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Robert F. Margolskee - One of the best experts on this subject based on the ideXlab platform.
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Short Title: Fat and Carbohydrate Preferences in Gustducin and Trpm5 Knockout Mice
2016Co-Authors: Anthony Sclafani, John I. Glendinning, Steven Zukerman, Robert F. MargolskeeAbstract:Trpm5 and -Gustducin are key to the transduction of tastes of sugars, amino acids and bitter compounds. This study investigated the role of these signaling proteins in the preference for fat, starch, and starch-derived polysaccharides (Polycose), using Trpm5 knockout (Trpm5 KO) and -Gustducin knockout (Gust KO) mice. In initial two-bottle tests (24 h/day), Trpm5 KO mice showed no preference for soybean oil emulsions (0.313- 2.5%), Polycose solutions (0.5- 4%) or starch suspensions (0.5- 4%). Gust KO mice displayed an attenuated preference for Polycose, but their preference for soybean oil and starch was comparable to that of C57BL/6J wild-type mice (WT). Gust KO mice preferred starch to Polycose whereas WT mice had the opposite preference. Following extensive experience with soybean oil emulsions (Intralipid) and Polycose solutions, the Trpm5 KO mice developed preferences comparable to the WT mice, although their absolute intakes remained suppressed. Similarly, Gust KO mice developed a strong Polycose preference with experience but they continued to consume less than WT mice. These results implicate -Gustducin and Trpm5 as mediators of polysaccharide taste and Trpm5 in fat taste. The disruption in Polycose, but not starch preference, in Gust KO mice indicates that distinct sensory signaling pathways mediate the response to these carbohydrates,. The experience-induced rescue of fat and Polycos
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Contribution of a-Gustducin to Taste-guided Licking Responses of Mice
2014Co-Authors: John I. Glendinning, Robert F. Margolskee, Sami Damak, Lauren D. Bloom, Maika Onishi, Kun Hao Zheng, Alan C. SpectorAbstract:We examined the necessity of a-Gustducin, a G protein a-subunit expressed in taste cells, to taste-mediated licking responses of mice to sapid stimuli. To this end, we measured licking responses of a-Gustducin knock-out (Gus/) mice and heterozygotic littermate controls (Gus+/) to a variety of bitter, umami, sweet, salty and sour taste stimuli. All previous studies of how Gus/ mice ingest taste stimuli have used long-term (i.e. 48 h) preference tests, which may be confounded by post-ingestive and/or experiential effects of the taste stimuli. We minimized these confounds by using a brief-access taste test, which quantifies immediate lick responses to extremely small volumes of sapid solutions. We found that deleting a-Gustducin (i) dramatically reduced the aversiveness of a diverse range of bitter taste stimuli; (ii) moderately decreased appetitive licking to low and in-termediate concentrations of an umami taste stimulus (monosodium glutamate in the presence of 100 lM amiloride), but virtually eliminated the normal aversion to high concentrations of the same taste stimulus; (iii) slightly decreased appetitive licking to sweet taste stimuli; and (iv) modestly reduced the aversiveness of high, but not low or intermediate, concentrations of NaCl. There was no significant effect of deleting a-Gustducin on licking responses to NH4Cl or HCl. Key words: taste, a-Gustducin, brief-access taste test, knock-out mic
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Taste Responses to Sweet Stimuli in a-Gustducin Knockout and Wild-Type Mice
2014Co-Authors: Vicktoria Danilova, Sami Damak, Robert F. MargolskeeAbstract:The importance of a-Gustducin in sweet taste transduction is based on data obtained with sucrose and the artificial sweetener SC45647. Here we studied the role of a-Gustducin in sweet taste. We compared the behavioral and electrophysiological responses of a-Gustducin knockout (KO) and wild-type (WT) mice to 11 different sweeteners, representing carbohydrates, artificial sweeteners, and sweet amino acids. In behavioral experiments, over 48-h preference ratios were measured in two-bottle preference tests. In electrophysiological experiments, integrated responses of chorda tympani (CT) and glossopharyngeal (NG) nerves were recorded.We found that preference ratios of the KOmice were significantly lower than those ofWT for acesulfame
