1932

Abstract

The gastrointestinal tract represents the largest interface between the human body and the external environment. It must continuously monitor and discriminate between nutrients that need to be assimilated and harmful substances that need to be expelled. The different cells of the gut epithelium are therefore equipped with a subtle chemosensory system that communicates the sensory information to several effector systems involved in the regulation of appetite, immune responses, and gastrointestinal motility. Disturbances or adaptations in the communication of this sensory information may contribute to the development or maintenance of disease. This is a new emerging research field in which perception of taste can be considered as a novel key player participating in the regulation of gut function. Specific diets or agonists that target these chemosensory signaling pathways may be considered as new therapeutic targets to tune adequate physiological processes in the gut in health and disease.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-physiol-021317-121332
2018-02-10
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/physiol/80/1/annurev-physiol-021317-121332.html?itemId=/content/journals/10.1146/annurev-physiol-021317-121332&mimeType=html&fmt=ahah

Literature Cited

  1. Chaudhari N, Roper SD. 1.  2010. The cell biology of taste. J. Cell Biol. 190:285–96 [Google Scholar]
  2. Depoortere I.2.  2014. Taste receptors of the gut: emerging roles in health and disease. Gut 63:179–90 [Google Scholar]
  3. Daniel H, Zietek T. 3.  2015. Taste and move: glucose and peptide transporters in the gastrointestinal tract. Exp. Physiol. 100:1441–50 [Google Scholar]
  4. Röder PV, Geillinger KE, Zietek TS, Thorens B, Koepsell H, Daniel H. 4.  2014. The role of SGLT1 and GLUT2 in intestinal glucose transport and sensing. PLOS ONE 9:e89977 [Google Scholar]
  5. Stümpel F, Burcelin R, Jungermann K, Thorens B. 5.  2001. Normal kinetics of intestinal glucose absorption in the absence of GLUT2: evidence for a transport pathway requiring glucose phosphorylation and transfer into the endoplasmic reticulum. PNAS 98:11330–35 [Google Scholar]
  6. Kellett GL, Helliwell PA. 6.  2000. The diffusive component of intestinal glucose absorption is mediated by the glucose-induced recruitment of GLUT2 to the brush-border membrane. Biochem. J. 350:Pt. 1155–62 [Google Scholar]
  7. Santer R, Hillebrand G, Steinmann B, Schaub J. 7.  2003. Intestinal glucose transport: evidence for a membrane traffic-based pathway in humans. Gastroenterology 124:34–39 [Google Scholar]
  8. Burant CF, Takeda J, Brot-Laroche E, Bell GI, Davidson NO. 8.  1992. Fructose transporter in human spermatozoa and small intestine is GLUT5. J. Biol. Chem. 267:14523–26 [Google Scholar]
  9. Abumrad NA, Davidson NO. 9.  2012. Role of the gut in lipid homeostasis. Physiol. Rev. 92:1061–85 [Google Scholar]
  10. Canfora EE, Jocken JW, Blaak EE. 10.  2015. Short-chain fatty acids in control of body weight and insulin sensitivity. Nat. Rev. Endocrinol. 11:577–91 [Google Scholar]
  11. Kosters A, Karpen SJ. 11.  2008. Bile acid transporters in health and disease. Xenobiotica 38:1043–71 [Google Scholar]
  12. Sarkadi B, Homolya L, Szakács G, Váradi A. 12.  2006. Human multidrug resistance ABCB and ABCG transporters: participation in a chemoimmunity defense system. Physiol. Rev. 86:1179–236 [Google Scholar]
  13. Jeon T-I, Seo YK, Osborne TF. 13.  2011. Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving CCK. Biochem. J. 438:33–37 [Google Scholar]
  14. Rehfeld JF.14.  2004. A centenary of gastrointestinal endocrinology. Horm. Metab. Res. 36:735–41 [Google Scholar]
  15. Habib AM, Richards P, Cairns LS, Rogers GJ, Bannon CA. 15.  et al. 2012. Overlap of endocrine hormone expression in the mouse intestine revealed by transcriptional profiling and flow cytometry. Endocrinology 153:3054–65 [Google Scholar]
  16. Solcia E, Rindi G, Buffa R, Fiocca R, Capella C. 16.  2000. Gastric endocrine cells: types, function and growth. Regul. Pept. 93:31–35 [Google Scholar]
