Exposure of <i>Caenorhabditis elegans</i> to Dietary <i>Nε</i>-Carboxymethyllysine Emphasizes Endocytosis as a New Route for Intestinal Absorption of Advanced Glycation End Products
The impact of dietary advanced glycation end products (dAGEs) on human health has been discussed in many studies but, to date, no consensual pathophysiological process has been demonstrated. The intestinal absorption pathways which have so far been described for dAGEs, the passive diffusion of free...
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MDPI AG
2021-12-01
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| Online Access: | https://www.mdpi.com/2072-6643/13/12/4398 |
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| author | Constance Dubois Rachel Litke Stéphane Rianha Charles Paul-Constant Jean-Marc Lo Guidice Solenne Taront Frédéric J. Tessier Eric Boulanger Chantal Fradin |
| author_facet | Constance Dubois Rachel Litke Stéphane Rianha Charles Paul-Constant Jean-Marc Lo Guidice Solenne Taront Frédéric J. Tessier Eric Boulanger Chantal Fradin |
| author_sort | Constance Dubois |
| collection | DOAJ |
| description | The impact of dietary advanced glycation end products (dAGEs) on human health has been discussed in many studies but, to date, no consensual pathophysiological process has been demonstrated. The intestinal absorption pathways which have so far been described for dAGEs, the passive diffusion of free AGE adducts and transport of glycated di-tripeptides by the peptide transporter 1 (PEPT-1), are not compatible with certain pathophysiological processes described. To get new insight into the intestinal absorption pathways and the pathophysiological mechanisms of dAGEs, we initiated an in vivo study with a so-called simple animal model with a complete digestive tract, <i>Caenorhabditis elegans</i>. Dietary bacteria were chemically modified with glyoxylic acid to mainly produce <i>Nε</i>-carboxymethyllysine (CML) and used to feed the worms. We performed different immunotechniques using an anti-CML antibody for the relative quantification of ingested CML and localization of this AGE in the worms’ intestine. The relative expression of genes encoding different biological processes such as response to stresses and intestinal digestion were determined. The physiological development of the worms was verified. All the results were compared with those obtained with the control bacteria. The results revealed a new route for the intestinal absorption of dietary CML (dCML), endocytosis, which could be mediated by scavenger receptors. The exposure of worms to dCML induced a reproductive defect and a transcriptional response reflecting oxidative, carbonyl and protein folding stresses. These data, in particular the demonstration of endocytosis of dCML by enterocytes, open up new perspectives to better characterize the pathophysiological mechanisms of dAGEs. |
| first_indexed | 2024-03-10T03:23:48Z |
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| language | English |
| last_indexed | 2024-03-10T03:23:48Z |
| publishDate | 2021-12-01 |
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| series | Nutrients |
| spelling | doaj.art-cffe7e41ef78449bba7b56fb3a762bb32023-11-23T09:57:10ZengMDPI AGNutrients2072-66432021-12-011312439810.3390/nu13124398Exposure of <i>Caenorhabditis elegans</i> to Dietary <i>Nε</i>-Carboxymethyllysine Emphasizes Endocytosis as a New Route for Intestinal Absorption of Advanced Glycation End ProductsConstance Dubois0Rachel Litke1Stéphane Rianha2Charles Paul-Constant3Jean-Marc Lo Guidice4Solenne Taront5Frédéric J. Tessier6Eric Boulanger7Chantal Fradin8Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Facteurs de Risque et Déterminants Moléculaires des Maladies Liées au Vieillissement, F-59000 Lille, FranceUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Facteurs de Risque et Déterminants Moléculaires des Maladies Liées au Vieillissement, F-59000 Lille, FranceUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Facteurs de Risque et Déterminants Moléculaires des Maladies Liées au Vieillissement, F-59000 Lille, FranceUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Facteurs de Risque et Déterminants Moléculaires des Maladies Liées au Vieillissement, F-59000 Lille, FranceUniv. Lille, CHU Lille, Institut Pasteur de Lille, ULR 4483-IMPECS-IMPact de l’Environnement Chimique sur la Santé Humaine, F-59000 Lille, FranceUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Facteurs