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Electrophysiological Characterization of Voltage-Gated Currents in Defined Taste Cell Types of Mice
2013Co-Authors: Kathryn F. Medler, Robert F. Margolskee, Sue C. KinnamonAbstract:Despite extensive immunological characterization of the cells within taste buds, little is known about the functional significance of the different cell types. In this study, we use taste cells isolated from mouse vallate and foliate papillae to characterize voltage-gated currents in the three principal elongate types of taste cells: type I, II, and III. Cell types are identified by using antibodies to external epitopes [antigen H for type I cells, antigen A for type II cells, and neural cell adhesion molecule (NCAM) for type III cells]. In addition, we identify the subset of type II cells that contains �-Gustducin, a G-protein involved in bitter transduction, by using transgenic mice expressing green fluorescent protein under the control of the Gustducin promoter. Our results indicate that antigen H-immunoreactive (-IR) cells and many of the antigen A-IR cells have small voltage-gated inward Na � and outward K � currents but no voltage-gated Ca 2 � currents. In contrast, a subset of antigen A-IR cells and all NCAM-IR cells have large inward Na � and outward K � currents as well as voltage-gated Ca 2 � currents. Unexpectedly, all Gustducin-expressing cells lacked voltage-gated Ca 2 � currents, suggesting that these cells use mechanisms other than classical synapses to communicate signals to the brain. Key words: taste-cell types; Gustducin; voltage-gated currents; patch-clamp electrophysiology; immunocytochemistry; taste transductio
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targeted taste cell specific overexpression of brain derived neurotrophic factor in adult taste buds elevates phosphorylated trkb protein levels in taste cells increases taste bud size and promotes gustatory innervation
Journal of Biological Chemistry, 2012Co-Authors: Irina V Nosrat, Robert F. Margolskee, Christopher A NosratAbstract:Abstract Brain-derived neurotrophic factor (BDNF) is the most potent neurotrophic factor in the peripheral taste system during embryonic development. It is also expressed in adult taste buds. There is a lack of understanding of the role of BDNF in the adult taste system. To address this, we generated novel transgenic mice in which transgene expression was driven by an α-Gustducin promoter coupling BDNF expression to the postnatal expression of Gustducin in taste cells. Immunohistochemistry revealed significantly stronger BDNF labeling in taste cells of high BDNF-expressing mouse lines compared with controls. We show that taste buds in these mice are significantly larger and have a larger number of taste cells compared with controls. To examine whether innervation was affected in Gust-BDNF mice, we used antibodies to neural cell adhesion molecule (NCAM) and ATP receptor P2X3. The total density of general innervation and specifically the gustatory innervation was markedly increased in high BDNF-expressing mice compared with controls. TrkB and NCAM gene expression in laser capture microdissected taste epithelia were significantly up-regulated in these mice. Up-regulation of TrkB transcripts in taste buds and elevated taste cell-specific TrkB phosphorylation in response to increased BDNF levels indicate that BDNF controls the expression and activation of its high affinity receptor in taste cells. This demonstrates a direct taste cell function for BDNF. BDNF also orchestrates and maintains taste bud innervation. We propose that the Gust-BDNF transgenic mouse models can be employed to further dissect the specific roles of BDNF in the adult taste system.
George L Kellett - One of the best experts on this subject based on the ideXlab platform.
