Fetissov Sergueï O, Lucas Nicolas, Legrand Romain
INSERM UMR1073, Nutrition, Gut and Brain Laboratory, Rouen, France; Institute for Research and Innovation in Biomedicine (IRIB), University of Rouen Normandy, Rouen, France.
Front Endocrinol (Lausanne). 2017 Jan 27;8:10. doi: 10.3389/fendo.2017.00010. eCollection 2017.
Part of circulating ghrelin is bound to immunoglobulins (Ig) protecting it from degradation and preserving its functional activity. This review summarizes the data on ghrelin- and desacyl-ghrelin-reactive IgG in conditions of altered appetite and energy balance. Plasma levels and affinity kinetics of such IgG were compared in patients with obesity and anorexia nervosa (AN) and in animal models of obesity including mice, high-fat diet-induced obese mice, and obese Zucker rats as well as in mice after chronic food restriction and activity-based anorexia and in rats with methotrexate-induced anorexia. We show that plasmatic IgG in both obese humans and animals are characterized by increased affinity for ghrelin. In contrast, patients with AN and anorectic rodents all show lower affinity of ghrelin- and desacyl-ghrelin-reactive IgG, respectively, the changes which were not observed in non-anorectic, chronically starved mice. We also show that affinity of ghrelin-reactive IgG correlate with plasma levels of ghrelin. These data point to common mechanisms underlying modifications of affinity kinetics properties of ghrelin-reactive IgG during chronic alterations of energy balance in humans and rodents and support a functional role of such autoantibodies in ghrelin-mediated regulation of appetite.
循环中的胃饥饿素一部分与免疫球蛋白（Ig）结合，从而免受降解并保持其功能活性。本综述总结了在食欲和能量平衡改变的情况下，胃饥饿素和去酰基胃饥饿素反应性IgG的数据。比较了肥胖症和神经性厌食症（AN）患者以及肥胖动物模型（包括小鼠、高脂饮食诱导的肥胖小鼠和肥胖Zucker大鼠）、慢性食物限制和基于活动的厌食症后的小鼠以及甲氨蝶呤诱导的厌食症大鼠中此类IgG的血浆水平和亲和力动力学。我们发现，肥胖的人类和动物体内的血浆IgG对胃饥饿素的亲和力均增加。相比之下，AN患者和厌食性啮齿动物分别显示出胃饥饿素和去酰基胃饥饿素反应性IgG的亲和力较低，而在非厌食性、长期饥饿的小鼠中未观察到这种变化。我们还表明，胃饥饿素反应性IgG的亲和力与胃饥饿素的血浆水平相关。这些数据表明，在人类和啮齿动物能量平衡的慢性改变过程中，胃饥饿素反应性IgG亲和力动力学特性改变的潜在共同机制，并支持此类自身抗体在胃饥饿素介导的食欲调节中的功能作用。