de Risque et Déterminants Moléculaires des Maladies Liées au Vieillissement, F-59000 Lille, FranceUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Facteurs de Risque et Déterminants Moléculaires des Maladies Liées au Vieillissement, F-59000 Lille, FranceUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Facteurs de Risque et Déterminants Moléculaires des Maladies Liées au Vieillissement, F-59000 Lille, FranceUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Facteurs de Risque et Déterminants Moléculaires des Maladies Liées au Vieillissement, F-59000 Lille, FranceThe impact of dietary advanced glycation end products (dAGEs) on human health has been discussed in many studies but, to date, no consensual pathophysiological process has been demonstrated. The intestinal absorption pathways which have so far been described for dAGEs, the passive diffusion of free AGE adducts and transport of glycated di-tripeptides by the peptide transporter 1 (PEPT-1), are not compatible with certain pathophysiological processes described. To get new insight into the intestinal absorption pathways and the pathophysiological mechanisms of dAGEs, we initiated an in vivo study with a so-called simple animal model with a complete digestive tract, <i>Caenorhabditis elegans</i>. Dietary bacteria were chemically modified with glyoxylic acid to mainly produce <i>Nε</i>-carboxymethyllysine (CML) and used to feed the worms. We performed different immunotechniques using an anti-CML antibody for the relative quantification of ingested CML and localization of this AGE in the worms’ intestine. The relative expression of genes encoding different biological processes such as response to stresses and intestinal digestion were determined. The physiological development of the worms was verified. All the results were compared with those obtained with the control bacteria. The results revealed a new route for the intestinal absorption of dietary CML (dCML), endocytosis, which could be mediated by scavenger receptors. The exposure of worms to dCML induced a reproductive defect and a transcriptional response reflecting oxidative, carbonyl and protein folding stresses. These data, in particular the demonstration of endocytosis of dCML by enterocytes, open up new perspectives to better characterize the pathophysiological mechanisms of dAGEs.https://www.mdpi.com/2072-6643/13/12/4398advanced glycation end products (AGEs)<i>Nε</i>-carboxymethyllysine (CML)<i>Caenorhabditis elegans</i>intestineabsorptionenterocyte |
| spellingShingle | Constance Dubois Rachel Litke Stéphane Rianha Charles Paul-Constant Jean-Marc Lo Guidice Solenne Taront Frédéric J. Tessier Eric Boulanger Chantal Fradin Exposure of <i>Caenorhabditis elegans</i> to Dietary <i>Nε</i>-Carboxymethyllysine Emphasizes Endocytosis as a New Route for Intestinal Absorption of Advanced Glycation End Products Nutrients advanced glycation end products (AGEs) <i>Nε</i>-carboxymethyllysine (CML) <i>Caenorhabditis elegans</i> intestine absorption enterocyte |
| title | Exposure of <i>Caenorhabditis elegans</i> to Dietary <i>Nε</i>-Carboxymethyllysine Emphasizes Endocytosis as a New Route for Intestinal Absorption of Advanced Glycation End Products |
| title_full | Exposure of <i>Caenorhabditis elegans</i> to Dietary <i>Nε</i>-Carboxymethyllysine Emphasizes Endocytosis as a New Route for Intestinal Absorption of Advanced Glycation End Products |
| title_fullStr | Exposure of <i>Caenorhabditis elegans</i> to Dietary <i>Nε</i>-Carboxymethyllysine Emphasizes Endocytosis as a New Route for Intestinal Absorption of Advanced Glycation End Products |
| title_full_unstemmed | Exposure of <i>Caenorhabditis elegans</i> to Dietary <i>Nε</i>-Carboxymethyllysine Emphasizes Endocytosis as a New Route for Intestinal Absorption of Advanced Glycation End Products |
| title_short | Exposure of <i>Caenorhabditis elegans</i> to Dietary <i>Nε</i>-Carboxymethyllysine Emphasizes Endocytosis as a New Route for Intestinal Absorption of Advanced Glycation End Products |
| title_sort | exposure of i caenorhabditis elegans i to dietary i nε i carboxymethyllysine emphasizes endocytosis as a new route for intestinal absorption of advanced glycation end products |
| topic | advanced glycation end products (AGEs) <i>Nε</i>-carboxymethyllysine (CML) <i>Caenorhabditis elegans</i> intestine absorption enterocyte |
| url | https://www.mdpi.com/2072-6643/13/12/4398 |
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