  17. Bohórquez DV, Shahid RA, Erdmann A, Kreger AM, Wang Y. 17.  et al. 2015. Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells. J. Clin. Investig. 125:782–86 [Google Scholar]
  18. Müller TD, Nogueiras R, Andermann ML, Andrews ZB, Anker SD. 18.  et al. 2015. Ghrelin. Mol. Metab. 4:437–60 [Google Scholar]
  19. Steinert RE, Beglinger C, Langhans W. 19.  2016. Intestinal GLP-1 and satiation: from man to rodents and back. Int. J. Obes. 40:198–205 [Google Scholar]
  20. Manning S, Batterham RL. 20.  2014. The role of gut hormone peptide YY in energy and glucose homeostasis: twelve years on. Annu. Rev. Physiol. 76:585–608 [Google Scholar]
  21. Rehfeld JF.21.  2017. Cholecystokinin—from local gut hormone to ubiquitous messenger. Front. Endocrinol. 8:47 [Google Scholar]
  22. Jang HJ, Kokrashvili Z, Theodorakis MJ, Carlson OD, Kim BJ. 22.  et al. 2007. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. PNAS 104:15069–74 [Google Scholar]
  23. Steinert RE, Gerspach AC, Gutmann H, Asarian L, Drewe J, Beglinger C. 23.  2011. The functional involvement of gut-expressed sweet taste receptors in glucose-stimulated secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). Clin. Nutr. 30:524–32 [Google Scholar]
  24. Margolskee RF, Dyer J, Kokrashvili Z, Salmon KS, Ilegems E. 24.  et al. 2007. T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1. PNAS 104:15075–80 [Google Scholar]
  25. Gerspach AC, Steinert RE, Schönenberger L, Graber-Maier A, Beglinger C. 25.  2011. The role of the gut sweet taste receptor in regulating GLP-1, PYY, and CCK release in humans. Am. J. Physiol. Endocrinol. Metab. 301:E317–25 [Google Scholar]
  26. Reimann F, Habib AM, Tolhurst G, Parker HE, Rogers GJ, Gribble FM. 26.  2008. Glucose sensing in L cells: a primary cell study. Cell Metab 8:532–39 [Google Scholar]
  27. Parker HE, Adriaenssens A, Rogers G, Richards P, Koepsell H. 27.  et al. 2012. Predominant role of active versus facilitative glucose transport for glucagon-like peptide-1 secretion. Diabetologia 55:2445–55 [Google Scholar]
  28. Gorboulev V, Schürmann A, Vallon V, Kipp H, Jaschke A. 28.  et al. 2011. Na+-D-glucose cotransporter SGLT1 is pivotal for intestinal glucose absorption and glucose-dependent incretin secretion. Diabetes 61:187–96 [Google Scholar]
  29. Nielsen LB, Ploug KB, Swift P, Ørskov C, Jansen-Olesen I. 29.  et al. 2007. Co-localisation of the Kir6.2/SUR1 channel complex with glucagon-like peptide-1 and glucose-dependent insulinotrophic polypeptide expression in human ileal cells and implications for glycaemic control in new onset type 1 diabetes. Eur. J. Endocrinol. 156:663–71 [Google Scholar]
  30. Reimann F, Gribble FM. 30.  2002. Glucose-sensing in glucagon-like peptide-1-secreting cells. Diabetes 51:2757–63 [Google Scholar]
  31. Stephens JW, Bodvarsdottir TB, Wareham K, Prior SL, Bracken RM. 31.  et al. 2011. Effects of short-term therapy with glibenclamide and repaglinide on incretin hormones and oxidative damage associated with postprandial hyperglycaemia in people with type 2 diabetes mellitus. Diabetes Res. Clin. Pract. 94:199–206 [Google Scholar]
  32. Steensels S, Vancleef L, Depoortere I. 32.  2016. The sweetener-sensing mechanisms of the ghrelin cell. Nutrients 8:795 [Google Scholar]
  33. Steensels S, Cools L, Avau B, Vancleef L, Farre R. 33.  et al. 2016. Supplementation of oligofructose, but not sucralose, decreases high-fat diet induced body weight gain in mice independent of gustducin-mediated gut hormone release. Mol. Nutr. Food Res. 61:1600716 [Google Scholar]
  34. Steinert RE, Frey F, Töpfer A, Drewe J, Beglinger C. 34.  2011. Effects of carbohydrate sugars and artificial sweeteners on appetite and the secretion of gastrointestinal satiety peptides. Br. J. Nutr. 105:1320–28 [Google Scholar]
  35. DuBois GE.35.  2016. Molecular mechanism of sweetness sensation. Physiol. Behav. 164:453–63 [Google Scholar]
  36. Engelstoft MS, Park WM, Sakata I, Kristensen LV, Husted AS. 36.  et al. 2013. Seven transmembrane G protein-coupled receptor repertoire of gastric ghrelin cells. Mol. Metab. 2:376–92 [Google Scholar]
