Skip to main content
×
Home
    • Aa
    • Aa

Nutrient sensing and signalling by the gut

  • Rojo Rasoamanana (a1) (a2), Nicolas Darcel (a1), Gilles Fromentin (a2) and Daniel Tomé (a1)
Abstract

Recent advances highlight that nutrient receptors (such as T1R1/T1R3 heterodimer, Ca sensing receptor and GPR93 for amino acids and protein, GPR40, GPR41, GPR43 and GPR120 for fatty acids, T1R2/T1R3 heterodimer for monosaccharides) are expressed in the apical face of the gut and sense nutrients in the lumen. They transduce signals for the regulation of nutrient transporter expressions in the apical face. Interestingly, they are also localised in enteroendocrine cells (EEC) and mainly exert a direct control on the secretion in the lamina propria of gastro-intestinal peptides such as cholecystokinin, glucagon-like peptide-1 and peptide YY in response to energy nutrient transit and absorption in the gut. This informs central nuclei involved in the control of feeding such as the hypothalamus and nucleus of the solitary tract of the availability of these nutrients and thus triggers adaptive responses to maintain energy homoeostasis. These nutrient receptors then have a prominent position since they manage nutrient absorption and are principally the generator of the first signal of satiation mechanisms mainly transmitted to the brain by vagal afferents. Moreover, tastants are also able to elicit gut peptides secretion via chemosensory receptors expressed in EEC. Targeting these nutrient and tastant receptors in EEC may thus be helpful to promote satiation and so to fight overfeeding and its consequences.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Nutrient sensing and signalling by the gut
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about sending content to Dropbox.

      Nutrient sensing and signalling by the gut
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about sending content to Google Drive.

      Nutrient sensing and signalling by the gut
      Available formats
      ×
Copyright
Corresponding author
* Corresponding author: Professor Daniel Tomé, fax +33 144087248, email tome@agroparistech.fr
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

2. A Hirasawa , K Tsumaya , T Awaji , (2005) Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat Med 11, 9094.

3. X Li , L Staszewski , H Xu , (2002) Human receptors for sweet and umami taste. Proc Natl Acad Sci USA 99, 46924696.

4. JE Blevins & DG Baskin (2010) Hypothalamic-brainstem circuits controlling eating. Forum Nutr 63, 133140.

5. DE Cummings & J Overduin (2007) Gastrointestinal regulation of food intake. J Clin Invest 117, 1323.

6. HJ Grill & MR Hayes (2009) The nucleus tractus solitarius: a portal for visceral afferent signal processing, energy status assessment and integration of their combined effects on food intake. Int J Obes 33, Suppl. 1, S11S15.

7. N Delzenne , J Blundell , F Brouns , (2010) Gastrointestinal targets of appetite regulation in humans. Obes Rev 11, 234250.

8. MT Neary & RL Batterham (2009) Gut hormones: implications for the treatment of obesity. Pharmacol Ther 124, 4456.

9. TH Moran & MJ Dailey (2011) Intestinal feedback signaling and satiety. Physiol Behav 105, 7781.

10. D Grundy (2006) Signalling the state of the digestive tract. Auton Neurosci 125, 7680.

11. RE Steinert & C Beglinger (2011) Nutrient sensing in the gut: interactions between chemosensory cells, visceral afferents and the secretion of satiation peptides. Physiol Behav 105, 6270.

14. CR Abbott , M Monteiro , CJ Small , (2005) The inhibitory effects of peripheral administration of peptide YY(3–36) and glucagon-like peptide-1 on food intake are attenuated by ablation of the vagal-brainstem-hypothalamic pathway. Brain Res 1044, 127131.

15. EB Ruttimann , M Arnold , JJ Hillebrand , (2009) Intrameal hepatic portal and intraperitoneal infusions of glucagon-like peptide-1 reduce spontaneous meal size in the rat via different mechanisms. Endocrinology 150, 11741181.

17. GW Cheung , A Kokorovic , CK Lam , (2009) Intestinal cholecystokinin controls glucose production through a neuronal network. Cell Metab 10, 99–109.

19. J Chandrashekar , KL Mueller , MA Hoon , (2000) T2Rs function as bitter taste receptors. Cell 100, 703711.

20. GT Wong , KS Gannon & RF Margolskee (1996) Transduction of bitter and sweet taste by gustducin. Nature 381, 796800.

21. W He , K Yasumatsu , V Varadarajan , (2004) Umami taste responses are mediated by alpha-transducin and alpha-gustducin. J Neurosci 24, 76747680.

