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      The Lipid-Sensor Candidates CD36 and GPR120 Are Differentially Regulated by Dietary Lipids in Mouse Taste Buds: Impact on Spontaneous Fat Preference

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          Abstract

          Background

          Recent studies in rodents and humans suggest that the chemoreception of long-chain fatty acids (LCFA) in oral cavity is involved in the spontaneous preference for fatty foods and might contribute to the obesity risk. CD36 and GPR120 are LCFA receptors identified in rodent taste bud cells. The fact that CD36 or GPR120 gene inactivation leads to a decrease in the preference for lipids raises the question of the respective role(s) played by these gustatory lipid-sensor candidates.

          Methodology/Principal Findings

          Using a combination of biochemical, nutritional and behavioural studies in wild-type, CD36 +/− and CD36 −/− mice, it was found that: 1°) CD36 and GPR120 display different diurnal rhythms in the gustatory circumvallate papillae, CD36 mRNA levels being down-regulated during the dark period in contrast to GPR120, 2°) this change is due to food intake and strictly dependent of the presence of lipids in the diet, 3°) CD36 protein levels are also rapidly but transiently decreased by the food intake, a two-fold drop in CD36 protein levels being found 1 h after refeeding, followed by a progressive return to the pre-prandial values, 4°) this down-regulation, which has a post-transcriptional origin, seems sufficient to alter the spontaneous fat preference, independently to change in the GPR120 gene expression.

          Conclusions/Significance

          In contrast to GPR120, CD36 appears to be a food-sensitive lipid sensor in the gustatory circumvallate papillae. Lipid-mediated change in lingual CD36 expression might modulate the motivation for fat during a meal, initially high and then gradually decreasing secondary to the food intake. This short-term lipid-mediated effect is reminiscent of sensory-specific satiety. These findings, which highlight the role played by CD36 in the oro-sensory perception of dietary lipids, raise the possibility of novel pharmacological strategies to modify attraction for fatty foods and decrease obesity risks.

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          Most cited references22

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          The receptors and cells for mammalian taste.

          The emerging picture of taste coding at the periphery is one of elegant simplicity. Contrary to what was generally believed, it is now clear that distinct cell types expressing unique receptors are tuned to detect each of the five basic tastes: sweet, sour, bitter, salty and umami. Importantly, receptor cells for each taste quality function as dedicated sensors wired to elicit stereotypic responses.
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            Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1.

            Glucagon-like peptide-1 (GLP-1), released from gut endocrine L cells in response to glucose, regulates appetite, insulin secretion, and gut motility. How glucose given orally, but not systemically, induces GLP-1 secretion is unknown. We show that human duodenal L cells express sweet taste receptors, the taste G protein gustducin, and several other taste transduction elements. Mouse intestinal L cells also express alpha-gustducin. Ingestion of glucose by alpha-gustducin null mice revealed deficiencies in secretion of GLP-1 and the regulation of plasma insulin and glucose. Isolated small bowel and intestinal villi from alpha-gustducin null mice showed markedly defective GLP-1 secretion in response to glucose. The human L cell line NCI-H716 expresses alpha-gustducin, taste receptors, and several other taste signaling elements. GLP-1 release from NCI-H716 cells was promoted by sugars and the noncaloric sweetener sucralose, and blocked by the sweet receptor antagonist lactisole or siRNA for alpha-gustducin. We conclude that L cells of the gut "taste" glucose through the same mechanisms used by taste cells of the tongue. Modulating GLP-1 secretion in gut "taste cells" may provide an important treatment for obesity, diabetes and abnormal gut motility.
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              T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1.

              Dietary sugars are transported from the intestinal lumen into absorptive enterocytes by the sodium-dependent glucose transporter isoform 1 (SGLT1). Regulation of this protein is important for the provision of glucose to the body and avoidance of intestinal malabsorption. Although expression of SGLT1 is regulated by luminal monosaccharides, the luminal glucose sensor mediating this process was unknown. Here, we show that the sweet taste receptor subunit T1R3 and the taste G protein gustducin, expressed in enteroendocrine cells, underlie intestinal sugar sensing and regulation of SGLT1 mRNA and protein. Dietary sugar and artificial sweeteners increased SGLT1 mRNA and protein expression, and glucose absorptive capacity in wild-type mice, but not in knockout mice lacking T1R3 or alpha-gustducin. Artificial sweeteners, acting on sweet taste receptors expressed on enteroendocrine GLUTag cells, stimulated secretion of gut hormones implicated in SGLT1 up-regulation. Gut-expressed taste signaling elements involved in regulating SGLT1 expression could provide novel therapeutic targets for modulating the gut's capacity to absorb sugars, with implications for the prevention and/or treatment of malabsorption syndromes and diet-related disorders including diabetes and obesity.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2011
                25 August 2011
                : 6
                : 8
                : e24014
                Affiliations
                [1]Physiologie de la Nutrition, INSERM U866, Université de Bourgogne, AgroSup Dijon, Dijon, France
                Institut Pluridisciplinaire Hubert Curien, France
                Author notes

                Conceived and designed the experiments: CM MC DG PP-D PB. Performed the experiments: CM MC DG J-FM PP-D PB. Analyzed the data: CM MC DG PP-D PB. Contributed reagents/materials/analysis tools: CM MC DG J-FM. Wrote the paper: CM PB.

                [¤]

                Current address: Department of Cell & Developmental Biology-Rocky Mountain Taste & Smell Center, University of Colorado Denver, School of Medicine, Aurora, Colorado, United States of America

                Article
                PONE-D-11-03222
                10.1371/journal.pone.0024014
                3162022
                21901153
                6d0ae303-0452-4bd2-a01a-baf49aba4a52
                Martin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 14 February 2011
                : 2 August 2011
                Page count
                Pages: 10
                Categories
                Research Article
                Biology
                Anatomy and Physiology
                Integrative Physiology
                Medicine
                Anatomy and Physiology
                Sensory Systems
                Nutrition
                Obesity

                Uncategorized
                Uncategorized

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