  37. Haid DC, Jordan-Biegger C, Widmayer P, Breer H. 37.  2012. Receptors responsive to protein breakdown products in G-cells and D-cells of mouse, swine and human. Front. Physiol. 3:65 [Google Scholar]
  38. Vancleef L, Van Den Broeck T, Thijs T, Steensels S, Briand L. 38.  et al. 2015. Chemosensory signalling pathways involved in sensing of amino acids by the ghrelin cell. Sci. Rep. 5:15725 [Google Scholar]
  39. Nakajima S, Hira T, Hara H. 39.  2012. Calcium-sensing receptor mediates dietary peptide-induced CCK secretion in enteroendocrine STC-1 cells. Mol. Nutr. Food Res. 56:753–60 [Google Scholar]
  40. Liou AP, Sei Y, Zhao X, Feng J, Lu X. 40.  et al. 2011. The extracellular calcium-sensing receptor is required for cholecystokinin secretion in response to L-phenylalanine in acutely isolated intestinal I cells. Am. J. Physiol. Gastrointest. Liver Physiol. 300:G538–46 [Google Scholar]
  41. Oya M, Kitaguchi T, Pais R, Reimann F, Gribble F, Tsuboi T. 41.  2013. The G protein-coupled receptor family C group 6 subtype A (GPRC6A) receptor is involved in amino acid-induced glucagon-like peptide-1 secretion from GLUTag cells. J. Biol. Chem. 288:4513–21 [Google Scholar]
  42. Clemmensen C, Jørgensen CV, Smajilovic S, Brauner-Osborne H. 42.  2016. Robust GLP-1 secretion by basic L-amino acids does not require the GPRC6A receptor. Diabetes Obes. Metab. 19:599–603 [Google Scholar]
  43. Nelson G, Chandrashekar J, Hoon MA, Feng L, Zhao G. 43.  et al. 2002. An amino-acid taste receptor. Nature 416:199–202 [Google Scholar]
  44. Daly K, Al-Rammahi M, Moran A, Marcello M, Ninomiya Y, Shirazi-Beechey SP. 44.  2013. Sensing of amino acids by the gut-expressed taste receptor T1R1-T1R3 stimulates CCK secretion. Am. J. Physiol. Gastrointest. Liver Physiol. 304:G271–82 [Google Scholar]
  45. Choi S, Lee M, Shiu AL, Yo SJ, Halldén G, Aponte GW. 45.  2007. GPR93 activation by protein hydrolysate induces CCK transcription and secretion in STC-1 cells. Am. J. Physiol. Gastrointest. Liver Physiol. 292:G1366–75 [Google Scholar]
  46. Diakogiannaki E, Pais R, Tolhurst G, Parker HE, Horscroft J. 46.  et al. 2013. Oligopeptides stimulate glucagon-like peptide-1 secretion in mice through proton-coupled uptake and the calcium-sensing receptor. Diabetologia 56:2688–96 [Google Scholar]
  47. Pais R, Gribble FM, Reimann F. 47.  2016. Signalling pathways involved in the detection of peptones by murine small intestinal enteroendocrine L-cells. Peptides 77:9–15 [Google Scholar]
  48. Liou AP, Chavez DI, Espero E, Hao S, Wank SA, Raybould HE. 48.  2011. Protein hydrolysate-induced cholecystokinin secretion from enteroendocrine cells is indirectly mediated by the intestinal oligopeptide transporter PepT1. Am. J. Physiol. Gastrointest. Liver Physiol. 300:G895–902 [Google Scholar]
  49. Hara T, Kashihara D, Ichimura A, Kimura I, Tsujimoto G, Hirasawa A. 49.  2014. Role of free fatty acid receptors in the regulation of energy metabolism. Biochim. Biophys. Acta 1841:1292–300 [Google Scholar]
  50. Liou AP, Lu X, Sei Y, Zhao X, Pechhold S. 50.  et al. 2011. The G-protein-coupled receptor GPR40 directly mediates long-chain fatty acid-induced secretion of cholecystokinin. Gastroenterology 140:903–12 [Google Scholar]
  51. Edfalk S, Steneberg P, Edlund H. 51.  2008. Gpr40 is expressed in enteroendocrine cells and mediates free fatty acid stimulation of incretin secretion. Diabetes 57:2280–87 [Google Scholar]
  52. Hirasawa A, Tsumaya K, Awaji T, Katsuma S, Adachi T. 52.  et al. 2005. Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat. Med. 11:90–94 [Google Scholar]
  53. Janssen S, Laermans J, Iwakura H, Tack J, Depoortere I. 53.  2012. Sensing of fatty acids for octanoylation of ghrelin involves a gustatory G-protein. PLOS ONE 7:e40168 [Google Scholar]
  54. Sundaresan S, Shahid R, Riehl TE, Chandra R, Nassir F. 54.  et al. 2013. CD36-dependent signaling mediates fatty acid-induced gut release of secretin and cholecystokinin. FASEB J 27:1191–202 [Google Scholar]
  55. Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM. 55.  et al. 2012. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 61:364–71 [Google Scholar]