22. D Liu & ER Liman (2003) Intracellular Ca2+ and the phospholipid PIP2 regulate the taste transduction ion channel TRPM5. Proc Natl Acad Sci USA 100, 1516015165.

23. C Bezencon , J le Coutre & S Damak (2007) Taste-signaling proteins are coexpressed in solitary intestinal epithelial cells. Chem Senses 32, 4149.

24. J Dyer , KS Salmon , L Zibrik , (2005) Expression of sweet taste receptors of the T1R family in the intestinal tract and enteroendocrine cells. Biochem Soc Trans 33, 302305.

25. OJ Mace , J Affleck , N Patel , (2007) Sweet taste receptors in rat small intestine stimulate glucose absorption through apical GLUT2. J Physiol 582, 379392.

27. SV Wu , N Rozengurt , M Yang , (2002) Expression of bitter taste receptors of the T2R family in the gastrointestinal tract and enteroendocrine STC-1 cells. Proc Natl Acad Sci USA 99, 23922397.

28. SV Wu , MC Chen & E Rozengurt (2005) Genomic organization, expression, and function of bitter taste receptors (T2R) in mouse and rat. Physiol Genomics 22, 139149.

30. CI Cheeseman (1993) GLUT2 is the transporter for fructose across the rat intestinal basolateral membrane. Gastroenterology 105, 10501056.

31. RF Margolskee , J Dyer , Z Kokrashvili , (2007) T1R3 and gustducin in gut sense sugars to regulate expression of Na + -glucose cotransporter 1. Proc Natl Acad Sci USA 104, 1507515080.

32. J Dyer , K Daly , KS Salmon , (2007) Intestinal glucose sensing and regulation of intestinal glucose absorption. Biochem Soc Trans 35, 11911194.

33. V Tobin , M Le Gall , X Fioramonti , (2008) Insulin internalizes GLUT2 in the enterocytes of healthy but not insulin-resistant mice. Diabetes 57, 555562.

34. E Rozengurt & C Sternini (2007) Taste receptor signaling in the mammalian gut. Curr Opin Pharmacol 7, 557562.

35. AC Gerspach , RE Steinert , L Schonenberger , (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, E317E325.

37. HJ Jang , Z Kokrashvili , MJ Theodorakis , (2007) Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci USA 104, 1506915074.

39. MC Geraedts , FJ Troost & WH Saris (2011) Different tastants and low-caloric sweetners induce differential effects on the release of satiety hormones. Food Chem 129, 8.

40. LJ Karhunen , KR Juvonen , A Huotari , (2008) Effect of protein, fat, carbohydrate and fibre on gastrointestinal peptide release in humans. Regul Pept 149, 7078.

41. GQ Zhao , Y Zhang , MA Hoon , (2003) The receptors for mammalian sweet and umami taste. Cell 115, 255266.

42. G Nelson , J Chandrashekar , MA Hoon , (2002) An amino-acid taste receptor. Nature 416, 199202.

43. N Chaudhari , AM Landin & SD Roper (2000) A metabotropic glutamate receptor variant functions as a taste receptor. Nat Neurosci 3, 113119.

44. LA Blackshaw , AJ Page & RL Young (2011) Metabotropic glutamate receptors as novel therapeutic targets on visceral sensory pathways. Front Neurosci 5, 40.

45. AD Conigrave , SJ Quinn & EM Brown (2000) L-amino acid sensing by the extracellular Ca2+-sensing receptor. Proc Natl Acad Sci USA 97, 48144819.

46. AD Conigrave , HC Mun , L Delbridge , (2004) L-amino acids regulate parathyroid hormone secretion. J Biol Chem 279, 3815138159.

48. SC Hebert , S Cheng & J Geibel (2004) Functions and roles of the extracellular Ca2+-sensing receptor in the gastrointestinal tract. Cell Calcium 35, 239247.

49. E Nakamura , M Hasumura , H Uneyama , (2011) Luminal amino acid-sensing cells in gastric mucosa. Digestion 83, Suppl. 1, 1318.

50. M Pi , P Faber , G Ekema , (2005) Identification of a novel extracellular cation-sensing G-protein-coupled receptor. J Biol Chem 280, 4020140209.

51. HS Hundal & PM Taylor (2009) Amino acid transceptors: gate keepers of nutrient exchange and regulators of nutrient signaling. Am J Physiol Endocrinol Metab 296, E603E613.

