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Bacterial ClpB heat-shock protein, an antigen-mimetic of the anorexigenic peptide ?-MSH, at the origin of eating disorders.


ABSTRACT: 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 ?-melanocyte-stimulating hormone (?-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 ?-MSH. We show that ClpB-immunized mice produce anti-ClpB IgG crossreactive with ?-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 ?-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 ?-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 ?-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 ?-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.

SUBMITTER: Tennoune N 

PROVIDER: S-EPMC4350527 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Bacterial ClpB heat-shock protein, an antigen-mimetic of the anorexigenic peptide α-MSH, at the origin of eating disorders.

Tennoune N N   Chan P P   Breton J J   Legrand R R   Chabane Y N YN   Akkermann K K   Järv A A   Ouelaa W W   Takagi K K   Ghouzali I I   Francois M M   Lucas N N   Bole-Feysot C C   Pestel-Caron M M   do Rego J-C JC   Vaudry D D   Harro J J   Dé E E   Déchelotte P P   Fetissov S O SO  

Translational psychiatry 20141007


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 gu  ...[more]

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