  56. Lin HV, Frassetto A, Kowalik EJ Jr., Nawrocki AR, Lu MM. 56.  et al. 2012. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLOS ONE 7:e35240 [Google Scholar]
  57. Pluznick J.57.  2014. A novel SCFA receptor, the microbiota, and blood pressure regulation. Gut Microbes 5:202–7 [Google Scholar]
  58. Fleischer J, Bumbalo R, Bautze V, Strotmann J, Breer H. 58.  2015. Expression of odorant receptor Olfr78 in enteroendocrine cells of the colon. Cell Tissue Res 361:697–710 [Google Scholar]
  59. Overton HA, Fyfe MC, Reynet C. 59.  2008. GPR119, a novel G protein-coupled receptor target for the treatment of type 2 diabetes and obesity. Br. J. Pharmacol. 153:Suppl. 1S76–81 [Google Scholar]
  60. Lan H, Vassileva G, Corona A, Liu L, Baker H. 60.  et al. 2009. GPR119 is required for physiological regulation of glucagon-like peptide-1 secretion but not for metabolic homeostasis. J. Endocrinol. 201:219–30 [Google Scholar]
  61. Moss CE, Glass LL, Diakogiannaki E, Pais R, Lenaghan C. 61.  et al. 2016. Lipid derivatives activate GPR119 and trigger GLP-1 secretion in primary murine L-cells. Peptides 77:16–20 [Google Scholar]
  62. Poreba MA, Dong CX, Li SK, Stahl A, Miner JH, Brubaker PL. 62.  2012. Role of fatty acid transport protein 4 in oleic acid-induced glucagon-like peptide-1 secretion from murine intestinal L cells. Am. J. Physiol. Endocrinol. Metab. 303:E899–907 [Google Scholar]
  63. Van Nierop FS, Scheltema MJ, Eggink HM, Pols TW, Sonne DP. 63.  et al. 2017. Clinical relevance of the bile acid receptor TGR5 in metabolism. Lancet Diabetes Endocrinol 5:224–33 [Google Scholar]
  64. Brighton CA, Rievaj J, Kuhre RE, Glass LL, Schoonjans K. 64.  et al. 2015. Bile acids trigger GLP-1 release predominantly by accessing basolaterally located G protein-coupled bile acid receptors. Endocrinology 156:3961–70 [Google Scholar]
  65. Trabelsi M-S, Daoudi M, Prawitt J, Ducastel S, Touche V. 65.  et al. 2015. Farnesoid X receptor inhibits glucagon-like peptide-1 production by enteroendocrine L cells. Nat. Commun. 6:7629 [Google Scholar]
  66. Avau B, Depoortere I. 66.  2016. The bitter truth about bitter taste receptors: beyond sensing bitter in the oral cavity. Acta Physiol 216:407–20 [Google Scholar]
  67. Rozengurt E.67.  2006. Taste receptors in the gastrointestinal tract. I. Bitter taste receptors and α-gustducin in the mammalian gut. Am. J. Physiol. Gastrointest. Liver Physiol. 291:G171–77 [Google Scholar]
  68. Park J, Kim KS, Kim KH, Lee IS, Jeong HS. 68.  et al. 2015. GLP-1 secretion is stimulated by 1,10-phenanthroline via colocalized T2R5 signal transduction in human enteroendocrine L cell. Biochem. Biophys. Res. Commun. 468:306–11 [Google Scholar]
  69. Latorre R, Huynh J, Mazzoni M, Gupta A, Bonora E. 69.  et al. 2016. Expression of the bitter taste receptor, T2R38, in enteroendocrine cells of the colonic mucosa of overweight/obese vs. lean subjects. PLOS ONE 11:e0147468 [Google Scholar]
  70. Kim KS, Egan JM, Jang HJ. 70.  2014. Denatonium induces secretion of glucagon-like peptide-1 through activation of bitter taste receptor pathways. Diabetologia 57:2117–25 [Google Scholar]
  71. Janssen S, Laermans J, Verhulst PJ, Thijs T, Tack J, Depoortere I. 71.  2011. Bitter taste receptors and α-gustducin regulate the secretion of ghrelin with functional effects on food intake and gastric emptying. PNAS 108:2094–99 [Google Scholar]
  72. Serrano J, Casanova-Martí À, Depoortere I, Blay MT, Terra X. 72.  et al. 2016. Subchronic treatment with grape-seed phenolics inhibits ghrelin production despite a short-term stimulation of ghrelin secretion produced by bitter-sensing flavanols. Mol. Nutr. Food Res. 60:2554–64 [Google Scholar]
  73. Holzer P.73.  2011. TRP channels in the digestive system. Curr. Pharm. Biotechnol. 12:24–34 [Google Scholar]
  74. Nozawa K, Kawabata-Shoda E, Doihara H, Kojima R, Okada H. 74.  et al. 2009. TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells. PNAS 106:3408–13 [Google Scholar]
  75. Camacho S, Michlig S, de Senarclens-Bezencon C, Meylan J, Meystre J. 75.  et al. 2015. Anti-obesity and anti-hyperglycemic effects of cinnamaldehyde via altered ghrelin secretion and functional impact on food intake and gastric emptying. Sci. Rep. 5:7919 [Google Scholar]