52. S Broer (2008) Apical transporters for neutral amino acids: physiology and pathophysiology. Physiology 23, 95–103.

53. D Herrera-Ruiz , Q Wang , OS Gudmundsson , (2001) Spatial expression patterns of peptide transporters in the human and rat gastrointestinal tracts, Caco-2 in vitro cell culture model, and multiple human tissues. AAPS Pharm Sci 3, E9.

54. H Shen , DE Smith & FC Brosius III (2001) Developmental expression of PEPT1 and PEPT2 in rat small intestine, colon, and kidney. Pediatr Res 49, 789795.

55. I Rubio-Aliaga & H Daniel (2002) Mammalian peptide transporters as targets for drug delivery. Trends Pharmacol Sci 23, 434440.

56. Y Hu , DE Smith , K Ma , (2008) Targeted disruption of peptide transporter Pept1 gene in mice significantly reduces dipeptide absorption in intestine. Mol Pharm 5, 11221130.

57. MS Kilberg , YX Pan , H Chen , (2005) Nutritional control of gene expression: how mammalian cells respond to amino acid limitation. Annu Rev Nutr 25, 5985.

58. N Chotechuang , D Azzout-Marniche , C Bos , (2009) mTOR, AMPK, and GCN2 coordinate the adaptation of hepatic energy metabolic pathways in response to protein intake in the rat. Am J Physiol Endocrinol Metab 297, E1313E1323.

59. J Avruch , X Long , S Ortiz-Vega , (2009) Amino acid regulation of TOR complex 1. Am J Physiol Endocrinol Metab 296, E592E602.

60. A Bensaid , D Tome , D Gietzen , (2002) Protein is more potent than carbohydrate for reducing appetite in rats. Physiol Behav 75, 577582.

62. CA Leech & JF Habener (2003) Regulation of glucagon-like peptide-1 receptor and calcium-sensing receptor signaling by L-histidine. Endocrinology 144, 48514858.

63. T Hira , S Nakajima , Y Eto , (2008) Calcium-sensing receptor mediates phenylalanine-induced cholecystokinin secretion in enteroendocrine STC-1 cells. FEBS J 275, 46204626.

64. S Nakajima , T Hira , Y Eto , (2010) Soybean beta 51–63 peptide stimulates cholecystokinin secretion via a calcium-sensing receptor in enteroendocrine STC-1 cells. Regul Pept 159, 148155.

65. M Cordier-Bussat , C Bernard , S Haouche , (1997) Peptones stimulate cholecystokinin secretion and gene transcription in the intestinal cell line STC-1. Endocrinology 138, 11371144.

66. M Cordier-Bussat , C Bernard , F Levenez , (1998) Peptones stimulate both the secretion of the incretin hormone glucagon-like peptide 1 and the transcription of the proglucagon gene. Diabetes 47, 10381045.

70. K Matsumura , T Miki , T Jhomori , (2005) Possible role of PEPT1 in gastrointestinal hormone secretion. Biochem Biophys Res Commun 336, 10281032.

72. S Edfalk , P Steneberg & H Edlund (2008) Gpr40 is expressed in enteroendocrine cells and mediates free fatty acid stimulation of incretin secretion. Diabetes 57, 22802287.

73. AJ Brown , SM Goldsworthy , AA Barnes , (2003) The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem 278, 1131211319.

74. S Miyauchi , A Hirasawa , A Ichimura , (2010) New frontiers in gut nutrient sensor research: free fatty acid sensing in the gastrointestinal tract. J Pharmacol Sci 112, 1924.

75. LM Lauffer , R Iakoubov & PL Brubaker (2009) GPR119 is essential for oleoylethanolamide-induced glucagon-like peptide-1 secretion from the intestinal enteroendocrine L-cell. Diabetes 58, 10581066.

76. A Stahl , DJ Hirsch , RE Gimeno , (1999) Identification of the major intestinal fatty acid transport protein. Mol Cell 4, 299308.

77. VA Drover , DV Nguyen , CC Bastie , (2008) CD36 mediates both cellular uptake of very long chain fatty acids and their intestinal absorption in mice. J Biol Chem 283, 1310813115.

78. F Nassir , B Wilson , X Han , (2007) CD36 is important for fatty acid and cholesterol uptake by the proximal but not distal intestine. J Biol Chem 282, 1949319501.

79. J Shim , CL Moulson , EP Newberry , (2009) Fatty acid transport protein 4 is dispensable for intestinal lipid absorption in mice. J Lipid Res 50, 491500.

