagonist, mutant L39A/D40A/F41A -- MSG monosodium glutamate -- Ob-R leptin receptor -- PBS phosphate-buffered saline -- PLC-β2 phospholipase C-β2 -- SC SC45647 -- SGLT1 sodium-glucose tramsporter-1 -- Suc sucrose -- Sucra sucralose -- SUR1 sulfonylurea receptor 1 -- T1R1 or T1R2 or T1R3 taste receptor family 1 member 1 or 2 or 3 -- T2R taste receptor family 2 -- TRPM5 transient receptor potential cation channel, subfamily M, member 5; taste -- incretin -- gut -- calcium imaging; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2016.06.036
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: 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. Abstract: 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 Ca 2+ responses of STC-1 cells to various taste compounds. Ca 2+ 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.