Anti-ghrelin immunoglobulins modulate ghrelin stability and its orexigenic effect in obese mice and humans.

Anti-ghrelin immunoglobulins modulate ghrelin stability and its orexigenic effect in obese mice and humans.
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DOI:
10.1038/ncomms3685
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发表时间:
2013
影响因子:
16.6
通讯作者:
Fetissov, Serguei O.
Fetissov, Serguei O.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Takagi, Kuniko;Legrand, Romain;Asakawa, Akihiro;Amitani, Haruka;Francois, Marie;Tennoune, Naouel;Coeffier, Moise;Claeyssens, Sophie;do Rego, Jean-Claude;Dechelotte, Pierre;Inui, Akio;Fetissov, Serguei O.

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肥胖的个体通常食欲增加,尽管主要的促食欲激素生长素释放肽的血浆水平正常。在这里,我们表明,生长素释放肽在血浆中的降解抑制生长素释放肽反应性IgG免疫球蛋白,显示增加的结合亲和力,生长素释放肽在肥胖患者和小鼠。胃饥饿素与来自肥胖个体的IgG(但不与来自厌食症或对照患者的IgG)一起共同施用增加大鼠的食物摄入。类似地,长期注射生长素释放肽和来自ob/ob小鼠的IgG增加小鼠的食物摄入、进餐频率和总瘦体重。这些数据表明,在肥胖的人类和小鼠中,与胃饥饿素亲和力增加的IgG增强了胃饥饿素的促食欲作用,这可能导致食欲增加和暴饮暴食。 肥胖通常与食欲和食物摄入量增加有关,尽管饥饿激素ghrelin的血液水平正常。作者在这里指出,肥胖小鼠和人类血液中的生长素释放肽反应性抗体通过保护生长素释放肽不被降解而增强其促食欲作用。
Obese individuals often have increased appetite despite normal plasma levels of the main orexigenic hormone ghrelin. Here we show that ghrelin degradation in the plasma is inhibited by ghrelin-reactive IgG immunoglobulins, which display increased binding affinity to ghrelin in obese patients and mice. Co-administration of ghrelin together with IgG from obese individuals, but not with IgG from anorectic or control patients, increases food intake in rats. Similarly, chronic injections of ghrelin together with IgG from ob/ob mice increase food intake, meal frequency and total lean body mass of mice. These data reveal that in both obese humans and mice, IgG with increased affinity for ghrelin enhances ghrelin’s orexigenic effect, which may contribute to increased appetite and overeating. Obesity is often associated with increased appetite and food intake, despite normal blood levels of the hunger hormone ghrelin. Here the authors show that ghrelin-reactive antibodies in the blood of obese mice and humans enhance the orexigenic effect of ghrelin by protecting it from degradation.
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