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an energy supply network of nutrient absorption coordinated by calcium and t1r taste receptors in rat small intestine
The Journal of Physiology, 2009Co-Authors: Oliver J Mace, Julie Affleck, George L Kellett, Norma Lister, Emma L Morgan, E J Shepherd, Philip A Helliwell, John R Bronk, David MeredithAbstract:T1R taste receptors are present throughout the gastrointestinal tract. Glucose absorption comprises active absorption via SGLT1 and facilitated absorption via GLUT2 in the apical membrane. Trafficking of apical GLUT2 is rapidly up-regulated by glucose and artificial sweeteners, which act through T1R2 + T1R3/alpha-Gustducin to activate PLC beta2 and PKC betaII. We therefore investigated whether non-sugar nutrients are regulated by taste receptors using perfused rat jejunum in vivo. Under different conditions, we observed a Ca(2+)-dependent reciprocal relationship between the H(+)/oligopeptide transporter PepT1 and apical GLUT2, reflecting the fact that trafficking of PepT1 and GLUT2 to the apical membrane is inhibited and activated by PKC betaII, respectively. Addition of L-glutamate or sucralose to a perfusate containing low glucose (20 mM) each activated PKC betaII and decreased apical PepT1 levels and absorption of the hydrolysis-resistant dipeptide L-Phe(PsiS)-L-Ala (1 mM), while increasing apical GLUT2 and glucose absorption within minutes. Switching perfusion from mannitol to glucose (75 mM) exerted similar effects. c-glutamate induced rapid GPCR internalization of T1R1, T1R3 and transducin, whereas sucralose internalized T1R2, T1R3 and alpha-Gustducin. We conclude that L-glutamate acts via amino acid and glucose via sweet taste receptors to coordinate regulation of PepT1 and apical GLUT2 reciprocally through a common enterocytic pool of PKC betaII. These data suggest the existence of a wider Ca(2+) and taste receptor-coordinated transport network incorporating other nutrients and/or other stimuli capable of activating PKC betaII and additional transporters, such as the aspartate/glutamate transporter, EAAC1, whose level was doubled by L-glutamate. The network may control energy supply.
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sweet taste receptors in rat small intestine stimulate glucose absorption through apical glut2
The Journal of Physiology, 2007Co-Authors: Oliver J Mace, Julie Affleck, Nick Patel, George L KellettAbstract:Natural sugars and artificial sweeteners are sensed by receptors in taste buds. T2R bitter and T1R sweet taste receptors are coupled through G-proteins, alpha-Gustducin and transducin, to activate phospholipase C beta2 and increase intracellular calcium concentration. Intestinal brush cells or solitary chemosensory cells (SCCs) have a structure similar to lingual taste cells and strongly express alpha-Gustducin. It has therefore been suggested over the last decade that brush cells may participate in sugar sensing by a mechanism analogous to that in taste buds. We provide here functional evidence for an intestinal sensing system based on lingual taste receptors. Western blotting and immunocytochemistry revealed that all T1R members are expressed in rat jejunum at strategic locations including Paneth cells, SCCs or the apical membrane of enterocytes; T1Rs are colocalized with each other and with alpha-Gustducin, transducin or phospholipase C beta2 to different extents. Intestinal glucose absorption consists of two components: one is classical active Na+-glucose cotransport, the other is the diffusive apical GLUT2 pathway. Artificial sweeteners increase glucose absorption in the order acesulfame potassium approximately sucralose > saccharin, in parallel with their ability to increase intracellular calcium concentration. Stimulation occurs within minutes by an increase in apical GLUT2, which correlates with reciprocal regulation of T1R2, T1R3 and alpha-Gustducin versus T1R1, transducin and phospholipase C beta2. Our observation that artificial sweeteners are nutritionally active, because they can signal to a functional taste reception system to increase sugar absorption during a meal, has wide implications for nutrient sensing and nutrition in the treatment of obesity and diabetes.