  76. Emery EC, Diakogiannaki E, Gentry C, Psichas A, Habib AM. 76.  et al. 2015. Stimulation of GLP-1 secretion downstream of the ligand-gated ion channel TRPA1. Diabetes 64:1202–10 [Google Scholar]
  77. Purhonen AK, Louhivuori LM, Kiehne K, Kerman KE, Herzig KH. 77.  2008. TRPA1 channel activation induces cholecystokinin release via extracellular calcium. FEBS Lett 582:229–32 [Google Scholar]
  78. Kim MJ, Son HJ, Song SH, Jung M, Kim Y, Rhyu MR. 78.  2013. The TRPA1 agonist, methyl syringate suppresses food intake and gastric emptying. PLOS ONE 8:e71603 [Google Scholar]
  79. van Avesaat M, Troost FJ, Westerterp-Plantenga MS, Helyes Z, Le Roux CW. 79.  et al. 2016. Capsaicin-induced satiety is associated with gastrointestinal distress but not with the release of satiety hormones. Am. J. Clin. Nutr. 103:305–13 [Google Scholar]
  80. Smeets AJ, Westerterp-Plantenga MS. 80.  2009. The acute effects of a lunch containing capsaicin on energy and substrate utilisation, hormones, and satiety. Eur. J. Nutr. 48:229–34 [Google Scholar]
  81. Braun T, Voland P, Kunz L, Prinz C, Gratzl M. 81.  2007. Enterochromaffin cells of the human gut: sensors for spices and odorants. Gastroenterology 132:1890–901 [Google Scholar]
  82. Cani PD, Knauf C. 82.  2016. How gut microbes talk to organs: the role of endocrine and nervous routes. Mol. Metab. 5:743–52 [Google Scholar]
  83. Duca FA, Swartz TD, Sakar Y, Covasa M. 83.  2012. Increased oral detection, but decreased intestinal signaling for fats in mice lacking gut microbiota. PLOS ONE 7:e39748 [Google Scholar]
  84. Swartz TD, Duca FA, de Wouters T, Sakar Y, Covasa M. 84.  2012. Up-regulation of intestinal type 1 taste receptor 3 and sodium glucose luminal transporter-1 expression and increased sucrose intake in mice lacking gut microbiota. Br. J. Nutr. 107:621–30 [Google Scholar]
  85. Bogunovic M, Davé SH, Tilstra JS, Chang DT, Harpaz N. 85.  et al. 2007. Enteroendocrine cells express functional Toll-like receptors. Am. J. Physiol. Gastrointest. Liver Physiol. 292:G1770–83 [Google Scholar]
  86. Larraufie P, Doré J, Lapaque N, Blottière HM. 86.  2017. TLR ligands and butyrate increase Pyy expression through two distinct but inter-regulated pathways. Cell. Microbiol. 19:e12648 [Google Scholar]
  87. Sonnenburg JL, Backhed F. 87.  2016. Diet-microbiota interactions as moderators of human metabolism. Nature 535:56–64 [Google Scholar]
  88. Brookes SJ, Spencer NJ, Costa M, Zagorodnyuk VP. 88.  2013. Extrinsic primary afferent signalling in the gut. Nat. Rev. Gastroenterol. Hepatol. 10:286–96 [Google Scholar]
  89. Bertrand PP, Kunze WA, Bornstein JC, Furness JB, Smith ML. 89.  1997. Analysis of the responses of myenteric neurons in the small intestine to chemical stimulation of the mucosa. Am. J. Physiol. 273:G422–35 [Google Scholar]
  90. Liu M, Seino S, Kirchgessner AL. 90.  1999. Identification and characterization of glucoresponsive neurons in the enteric nervous system. J. Neurosci. 19:10305–17 [Google Scholar]
  91. Diez-Sampedro A, Hirayama BA, Osswald C, Gorboulev V, Baumgarten K. 91.  et al. 2003. A glucose sensor hiding in a family of transporters. PNAS 100:11753–58 [Google Scholar]
  92. Rühl A, Hoppe S, Frey I, Daniel H, Schemann M. 92.  2005. Functional expression of the peptide transporter PEPT2 in the mammalian enteric nervous system. J. Comp. Neurol. 490:1–11 [Google Scholar]
  93. Nøhr MK, Pedersen MH, Gille A, Egerod KL, Engelstoft MS. 93.  et al. 2013. GPR41/FFAR3 and GPR43/FFAR2 as cosensors for short-chain fatty acids in enteroendocrine cells vs FFAR3 in enteric neurons and FFAR2 in enteric leukocytes. Endocrinology 154:3552–64 [Google Scholar]
  94. Soret R, Chevalier J, De Coppet P, Poupeau G, Derkinderen P. 94.  et al. 2010. Short-chain fatty acids regulate the enteric neurons and control gastrointestinal motility in rats. Gastroenterology 138:1772–82 [Google Scholar]
  95. Page AJ, Symonds E, Peiris M, Blackshaw LA, Young RL. 95.  2012. Peripheral neural targets in obesity. Br. J. Pharmacol. 166:1537–58 [Google Scholar]
