Review
Special Issue: Neuroendocrine control of appetite
Nutrient sensing in the gut: new roads to therapeutics?

https://doi.org/10.1016/j.tem.2012.11.006Get rights and content

The release of gut hormones involved in the control of food intake is dependent on the acute nutritional status of the body, suggesting that chemosensory mechanisms are involved in the control of their release. G protein-coupled taste receptors similar to those in the lingual system, that respond to sweet, bitter, umami, and fatty acids, are expressed in endocrine cells within the gut mucosa, and coordinate, together with other chemosensory signaling elements, the release of hormones that regulate energy and glucose homeostasis. In health, these nutrient sensors are likely to function as inhibitors to excessive nutrient exposure, and their malfunction may be responsible for a variety of metabolic dysfunctions associated with obesity; they may thus be considered as new therapeutic targets.

Section snippets

Taste: a measure of nutritional qualities of foods

Taste is the sensory modality designed to inform us about the nutritional qualities of the food we eat. For humans this means distinguishing the five basic tastes: sweet, salt, umami, bitter, and sour. Sweet foods signal the presence of carbohydrates that serve as an energy source. Salty taste governs the intake of Na+ and other salts, essential for maintaining the water balance of the body. Umami taste is associated with protein-rich foods. Bitter taste is innately aversive and protects

Map of chemosensory cells in the tongue

Gustatory processing is first achieved at the level of taste receptor cells (TRCs) which are clustered in taste buds on the tongue. Once activated by tastants, TRCs transmit the information via sensory afferent fibers to specific brain areas involved in taste perception. Taste cells are classified into four types depending on their morphological features [2]. Salty taste is transduced by some type I glial-like cells. Type II cells express G protein-coupled receptors (GPCRs) to sense sweet,

The gastrointestinal (GI) system as a sensory organ

The idea that the GI system is a sensory organ became evident when Bayliss and Starling [8] discovered the first gut hormone, secretin, and observed that it was released by luminal acid. Later, it became clear that the GI tract responds to a large array of signals in the lumen, including nutrient and non-nutrient chemicals, mechanical factors, and microorganisms. Recent progress in unraveling the nutrient-sensing mechanisms in the taste buds of the tongue has triggered studies on the existence

Concluding remarks

Our understanding of the molecular pharmacology, physiological function, and therapeutic potential of extra-oral nutrient-sensing receptors is evolving quickly. It is tempting to speculate that obesity and diabetes could be treated by selective targeting of nutrient sensors on endocrine cells to release satiety hormones that are often co-stored in conjunction with insulin from the pancreas, thereby mimicking the physiological effects of a meal and fooling the body that it has eaten. It could

Acknowledgments

This work was supported by grants from the Flemish Foundation for Scientific Research (contract FWO G.0670.10) and by a Methusalem grant from the University of Leuven for research on ‘The Brain–Gut Axis in Health and Disease: from Mucosal Integrity to Cortical Processing’.

Glossary

Cholecystokinin (CCK)
a hormone that circulates in different molecular forms (CCK8, CCK33/39, CCK58) and is secreted from the enteroendocrine K cells in the small intestine in response to fat and proteins. CCK causes the release of digestive enzymes and bile from the pancreas and gallbladder. In addition to its role in digestion, CCK is also a satiety signal that decreases meal size and delays gastric emptying.
Ghrelin
ghrelin is a 28 amino acid peptide with an octanoyl modification at Ser3 which

References (98)

  • N.P. Darcel

    Activation of vagal afferents in the rat duodenum by protein digests requires PepT1

    J. Nutr.

    (2005)
  • P. Steneberg

    The FFA receptor GPR40 links hyperinsulinemia, hepatic steatosis, and impaired glucose homeostasis in mouse

    Cell Metab.

    (2005)
  • C. Gotoh

    The regulation of adipogenesis through GPR120

    Biochem. Biophys. Res. Commun.

    (2007)
  • D.Y. Oh

    GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects

    Cell

    (2010)
  • A.J. Brown

    The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids

    J. Biol. Chem.

    (2003)
  • H.S. Hansen

    GPR119 as a fat sensor

    Trends Pharmacol. Sci.

    (2012)
  • H.M. Cox

    Peptide YY is critical for acylethanolamine receptor Gpr119-induced activation of gastrointestinal mucosal responses

    Cell Metab.

    (2010)
  • H.A. Overton

    Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents

    Cell Metab.

    (2006)
  • A. De Silva

    The gut hormones PYY 3-36 and GLP-1 7-36 amide reduce food intake and modulate brain activity in appetite centers in humans

    Cell Metab.