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sweet taste receptors in rat small intestine stimulate glucose absorption through apical glut2
The Journal of Physiology, 2007Co-Authors: Oliver J Mace, Julie Affleck, Nick Patel, George L KellettAbstract:Natural sugars and artificial sweeteners are sensed by receptors in taste buds. T2R bitter and T1R sweet taste receptors are coupled through G-proteins, α-Gustducin and transducin, to activate phospholipase C β2 and increase intracellular calcium concentration. Intestinal brush cells or solitary chemosensory cells (SCCs) have a structure similar to lingual taste cells and strongly express α-Gustducin. It has therefore been suggested over the last decade that brush cells may participate in sugar sensing by a mechanism analogous to that in taste buds. We provide here functional evidence for an intestinal sensing system based on lingual taste receptors. Western blotting and immunocytochemistry revealed that all T1R members are expressed in rat jejunum at strategic locations including Paneth cells, SCCs or the apical membrane of enterocytes; T1Rs are colocalized with each other and with α-Gustducin, transducin or phospholipase C β2 to different extents. Intestinal glucose absorption consists of two components: one is classical active Na+–glucose cotransport, the other is the diffusive apical GLUT2 pathway. Artificial sweeteners increase glucose absorption in the order acesulfame potassium ∼ sucralose > saccharin, in parallel with their ability to increase intracellular calcium concentration. Stimulation occurs within minutes by an increase in apical GLUT2, which correlates with reciprocal regulation of T1R2, T1R3 and α-Gustducin versus T1R1, transducin and phospholipase C β2. Our observation that artificial sweeteners are nutritionally active, because they can signal to a functional taste reception system to increase sugar absorption during a meal, has wide implications for nutrient sensing and nutrition in the treatment of obesity and diabetes.
Oliver J Mace - One of the best experts on this subject based on the ideXlab platform.
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an energy supply network of nutrient absorption coordinated by calcium and t1r taste receptors in rat small intestine
The Journal of Physiology, 2009Co-Authors: Oliver J Mace, Julie Affleck, George L Kellett, Norma Lister, Emma L Morgan, E J Shepherd, Philip A Helliwell, John R Bronk, David MeredithAbstract:T1R taste receptors are present throughout the gastrointestinal tract. Glucose absorption comprises active absorption via SGLT1 and facilitated absorption via GLUT2 in the apical membrane. Trafficking of apical GLUT2 is rapidly up-regulated by glucose and artificial sweeteners, which act through T1R2 + T1R3/alpha-Gustducin to activate PLC beta2 and PKC betaII. We therefore investigated whether non-sugar nutrients are regulated by taste receptors using perfused rat jejunum in vivo. Under different conditions, we observed a Ca(2+)-dependent reciprocal relationship between the H(+)/oligopeptide transporter PepT1 and apical GLUT2, reflecting the fact that trafficking of PepT1 and GLUT2 to the apical membrane is inhibited and activated by PKC betaII, respectively. Addition of L-glutamate or sucralose to a perfusate containing low glucose (20 mM) each activated PKC betaII and decreased apical PepT1 levels and absorption of the hydrolysis-resistant dipeptide L-Phe(PsiS)-L-Ala (1 mM), while increasing apical GLUT2 and glucose absorption within minutes. Switching perfusion from mannitol to glucose (75 mM) exerted similar effects. c-glutamate induced rapid GPCR internalization of T1R1, T1R3 and transducin, whereas sucralose internalized T1R2, T1R3 and alpha-Gustducin. We conclude that L-glutamate acts via amino acid and glucose via sweet taste receptors to coordinate regulation of PepT1 and apical GLUT2 reciprocally through a common enterocytic pool of PKC betaII. These data suggest the existence of a wider Ca(2+) and taste receptor-coordinated transport network incorporating other nutrients and/or other stimuli capable of activating PKC betaII and additional transporters, such as the aspartate/glutamate transporter, EAAC1, whose level was doubled by L-glutamate. The network may control energy supply.