  96. Williams EK, Chang RB, Strochlic DE, Umans BD, Lowell BB, Liberles SD. 96.  2016. Sensory neurons that detect stretch and nutrients in the digestive system. Cell 166:209–21 [Google Scholar]
  97. Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B. 97.  et al. 2003. Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways. Cell 112:293–301 [Google Scholar]
  98. Yu X, Yu M, Liu Y, Yu S. 98.  2016. TRP channel functions in the gastrointestinal tract. Semin. Immunopathol. 38:385–96 [Google Scholar]
  99. Buckinx R, Van Nassauw L, Avula LR, Alpaerts K, Adriaensen D, Timmermans JP. 99.  2013. Transient receptor potential vanilloid type 1 channel (TRPV1) immunolocalization in the murine enteric nervous system is affected by the targeted C-terminal epitope of the applied antibody. J. Histochem. Cytochem. 61:421–32 [Google Scholar]
  100. Liu XJ, Liu T, Chen G, Wang B, Yu XL. 100.  et al. 2016. TLR signaling adaptor protein MyD88 in primary sensory neurons contributes to persistent inflammatory and neuropathic pain and neuroinflammation. Sci. Rep. 6:28188 [Google Scholar]
  101. Burgueño JF, Barba A, Eyre E, Romero C, Neunlist M, Fernández E. 101.  2016. TLR2 and TLR9 modulate enteric nervous system inflammatory responses to lipopolysaccharide. J. Neuroinflamm. 13:187 [Google Scholar]
  102. Höfer D, Püschel B, Drenckhahn D. 102.  1996. Taste receptor-like cells in the rat gut identified by expression of α-gustducin. PNAS 93:6631–34 [Google Scholar]
  103. Hass N, Schwarzenbacher K, Breer H. 103.  2007. A cluster of gustducin-expressing cells in the mouse stomach associated with two distinct populations of enteroendocrine cells. Histochem. Cell Biol. 128:457–71 [Google Scholar]
  104. Hass N, Schwarzenbacher K, Breer H. 104.  2010. T1R3 is expressed in brush cells and ghrelin-producing cells of murine stomach. Cell Tissue Res 339:493–504 [Google Scholar]
  105. Eberle JAM, Richter P, Widmayer P, Chubanov V, Gudermann T, Breer H. 105.  2013. Band-like arrangement of taste-like sensory cells at the gastric groove: evidence for paracrine communication. Front. Physiol. 4:58 [Google Scholar]
  106. Eberle JAM, Widmayer P, Breer H. 106.  2014. Receptors for short-chain fatty acids in brush cells at the “gastric groove.”. Front. Physiol. 5:152 [Google Scholar]
  107. Bezençon C, le Coutre J, Damak S. 107.  2007. Taste-signaling proteins are coexpressed in solitary intestinal epithelial cells. Chem. Senses 32:41–49 [Google Scholar]
  108. Schütz B, Jurastow I, Bader S, Ringer C, von Engelhardt J. 108.  et al. 2015. Chemical coding and chemosensory properties of cholinergic brush cells in the mouse gastrointestinal and biliary tract. Front. Physiol. 6:87 [Google Scholar]
  109. Gerbe F, Sidot E, Smyth DJ, Ohmoto M, Matsumoto I. 109.  et al. 2016. Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites. Nature 529:226–30 [Google Scholar]
  110. Howitt MR, Lavoie S, Michaud M, Blum AM, Tran SV. 110.  et al. 2016. Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut. Science 351:1329–33 [Google Scholar]
  111. von Moltke J, Ji M, Liang HE, Locksley RM. 111.  2016. Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit. Nature 529:221–25 [Google Scholar]
  112. Zhao A, Urban JF Jr., Anthony RM, Sun R, Stiltz J. 112.  et al. 2008. Th2 cytokine-induced alterations in intestinal smooth muscle function depend on alternatively activated macrophages. Gastroenterology 135:217–25.e1 [Google Scholar]
  113. Gersemann M, Wehkamp J, Stange EF. 113.  2012. Innate immune dysfunction in inflammatory bowel disease. J. Intern. Med. 271:421–28 [Google Scholar]
  114. Johansson MEV, Hansson GC. 114.  2016. Immunological aspects of intestinal mucus and mucins. Nat. Rev. Immunol. 16:639–49 [Google Scholar]
  115. Ganz T.115.  2003. Defensins: antimicrobial peptides of innate immunity. Nat. Rev. Immunol. 3:710–20 [Google Scholar]
  116. Mace OJ, Affleck J, Patel N, Kellett GL. 116.  2007. Sweet taste receptors in rat small intestine stimulate glucose absorption through apical GLUT2. J. Physiol. 582:379–92 [Google Scholar]
  117. Prandi S, Bromke M, Hübner S, Voigt A, Boehm U. 117.  et al. 2013. A subset of mouse colonic goblet cells expresses the bitter taste receptor Tas2r131. PLOS ONE 8:e82820 [Google Scholar]