80. DM Breen , CS Yang & TK Lam (2011) Gut-brain signalling: how lipids can trigger the gut. Diabetes Metab Res Rev 27, 113119.

81. HJ Binder (2010) Role of colonic short-chain fatty acid transport in diarrhea. Annu Rev Physiol 72, 297313.

82. C Feinle-Bisset , M Patterson , MA Ghatei , (2005) Fat digestion is required for suppression of ghrelin and stimulation of peptide YY and pancreatic polypeptide secretion by intraduodenal lipid. Am J Physiol Endocrinol Metab 289, E948E953.

83. T Tanaka , S Katsuma , T Adachi , (2008) Free fatty acids induce cholecystokinin secretion through GPR120. Naunyn-Schmiedeberg's Arch Pharmacol 377, 523527.

85. AP Liou , X Lu , Y Sei , (2011) The G-protein-coupled receptor GPR40 directly mediates long-chain fatty acid-induced secretion of cholecystokinin. Gastroenterology 140, 903912.

86. MJ Dailey , KL Tamashiro , CE Terrillion , (2010) Nutrient specific feeding and endocrine effects of jejunal infusions. Obesity 18, 904910.

87. J Maljaars , EA Romeyn , E Haddeman , (2009) Effect of fat saturation on satiety, hormone release, and food intake. Am J Clin Nutr 89, 10191024.

88. PW Maljaars , T Symersky , BC Kee , (2008) Effect of ileal fat perfusion on satiety and hormone release in healthy volunteers. Int J Obes (2005) 32, 16331639.

89. KV Hand , CM Bruen , F O'Halloran , (2010) Acute and chronic effects of dietary fatty acids on cholecystokinin expression, storage and secretion in enteroendocrine STC-1 cells. Mol Nutr Food Res 54, Suppl. 1, S93–S103.

91. S Karaki , R Mitsui , H Hayashi , (2006) Short-chain fatty acid receptor, GPR43, is expressed by enteroendocrine cells and mucosal mast cells in rat intestine. Cell Tissue Res 324, 353360.

92. H Tazoe , Y Otomo , S Karaki , (2009) Expression of short-chain fatty acid receptor GPR41 in the human colon. Biomed Res 30, 149156.

93. BS Samuel , A Shaito , T Motoike , (2008) Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci USA 105, 1676716772.

94. KB Hansen , MM Rosenkilde , FK Knop , (2011) 2-Oleoyl glycerol is a GPR119 agonist and signals GLP-1 release in humans. J Clin Endocrinol Metab 96, E1409E1417.

95. J Glatzle , N Darcel , AJ Rechs , (2004) Apolipoprotein A-IV stimulates duodenal vagal afferent activity to inhibit gastric motility via a CCK1 pathway. Am J Physiol Regul Integr Comp Physiol 287, R354R359.

97. PY Wang , L Caspi , CK Lam , (2008) Upper intestinal lipids trigger a gut-brain-liver axis to regulate glucose production. Nature 452, 10121016.

98. Z Hu , Y Dai , M Prentki , (2005) A role for hypothalamic malonyl-CoA in the control of food intake. J Biol Chem 280, 3968139683.

99. BB Kahn , T Alquier , D Carling , (2005) AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 1, 1525.

100. TM Loftus , DE Jaworsky , GL Frehywot , (2000) Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors. Science 288, 23792381.

101. S Janssen , J Laermans , PJ Verhulst , (2011) Bitter taste receptors and alpha-gustducin regulate the secretion of ghrelin with functional effects on food intake and gastric emptying. Proc Natl Acad Sci USA 108, 20942099.

102. J Schwarz , J Burguet , O Rampin , (2010) Three-dimensional macronutrient-associated Fos expression patterns in the mouse brainstem. PloS One 5, e8974.

106. W Nefti , C Chaumontet , G Fromentin , (2009) A high-fat diet attenuates the central response to within-meal satiation signals and modifies the receptor expression of vagal afferents in mice. Am J Physiol Regul Integr Comp Physiol 296, R1681R1686.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Proceedings of the Nutrition Society
  • ISSN: 0029-6651
  • EISSN: 1475-2719
  • URL: /core/journals/proceedings-of-the-nutrition-society
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords:

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 41
Total number of PDF views: 220 *
Loading metrics...

Abstract views

Total abstract views: 313 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 23rd June 2017. This data will be updated every 24 hours.