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sweet taste receptors in rat small intestine stimulate glucose absorption through apical glut2
The Journal of Physiology, 2007Co-Authors: Oliver J Mace, Julie Affleck, Nick Patel, George L KellettAbstract:Natural sugars and artificial sweeteners are sensed by receptors in taste buds. T2R bitter and T1R sweet taste receptors are coupled through G-proteins, alpha-Gustducin and transducin, to activate phospholipase C beta2 and increase intracellular calcium concentration. Intestinal brush cells or solitary chemosensory cells (SCCs) have a structure similar to lingual taste cells and strongly express alpha-Gustducin. It has therefore been suggested over the last decade that brush cells may participate in sugar sensing by a mechanism analogous to that in taste buds. We provide here functional evidence for an intestinal sensing system based on lingual taste receptors. Western blotting and immunocytochemistry revealed that all T1R members are expressed in rat jejunum at strategic locations including Paneth cells, SCCs or the apical membrane of enterocytes; T1Rs are colocalized with each other and with alpha-Gustducin, transducin or phospholipase C beta2 to different extents. Intestinal glucose absorption consists of two components: one is classical active Na+-glucose cotransport, the other is the diffusive apical GLUT2 pathway. Artificial sweeteners increase glucose absorption in the order acesulfame potassium approximately sucralose > saccharin, in parallel with their ability to increase intracellular calcium concentration. Stimulation occurs within minutes by an increase in apical GLUT2, which correlates with reciprocal regulation of T1R2, T1R3 and alpha-Gustducin versus T1R1, transducin and phospholipase C beta2. Our observation that artificial sweeteners are nutritionally active, because they can signal to a functional taste reception system to increase sugar absorption during a meal, has wide implications for nutrient sensing and nutrition in the treatment of obesity and diabetes.
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sweet taste receptors in rat small intestine stimulate glucose absorption through apical glut2
The Journal of Physiology, 2007Co-Authors: Oliver J Mace, Julie Affleck, Nick Patel, George L KellettAbstract:Natural sugars and artificial sweeteners are sensed by receptors in taste buds. T2R bitter and T1R sweet taste receptors are coupled through G-proteins, α-Gustducin and transducin, to activate phospholipase C β2 and increase intracellular calcium concentration. Intestinal brush cells or solitary chemosensory cells (SCCs) have a structure similar to lingual taste cells and strongly express α-Gustducin. It has therefore been suggested over the last decade that brush cells may participate in sugar sensing by a mechanism analogous to that in taste buds. We provide here functional evidence for an intestinal sensing system based on lingual taste receptors. Western blotting and immunocytochemistry revealed that all T1R members are expressed in rat jejunum at strategic locations including Paneth cells, SCCs or the apical membrane of enterocytes; T1Rs are colocalized with each other and with α-Gustducin, transducin or phospholipase C β2 to different extents. Intestinal glucose absorption consists of two components: one is classical active Na+–glucose cotransport, the other is the diffusive apical GLUT2 pathway. Artificial sweeteners increase glucose absorption in the order acesulfame potassium ∼ sucralose > saccharin, in parallel with their ability to increase intracellular calcium concentration. Stimulation occurs within minutes by an increase in apical GLUT2, which correlates with reciprocal regulation of T1R2, T1R3 and α-Gustducin versus T1R1, transducin and phospholipase C β2. Our observation that artificial sweeteners are nutritionally active, because they can signal to a functional taste reception system to increase sugar absorption during a meal, has wide implications for nutrient sensing and nutrition in the treatment of obesity and diabetes.
Catia Sternini - One of the best experts on this subject based on the ideXlab platform.
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regulation of α transducin and α Gustducin expression by a high protein diet in the pig gastrointestinal tract
PLOS ONE, 2016Co-Authors: Roberto De Giorgio, Catia Sternini, C. Vallorani, Maurizio Mazzoni, Rocco Latorre, Cristiano Bombardi, Maria Laura Bacci, Monica Forni, Mirella FalconiAbstract:Background The expression of taste receptors (TASRs) and their signalling molecules in the gastrointestinal (GI) epithelial cells, including enteroendocrine cells (EECs), suggests they participate in chemosensing mechanisms influencing GI physiology via the release of endocrine messengers. TASRs mediate gustatory signalling by interacting with different transducers, including α-Gustducin (Gαgust) and α-transducin (Gαtran) G protein subunits. This study tested whether Gαtran and Gαgust immunoreactive (-IR) cells are affected by a short-term (3 days) and long-term (30 days) high protein (Hp) diet in the pig GI tract.