  118. Lee RJ, Kofonow JM, Rosen PL, Siebert AP, Chen B. 118.  et al. 2014. Bitter and sweet taste receptors regulate human upper respiratory innate immunity. J. Clin. Investig. 124:1393–405 [Google Scholar]
  119. Ayabe T, Satchell DP, Wilson CL, Parks WC, Selsted ME, Ouellette AJ. 119.  2000. Secretion of microbicidal α-defensins by intestinal Paneth cells in response to bacteria. Nat. Immunol. 1:113–18 [Google Scholar]
  120. Lala S, Ogura Y, Osborne C, Hor SY, Bromfield A. 120.  et al. 2003. Crohn's disease and the NOD2 gene: a role for Paneth cells. Gastroenterology 125:47–57 [Google Scholar]
  121. Clevers HC, Bevins CL. 121.  2013. Paneth cells: maestros of the small intestinal crypts. Annu. Rev. Physiol. 75:289–311 [Google Scholar]
  122. Maliphol AB, Garth DJ, Medler KF. 122.  2013. Diet-induced obesity reduces the responsiveness of the peripheral taste receptor cells. PLOS ONE 8:e79403 [Google Scholar]
  123. Chevrot M, Bernard A, Ancel D, Buttet M, Martin C. 123.  et al. 2013. Obesity alters the gustatory perception of lipids in the mouse: plausible involvement of lingual CD36. J. Lipid Res. 54:2485–94 [Google Scholar]
  124. Stewart JE, Seimon RV, Otto B, Keast RS, Clifton PM, Feinle-Bisset C. 124.  2011. Marked differences in gustatory and gastrointestinal sensitivity to oleic acid between lean and obese men. Am. J. Clin. Nutr. 93:703–11 [Google Scholar]
  125. Bartoshuk LM, Duffy VB, Hayes JE, Moskowitz HR, Snyder DJ. 125.  2006. Psychophysics of sweet and fat perception in obesity: problems, solutions and new perspectives. Philos. Trans. R. Soc. B 361:1137–48 [Google Scholar]
  126. Scholtz S, Miras AD, Chhina N, Prechtl CG, Sleeth ML. 126.  et al. 2014. Obese patients after gastric bypass surgery have lower brain-hedonic responses to food than after gastric banding. Gut 63:891–902 [Google Scholar]
  127. Little TJ, Isaacs NJ, Young RL, Ott R, Nguyen NQ. 127.  et al. 2014. Characterization of duodenal expression and localization of fatty acid-sensing receptors in humans: relationships with body mass index. Am. J. Physiol. Gastrointest. Liver Physiol. 307:G958–67 [Google Scholar]
  128. Heni M, Müssig K, Machicao F, Machann J, Schick F. 128.  et al. 2011. Variants in the CD36 gene locus determine whole-body adiposity, but have no independent effect on insulin sensitivity. Obesity 19:1004–9 [Google Scholar]
  129. Chambers ES, Viardot A, Psichas A, Morrison DJ, Murphy KG. 129.  et al. 2015. Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut 64:1744–54 [Google Scholar]
  130. van der Beek CM, Canfora EE, Lenaerts K, Troost FJ, Damink SW. 130.  et al. 2016. Distal, not proximal, colonic acetate infusions promote fat oxidation and improve metabolic markers in overweight/obese men. Clin. Sci. 130:2073–82 [Google Scholar]
  131. Dotson CD, Shaw HL, Mitchell BD, Munger SD, Steinle NI. 131.  2010. Variation in the gene TAS2R38 is associated with the eating behavior disinhibition in Old Order Amish women. Appetite 54:93–99 [Google Scholar]
  132. Vegezzi G, Anselmi L, Huynh J, Barocelli E, Rozengurt E. 132.  et al. 2014. Diet-induced regulation of bitter taste receptor subtypes in the mouse gastrointestinal tract. PLOS ONE 9:e107732 [Google Scholar]
  133. Avau B, Bauters D, Steensels S, Vancleef L, Laermans J. 133.  et al. 2015. The gustatory signaling pathway and bitter taste receptors affect the development of obesity and adipocyte metabolism in mice. PLOS ONE 10:e0145538 [Google Scholar]
  134. Avau B, Rotondo A, Thijs T, Andrews CN, Janssen P. 134.  et al. 2015. Targeting extra-oral bitter taste receptors modulates gastrointestinal motility with effects on satiation. Sci. Rep. 5:15985 [Google Scholar]
  135. Deloose E, Janssen P, Corsetti M, Biesiekierski J, Masuy I. 135.  et al. 2017. Intragastric infusion of denatonium benzoate attenuates interdigestive gastric motility and hunger scores in healthy female volunteers. Am. J. Clin. Nutr. 105:580–88 [Google Scholar]
  136. Fushan AA, Simons CT, Slack JP, Drayna D. 136.  2010. Association between common variation in genes encoding sweet taste signaling components and human sucrose perception. Chem. Senses 35:579–92 [Google Scholar]
