PDF(Pubmed)
Abstract：
In 2017, four independent publications described the glial cell-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) as receptor for the growth differentiation factor 15 (GDF15, also MIC-1, NAG-1) with an expression exclusively in the mice brainstem area postrema (AP) and nucleus tractus solitarii (NTS) where it mediates effects of GDF15 on reduction of food intake and body weight. GDF15 is a cell stress cytokine with a widespread expression and pleiotropic effects, which both seem to be in contrast to the reported highly specialized localization of its receptor. This discrepancy prompts us to re-evaluate the expression pattern of GFRAL in the brain and peripheral tissues of mice. In this detailed immunohistochemical study, we provide evidence for a more widespread distribution of this receptor. Apart from the AP/NTS region, GFRAL-immunoreactivity was found in the prefrontal cortex, hippocampus, nucleus arcuatus and peripheral tissues including liver, small intestine, fat, kidney and muscle tissues. This widespread receptor expression, not taken into consideration so far, may explain the multiple effects of GDF-15 that are not yet assigned to GFRAL. Furthermore, our results could be relevant for the development of novel pharmacological therapies for physical and mental disorders related to body image and food intake, such as eating disorders, cachexia and obesity.
摘要：
2017年，有四个独立的出版物描述了神经胶质细胞衍生的神经营养因子（GDNF）受体α样（GFRAL）作为生长分化因子15（GDF15，还有MIC-1，NAG-1）的受体，仅在小鼠脑干后区（AP）和孤核（NTS）中表达，它介导GDF15对减少食物摄入和体重的作用。GDF15是一种具有广泛表达和多效性的细胞应激细胞因子，两者似乎都与其受体的高度特化定位相反。这种差异促使我们重新评估GFRAL在小鼠脑和外周组织中的表达模式。在这项详细的免疫组织化学研究中，我们提供了这种受体更广泛分布的证据.除AP/NTS区域外，GFRAL-免疫反应性被发现在前额叶皮层，海马体,弓状核和外周组织，包括肝脏，小肠,脂肪，肾脏和肌肉组织.这种广泛的受体表达，到目前为止还没有考虑到，可以解释尚未分配给GFRAL的GDF-15的多重效应。此外，我们的研究结果可能与开发与身体形象和食物摄入相关的身体和精神障碍的新药物疗法有关，比如饮食失调，恶病质和肥胖。