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Regulation of \u3b1-Transducin and \u3b1-Gustducin Expression by a High Protein Diet in the Pig Gastrointestinal Tract
'Public Library of Science (PLoS)', 2016Co-Authors: De Giorgio Roberto, Catia Sternini, Mazzoni Maurizio, Vallorani Claudia, Latorre Rocco, Bombardi Cristiano, Bacci, Maria Laura, Forni Monica, Falconi Mirella, Clavenzani PaoloAbstract:The expression of taste receptors (TASRs) and their signalling molecules in the gastrointestinal (GI) epithelial cells, including enteroendocrine cells (EECs), suggests they participate in chemosensing mechanisms influencing GI physiology via the release of endocrine messengers. TASRs mediate gustatory signalling by interacting with different transducers, including \u3b1-Gustducin (G\u3b1gust) and \u3b1-transducin (G\u3b1tran) G protein subunits. This study tested whether G\u3b1tran and G\u3b1gust immunoreactive (-IR) cells are affected by a short-term (3 days) and long-term (30 days) high protein (Hp) diet in the pig GI tract
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Cells Expressing T2R138 in the Gut.
2014Co-Authors: Gaia Vegezzi, Helen E Raybould, Laura Anselmi, Jennifer Huynh, Elisabetta Barocelli, Enrique Rozengurt, Catia SterniniAbstract:Confocal images of mouse ileum showing colocalization of T2R138 (green) (A) with α-Gustducin (red) (B) immunoreactivity; C: shows overlay of both T2R138 and α-Gustducin immunoreactivity. D–I: Confocal images showing colocalization of T2R138 (green) (D, G) with chromogranin A, a marker of enteroendocrine cells (red) (E, H) and overlay of both immunoreactivities in the same cells (F,I) in the ileum (D–F) and distal colon (G–I). Calibration bar: 20 µm.
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Effect of a High Fat Diet on T2R138, T2R108 and α-Gustducin (Gust) Expression in the Ileum and Colon.
2014Co-Authors: Gaia Vegezzi, Helen E Raybould, Laura Anselmi, Jennifer Huynh, Elisabetta Barocelli, Enrique Rozengurt, Catia SterniniAbstract:qRT-PCR analysis shows that T2R138 mRNA and α-Gustducin mRNA levels are significantly (*p
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TR2138, T2R108 and α-Gustducin (Gust) Regulation by Fasting/Re-feeding in the Stomach.
2014Co-Authors: Gaia Vegezzi, Helen E Raybould, Laura Anselmi, Jennifer Huynh, Elisabetta Barocelli, Enrique Rozengurt, Catia SterniniAbstract:mRNA levels for each transcript were analyzed by qRT-PCR and normalized to β-actin. T2R138, T2R108 and α-Gustducin mRNA levels were markedly decreased by fasting (82%, 53% and 37%, respectively compared to controls) and restored by re-feeding. *p
Inge Depoortere - One of the best experts on this subject based on the ideXlab platform.
