Identification of Modulators of the <i>C.</i> <i>elegans</i> Aryl Hydrocarbon Receptor and Characterization of Transcriptomic and Metabolic AhR-1 Profiles

• Published in: Antioxidants
• Main Authors: Lucie Larigot, Linh-Chi Bui, Marine de Bouvier, Ophélie Pierre, Grégory Pinon, Justine Fiocca, Mohammad Ozeir, Cendrine Tourette, Chris Ottolenghi, Sandrine Imbeaud, Clément Pontoizeau, Benjamin J. Blaise, Aline Chevallier, Céline Tomkiewicz, Béatrice Legrand, Bénédicte Elena-Herrmann, Christian Néri, Vanessa Brinkmann, Pierre Nioche, Robert Barouki, Natascia Ventura, Julien Dairou, Xavier Coumoul
• Format: Article
• Language: English
• Published: MDPI AG 2022-05-01
• Subjects: Aryl hydrocarbon Receptor; <i>Caenorhabditis elegans</i>; transcriptomics; metabolomics; modulators
• Online Access: https://www.mdpi.com/2076-3921/11/5/1030
• ISSN: 2076-3921

The Aryl hydrocarbon Receptor (AhR) is a xenobiotic sensor in vertebrates, regulating the metabolism of its own ligands. However, no ligand has been identified to date for any AhR in invertebrates. In <i>C.</i> <i>elegans</i>, the AhR ortholog, AHR-1, displays physiological functions. Therefore, we compared the transcriptomic and metabolic profiles of worms expressing AHR-1 or not and investigated the putative panel of chemical AHR-1 modulators. The metabolomic profiling indicated a role for AHR-1 in amino acids, carbohydrates, and fatty acids metabolism. The transcriptional profiling in neurons expressing AHR-1, identified 95 down-regulated genes and 76 up-regulated genes associated with neuronal and metabolic functions in the nervous system. A gene reporter system allowed us to identify several AHR-1 modulators including bacterial, dietary, or environmental compounds. These results shed new light on the biological functions of AHR-1 in <i>C.</i> <i>elegans</i> and perspectives on the evolution of the AhR functions across species.