  137. Fushan AA, Simons CT, Slack JP, Manichaikul A, Drayna D. 137.  2009. Allelic polymorphism within the TAS1R3 promoter is associated with human taste sensitivity to sucrose. Curr. Biol. 19:1288–93 [Google Scholar]
  138. Young RL, Chia B, Isaacs NJ, Ma J, Khoo J. 138.  et al. 2013. Disordered control of intestinal sweet taste receptor expression and glucose absorption in type 2 diabetes. Diabetes 62:3532–41 [Google Scholar]
  139. Nguyen NQ, Debreceni TL, Bambrick JE, Chia B, Wishart J. 139.  et al. 2015. Accelerated intestinal glucose absorption in morbidly obese humans: relationship to glucose transporters, incretin hormones, and glycemia. J. Clin. Endocrinol. Metab. 100:968–76 [Google Scholar]
  140. Rosenstock J, Hansen L, Zee P, Li Y, Cook W. 140.  et al. 2015. Dual add-on therapy in type 2 diabetes poorly controlled with metformin monotherapy: a randomized double-blind trial of saxagliptin plus dapagliflozin addition versus single addition of saxagliptin or dapagliflozin to metformin. Diabetes Care 38:376–83 [Google Scholar]
  141. Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA. 141.  et al. 2014. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 514:181–86 [Google Scholar]
  142. de Ruyter JC, Olthof MR, Seidell JC, Katan MB. 142.  2012. A trial of sugar-free or sugar-sweetened beverages and body weight in children. N. Engl. J. Med. 367:1397–406 [Google Scholar]
  143. Tate DF, Turner-McGrievy G, Lyons E, Stevens J, Erickson K. 143.  et al. 2012. Replacing caloric beverages with water or diet beverages for weight loss in adults: main results of the Choose Healthy Options Consciously Everyday (CHOICE) randomized clinical trial. Am. J. Clin. Nutr. 95:555–63 [Google Scholar]
  144. Mancini AD, Poitout V. 144.  2015. GPR40 agonists for the treatment of type 2 diabetes: life after ‘TAKing’ a hit. Diabetes Obes. Metab. 17:622–29 [Google Scholar]
  145. Steneberg P, Rubins N, Bartoov-Shifman R, Walker MD, Edlund H. 145.  2005. The FFA receptor GPR40 links hyperinsulinemia, hepatic steatosis, and impaired glucose homeostasis in mouse. Cell Metab 1:245–58 [Google Scholar]
  146. Oh DY, Olefsky JM. 146.  2016. G protein-coupled receptors as targets for anti-diabetic therapeutics. Nat. Rev. Drug Discov. 15:161–72 [Google Scholar]
  147. Ichimura A, Hirasawa A, Poulain-Godefroy O, Bonnefond A, Hara T. 147.  et al. 2012. Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human. Nature 483:350–54 [Google Scholar]
  148. Lamri A, Bonnefond A, Meyre D, Balkau B, Roussel R. 148.  et al. 2016. Interaction between GPR120 p.R270H loss-of-function variant and dietary fat intake on incident type 2 diabetes risk in the D.E.S.I.R. study. Nutr. Metab. Cardiovasc. Dis. 26:931–36 [Google Scholar]
  149. Hansen HS, Rosenkilde MM, Holst JJ, Schwartz TW. 149.  2012. GPR119 as a fat sensor. Trends Endocrinol. Metab. 33:374–81 [Google Scholar]
  150. Qu D, Weygant N, May R, Chandrakesan P, Madhoun M. 150.  et al. 2015. Ablation of doublecortin-like kinase 1 in the colonic epithelium exacerbates dextran sulfate sodium-induced colitis. PLOS ONE 10:e0134212 [Google Scholar]
  151. Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F. 151.  et al. 2009. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461:1282–86 [Google Scholar]
  152. Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J. 152.  et al. 2013. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504:451–55 [Google Scholar]
  153. Wang J, Wu X, Simonavicius N, Tian H, Ling L. 153.  2006. Medium-chain fatty acids as ligands for orphan G protein-coupled receptor GPR84. J. Biol. Chem. 281:34457–64 [Google Scholar]
  154. Guo C, Qi H, Yu Y, Zhang Q, Su J. 154.  et al. 2015. The G-protein-coupled bile acid receptor Gpbar1 (TGR5) inhibits gastric inflammation through antagonizing NF-κβ signaling pathway. Front. Pharmacol. 6:287 [Google Scholar]
/content/journals/10.1146/annurev-physiol-021317-121332
Loading
/content/journals/10.1146/annurev-physiol-021317-121332
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error