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The Sweetener-Sensing Mechanisms of the Ghrelin Cell
Nutrients, 2016Co-Authors: Sandra Steensels, Laurien Vancleef, Inge DepoortereAbstract:Carbohydrate administration decreases plasma levels of the ‘hunger hormone’ ghrelin. The ghrelin cell is co-localized with the sweet taste receptor subunit, TAS1R3, and the gustatory G-protein, Gustducin, both involved in the sensing of sweeteners by entero-endocrine cells. This study investigated the role of Gustducin-mediated sweet taste receptor signaling on ghrelin secretion in a gastric ghrelinoma cell line, tissue segments and mice. The monosaccharide d-glucose and low-intensity sweetener oligofructose (OFS) decreased (p < 0.001) ghrelin secretion while the high-intensity sweetener sucralose increased (p < 0.001) ghrelin secretion in vitro. These effects were not mediated via the sweet taste receptor or glucose transporters (the sodium-dependent glucose cotransporter SGLT-1 and GLUT2). The effect of these compounds was mimicked ex vivo in gastric and jejunal segments from both wild type (WT) and α-Gustducin knockout (α-gust−/−) mice. In vivo, the sensing of d-glucose was polarized since intragastric but not intravenous administration of d-glucose decreased (p < 0.05) ghrelin levels in an α-Gustducin independent manner which involved inhibition of duodenal ghrelin release. In contrast, neither OFS nor sucralose affected ghrelin secretion in vivo. In conclusion, α-Gustducin-mediated sweet taste receptor signaling does not play a functional role in the sensing of carbohydrates, or low- or high-intensity sweeteners by the ghrelin cell.
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Depoortere I. Sensing of fatty acids for octanoylation of ghrelin involves a gustatory G-protein. PLoS One (2012
2016Co-Authors: Sara Janssen, Jorien Laermans, Hiroshi Iwakura, Jan Tack, Inge DepoortereAbstract:Background: Ghrelin is an important regulator of energy – and glucose homeostasis. The octanoylation at Ser3 is essential for ghrelin’s biological effects but the mechanisms involved in the octanoylation are unknown. We investigated whether the gustatory G-protein, a-Gustducin, and the free fatty acid receptors GPR40 and GPR120 are involved in the fatty acid sensing mechanisms of the ghrelin cell. Methods: Wild-type (WT) and a-Gustducin knockout (gust2/2) mice were fed a glyceryl trioctanoate-enriched diet (OD) during 2 weeks. Ghrelin levels and gastric emptying were determined. Co-localization between GPR40, GPR120 and ghrelin or a-Gustducin/a-transducin was investigated by immunofluorescence staining. The role of GPR120 in the effect of medium and long chain fatty acids on the release of ghrelin was studied in the ghrelinoma cell line, MGN3-1. The effect of the GPR40 agonist, MEDICA16, and the GPR120 agonist, grifolic acid, on ghrelin release was studied both in vitro and in vivo. Results: Feeding an OD specifically increased octanoyl ghrelin levels in the stomach of WT mice but not of gust2/2 mice. Gastric emptying was accelerated in WT but not in gust2/2 mice. GPR40 was colocalized with desoctanoyl but not with octanoyl ghrelin, a-Gustducin or a-transducin positive cells in the stomach. GPR120 only colocalized with ghrelin in the duodenum. Addition of octanoic acid or a-linolenic acid to MGN3-1 cells increased and decreased octanoyl ghrelin levels, respectively. Both effects could not be blocked by GPR120 siRNA. MEDICA16 and grifolic acid did not affect ghrelin secretio
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RESEARCH ARTICLE The Gustatory Signaling Pathway and Bitter Taste Receptors Affect the Development of Obesity and Adipocyte Metabolism in Mice
