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Bacterial ClpB heat-shock protein, an antigen-mimetic of the anorexigenic peptide α-MSH, at the origin of eating disorders
The molecular mechanisms at the origin of eating disorders (EDs), including anorexia nervosa (AN), bulimia and binge-eating disorder (BED), are currently unknown. Previous data indicated that immunoglobulins (Igs) or autoantibodies (auto-Abs) reactive with α-melanocyte-stimulating hormone (α-MSH) ar...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350527/ https://www.ncbi.nlm.nih.gov/pubmed/25290265 http://dx.doi.org/10.1038/tp.2014.98 |
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author | Tennoune, N Chan, P Breton, J Legrand, R Chabane, Y N Akkermann, K Järv, A Ouelaa, W Takagi, K Ghouzali, I Francois, M Lucas, N Bole-Feysot, C Pestel-Caron, M do Rego, J-C Vaudry, D Harro, J Dé, E Déchelotte, P Fetissov, S O |
author_facet | Tennoune, N Chan, P Breton, J Legrand, R Chabane, Y N Akkermann, K Järv, A Ouelaa, W Takagi, K Ghouzali, I Francois, M Lucas, N Bole-Feysot, C Pestel-Caron, M do Rego, J-C Vaudry, D Harro, J Dé, E Déchelotte, P Fetissov, S O |
author_sort | Tennoune, N |
collection | PubMed |
description | The molecular mechanisms at the origin of eating disorders (EDs), including anorexia nervosa (AN), bulimia and binge-eating disorder (BED), are currently unknown. Previous data indicated that immunoglobulins (Igs) or autoantibodies (auto-Abs) reactive with α-melanocyte-stimulating hormone (α-MSH) are involved in regulation of feeding and emotion; however, the origin of such auto-Abs is unknown. Here, using proteomics, we identified ClpB heat-shock disaggregation chaperone protein of commensal gut bacteria Escherichia coli as a conformational antigen mimetic of α-MSH. We show that ClpB-immunized mice produce anti-ClpB IgG crossreactive with α-MSH, influencing food intake, body weight, anxiety and melanocortin receptor 4 signaling. Furthermore, chronic intragastric delivery of E. coli in mice decreased food intake and stimulated formation of ClpB- and α-MSH-reactive antibodies, while ClpB-deficient E. coli did not affect food intake or antibody levels. Finally, we show that plasma levels of anti-ClpB IgG crossreactive with α-MSH are increased in patients with AN, bulimia and BED, and that the ED Inventory-2 scores in ED patients correlate with anti-ClpB IgG and IgM, which is similar to our previous findings for α-MSH auto-Abs. In conclusion, this work shows that the bacterial ClpB protein, which is present in several commensal and pathogenic microorganisms, can be responsible for the production of auto-Abs crossreactive with α-MSH, associated with altered feeding and emotion in humans with ED. Our data suggest that ClpB-expressing gut microorganisms might be involved in the etiology of EDs. |
format | Online Article Text |
id | pubmed-4350527 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-43505272015-04-06 Bacterial ClpB heat-shock protein, an antigen-mimetic of the anorexigenic peptide α-MSH, at the origin of eating disorders Tennoune, N Chan, P Breton, J Legrand, R Chabane, Y N Akkermann, K Järv, A Ouelaa, W Takagi, K Ghouzali, I Francois, M Lucas, N Bole-Feysot, C Pestel-Caron, M do Rego, J-C Vaudry, D Harro, J Dé, E Déchelotte, P Fetissov, S O Transl Psychiatry Original Article The molecular mechanisms at the origin of eating disorders (EDs), including anorexia nervosa (AN), bulimia and binge-eating disorder (BED), are currently unknown. Previous data indicated that immunoglobulins (Igs) or autoantibodies (auto-Abs) reactive with α-melanocyte-stimulating hormone (α-MSH) are involved in regulation of feeding and emotion; however, the origin of such auto-Abs is unknown. Here, using proteomics, we identified ClpB heat-shock disaggregation chaperone protein of commensal gut bacteria Escherichia coli as a conformational antigen mimetic of α-MSH. We show that ClpB-immunized mice produce anti-ClpB IgG crossreactive with α-MSH, influencing food intake, body weight, anxiety and melanocortin receptor 4 signaling. Furthermore, chronic intragastric delivery of E. coli in mice decreased food intake and stimulated formation of ClpB- and α-MSH-reactive antibodies, while ClpB-deficient E. coli did not affect food intake or antibody levels. Finally, we show that plasma levels of anti-ClpB IgG crossreactive with α-MSH are increased in patients with AN, bulimia and BED, and that the ED Inventory-2 scores in ED patients correlate with anti-ClpB IgG and IgM, which is similar to our previous findings for α-MSH auto-Abs. In conclusion, this work shows that the bacterial ClpB protein, which is present in several commensal and pathogenic microorganisms, can be responsible for the production of auto-Abs crossreactive with α-MSH, associated with altered feeding and emotion in humans with ED. Our data suggest that ClpB-expressing gut microorganisms might be involved in the etiology of EDs. Nature Publishing Group 2014-10 2014-10-07 /pmc/articles/PMC4350527/ /pubmed/25290265 http://dx.doi.org/10.1038/tp.2014.98 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Original Article Tennoune, N Chan, P Breton, J Legrand, R Chabane, Y N Akkermann, K Järv, A Ouelaa, W Takagi, K Ghouzali, I Francois, M Lucas, N Bole-Feysot, C Pestel-Caron, M do Rego, J-C Vaudry, D Harro, J Dé, E Déchelotte, P Fetissov, S O Bacterial ClpB heat-shock protein, an antigen-mimetic of the anorexigenic peptide α-MSH, at the origin of eating disorders |
title | Bacterial ClpB heat-shock protein, an antigen-mimetic of the anorexigenic peptide α-MSH, at the origin of eating disorders |
title_full | Bacterial ClpB heat-shock protein, an antigen-mimetic of the anorexigenic peptide α-MSH, at the origin of eating disorders |
title_fullStr | Bacterial ClpB heat-shock protein, an antigen-mimetic of the anorexigenic peptide α-MSH, at the origin of eating disorders |
title_full_unstemmed | Bacterial ClpB heat-shock protein, an antigen-mimetic of the anorexigenic peptide α-MSH, at the origin of eating disorders |
title_short | Bacterial ClpB heat-shock protein, an antigen-mimetic of the anorexigenic peptide α-MSH, at the origin of eating disorders |
title_sort | bacterial clpb heat-shock protein, an antigen-mimetic of the anorexigenic peptide α-msh, at the origin of eating disorders |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350527/ https://www.ncbi.nlm.nih.gov/pubmed/25290265 http://dx.doi.org/10.1038/tp.2014.98 |
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