    (2011)
  • F. Laugerette

    CD36 involvement in orosensory detection of dietary lipids, spontaneous fat preference, and digestive secretions

    J. Clin. Invest.

    (2005)
  • N. Chaudhari

    The cell biology of taste

    J. Cell Biol.

    (2010)
  • W. Meyerhof

    The molecular receptive ranges of human TAS2R bitter taste receptors

    Chem. Senses

    (2010)
  • C. Cartoni

    Taste preference for fatty acids is mediated by GPR40 and GPR120

    J. Neurosci.

    (2010)
  • W. He

    Umami taste responses are mediated by alpha-transducin and alpha-gustducin

    J. Neurosci.

    (2004)
  • G.T. Wong

    Transduction of bitter and sweet taste by gustducin

    Nature

    (1996)
  • E. Sainz

    Functional characterization of human bitter taste receptors

    Biochem. J.

    (2007)
  • W.M. Bayliss

    The mechanism of pancreatic secretion

    J. Physiol.

    (1902)
  • H.R. Berthoud

    Vagal sensors in the rat duodenal mucosa: distribution and structure as revealed by in vivo DiI-tracing

    Anat. Embryol. (Berl.)

    (1995)
  • T.E. Finger

    Solitary chemoreceptor cells in the nasal cavity serve as sentinels of respiration

    Proc. Natl. Acad. Sci. U.S.A.

    (2003)
  • D. Hofer

    Taste receptor-like cells in the rat gut identified by expression of alpha-gustducin

    Proc. Natl. Acad. Sci. U.S.A.

    (1996)
  • C. Bezencon

    Taste-signaling proteins are coexpressed in solitary intestinal epithelial cells

    Chem. Senses

    (2007)
  • K. Sutherland

    Phenotypic characterization of taste cells of the mouse small intestine

    Am. J. Physiol. Gastrointest. Liver Physiol.

    (2007)
  • N. Hass

    A cluster of gustducin-expressing cells in the mouse stomach associated with two distinct populations of enteroendocrine cells

    Histochem. Cell Biol.

    (2007)
  • N. Hass

    T1R3 is expressed in brush cells and ghrelin-producing cells of murine stomach

    Cell Tissue Res.

    (2010)
  • S. Janssen

    Bitter taste receptors and alpha-gustducin regulate the secretion of ghrelin with functional effects on food intake and gastric emptying

    Proc. Natl. Acad. Sci. U.S.A.

    (2011)
  • O.J. Mace

    Sweet taste receptors in rat small intestine stimulate glucose absorption through apical GLUT2

    J. Physiol.

    (2007)
  • A.M. Habib

    Overlap of endocrine hormone expression in the mouse intestine revealed by transcriptional profiling and flow cytometry

    Endocrinology

    (2012)
  • K.L. Egerod

    A major lineage of enteroendocrine cells coexpress CCK, secretin, GIP, GLP-1, PYY, and neurotensin but not somatostatin

    Endocrinology

    (2012)
  • B.C. Field

    Bowels control brain: gut hormones and obesity

    Nat. Rev. Endocrinol.

    (2010)
  • I.M. Brennan

    Effects of fat, protein, and carbohydrate and protein load on appetite, plasma cholecystokinin, peptide YY, and ghrelin, and energy intake in lean and obese men

    Am. J. Physiol. Gastrointest. Liver Physiol.

    (2012)
  • N. Rozengurt

    Colocalization of the alpha-subunit of gustducin with PYY and GLP-1 in L cells of human colon

    Am. J. Physiol. Gastrointest. Liver Physiol.

    (2006)
  • H.J. Jang

    Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1

    Proc. Natl. Acad. Sci. U.S.A.

    (2007)
  • Y. Fujita

    Incretin release from gut is acutely enhanced by sugar but not by sweeteners in vivo

    Am. J. Physiol. Endocrinol. Metab.

    (2009)
  • P. Widmayer

    Altered expression of gustatory-signaling elements in gastric tissue of morbidly obese patients

    Int. J. Obes. (Lond.)

    (2011)
  • E. Rozengurt

    Taste receptors in the gastrointestinal tract. I. Bitter taste receptors and alpha-gustducin in the mammalian gut

    Am. J. Physiol. Gastrointest. Liver Physiol.

    (2006)
  • T.I. Jeon

    SREBP-2 regulates gut peptide secretion through intestinal bitter taste receptor signaling in mice

    J. Clin. Invest.

    (2008)
  • S. Hao

    Role of CCK1 and Y2 receptors in activation of hindbrain neurons induced by intragastric administration of bitter taste receptor ligands

    Am. J. Physiol. Regul. Integr. Comp. Physiol.

    (2008)
  • D.A. Deshpande

    Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction

    Nat. Med.

    (2010)
  • C.D. Dotson

    Bitter taste receptors influence glucose homeostasis

    PLoS ONE

    (2008)
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