2016Co-Authors: Bert Avau, Jorien Laermans, Jan Tack, Dries Bauters, Laurien Vancleef, Jens Lesuisse, Johan Buyse, Roger H. Lijnen, Ra Steensels, Inge DepoortereAbstract:Intestinal chemosensory signaling pathways involving the gustatory G-protein, Gustducin, and bitter taste receptors (TAS2R) have been implicated in gut hormone release. Alterations in gut hormone profiles may contribute to the success of bariatric surgery. This study investi-gated the involvement of the gustatory signaling pathway in the development of diet-induced obesity and the therapeutic potential of targeting TAS2Rs to induce body weight loss. α-gust-ducin-deficient (α-gust-/-) mice became less obese than wild type (WT) mice when fed a high-fat diet (HFD). White adipose tissue (WAT) mass was lower in α-gust-/- mice due to increased heat production as a result of increases in brown adipose tissue (BAT) thermogenic activity, involving increased protein expression of uncoupling protein 1. Intra-gastric treatment of obeseWT and α-gust-/- mice with the bitter agonists denatonium benzoate (DB) or quinine (Q) during 4 weeks resulted in an α-Gustducin-dependent decrease in body weight gain asso-ciated with a decrease in food intake (DB), but not involving major changes in gut peptide release. BothWAT and 3T3-F442A pre-adipocytes express TAS2Rs. Treatment of pre-adipo-cytes with DB or Q decreased differentiation into mature adipocytes. In conclusion, interfering with the gustatory signaling pathway protects against the development of HFD-induced obe-sity presumably through promoting BAT activity. Intra-gastric bitter treatment inhibits weight gain, possibly by directly affecting adipocyte metabolism
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The Gustatory Signaling Pathway and Bitter Taste Receptors Affect the Development of Obesity and Adipocyte Metabolism in Mice
2015Co-Authors: Bert Avau, Jorien Laermans, Jan Tack, Dries Bauters, Sandra Steensels, Laurien Vancleef, Jens Lesuisse, Johan Buyse, Roger H. Lijnen, Inge DepoortereAbstract:Intestinal chemosensory signaling pathways involving the gustatory G-protein, Gustducin, and bitter taste receptors (TAS2R) have been implicated in gut hormone release. Alterations in gut hormone profiles may contribute to the success of bariatric surgery. This study investigated the involvement of the gustatory signaling pathway in the development of diet-induced obesity and the therapeutic potential of targeting TAS2Rs to induce body weight loss. α-Gustducin-deficient (α-gust-/-) mice became less obese than wild type (WT) mice when fed a high-fat diet (HFD). White adipose tissue (WAT) mass was lower in α-gust-/- mice due to increased heat production as a result of increases in brown adipose tissue (BAT) thermogenic activity, involving increased protein expression of uncoupling protein 1. Intra-gastric treatment of obese WT and α-gust-/- mice with the bitter agonists denatonium benzoate (DB) or quinine (Q) during 4 weeks resulted in an α-Gustducin-dependent decrease in body weight gain associated with a decrease in food intake (DB), but not involving major changes in gut peptide release. Both WAT and 3T3-F442A pre-adipocytes express TAS2Rs. Treatment of pre-adipocytes with DB or Q decreased differentiation into mature adipocytes. In conclusion, interfering with the gustatory signaling pathway protects against the development of HFD-induced obesity presumably through promoting BAT activity. Intra-gastric bitter treatment inhibits weight gain, possibly by directly affecting adipocyte metabolism.
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Immunofluorescence colocalization studies between GPR40 and ghrelin or the gustatory G-proteins in sections of the mouse stomach and duodenum.
2013Co-Authors: Sara Janssen, Jorien Laermans, Hiroshi Iwakura, Jan Tack, Inge DepoortereAbstract:(A) Double-immunofluorescence staining showing colocalization between anti-GPR40 staining (red) and anti-total ghrelin staining (green) in endocrine cells. (B) GPR40 (red) immunoreactive endocrine cells did not colocalize with octanoyl ghrelin (green) immunoreactive endocrine cells, but some GPR40 positive cells were in close proximity with octanoyl ghrelin positive cells as pointed by the arrow. (C) No colocalization of GPR40 (red) and α-transducin (green) in stomach endocrine cells. (D) Double staining of GPR40 (red) and α-Gustducin (green) in endocrine cells. (E) Double staining between GPR40 (red) and total ghrelin (green) in mouse duodenum. No colocalization is detected. Bar = 25 µm.