Bacterial ClpB heat-shock protein, an antigen-mimetic of the anorexigenic peptide α-MSH, at the origin of eating disorders.
Bacterial ClpB heat-shock protein, an antigen-mimetic of the anorexigenic peptide α-MSH, at the origin of eating disorders.
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DOI：
10.1038/tp.2014.98
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发表时间：
2014-10-07
影响因子：
6.8
通讯作者：
Fetissov SO
中科院分区：
文献类型：
--
作者：
Tennoune N;Chan P;Breton J;Legrand R;Chabane YN;Akkermann K;Järv A;Ouelaa W;Takagi K;Ghouzali I;Francois M;Lucas N;Bole-Feysot C;Pestel-Caron M;do Rego JC;Vaudry D;Harro J;Dé E;Déchelotte P;Fetissov SO
进食障碍(EDS)的分子机制目前尚不清楚，包括神经性厌食症(AN)、暴食症和暴饮暴食障碍(BED)。以往的研究表明，免疫球蛋白(Ig)或自身抗体(α-α-msh)与黑素细胞刺激素(Msh)反应，参与调节摄食和情绪，但其来源不明。在这里，我们利用蛋白质组学的方法，将共生肠道细菌大肠杆菌的ClpB热休克解聚伴侣蛋白鉴定为α-msh的构象抗原模拟物。我们发现ClpB免疫的小鼠产生与α-MSH交叉反应的抗ClpB免疫球蛋白，影响进食、体重、焦虑和黑素皮质素受体4信号。此外，慢性灌胃给药可减少小鼠的食物摄入量，并刺激ClpB和α反应性抗体的形成，而缺乏ClpB的大肠杆菌不影响食物摄入量或抗体水平。最后，我们发现与α-MSH交叉反应的抗ClpBIg G水平在AN、暴食症和BED患者中升高，ED患者的ED Inventory-2评分与抗ClpBIg G和Ig M相关，这与我们先前对α-MSH自身抗体的研究结果相似。总之，这项工作表明，细菌ClpB蛋白存在于几种共生和致病微生物中，可能导致与α-MSH交叉反应的自体抗体的产生，与ED患者的饮食和情绪改变有关。我们的数据提示，表达ClpB的肠道微生物可能参与了EDS的病因学。
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.
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影响因子：
3.6
作者：
Hansson, Jenny;Bosco, Nabil;Benyacoub, Jalil
通讯作者：
Benyacoub, Jalil
影响因子：
4.8
作者：
Begriche, Karima;Levasseur, Peter R.;Butler, Andrew A.
通讯作者：
Butler, Andrew A.
DOI：
10.1073/pnas.222658699
发表时间：
2002-12-24
影响因子：
11.1
作者：
Fetissov, SO;Hallman, J;Hökfelt, T
通讯作者：
Hökfelt, T
DOI：
10.1007/978-1-61779-310-3_19
发表时间：
2011-01-01
期刊：
NEUROPEPTIDES: METHODS AND PROTOCOLS
影响因子：
--
作者：
Fetissov, Serguei O.
通讯作者：
Fetissov, Serguei O.
影响因子：
64.8
作者：
Fan, W;Boston, BA;Cone, RD
通讯作者：
Cone, RD