Université Nice Sophia Antipolis, CNRS, Inserm, iBV, 06100 Nice, France.
Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland.
Cell Metab. 2016 Apr 12;23(4):675-84. doi: 10.1016/j.cmet.2016.03.003.
Adaptation of organisms to ever-changing nutritional environments relies on sensor tissues and systemic signals. Identification of these signals would help understand the physiological crosstalk between organs contributing to growth and metabolic homeostasis. Here we show that Eiger, the Drosophila TNF-α, is a metabolic hormone that mediates nutrient response by remotely acting on insulin-producing cells (IPCs). In the condition of nutrient shortage, a metalloprotease of the TNF-α converting enzyme (TACE) family is active in fat body (adipose-like) cells, allowing the cleavage and release of adipose Eiger in the hemolymph. In the brain IPCs, Eiger activates its receptor Grindelwald, leading to JNK-dependent inhibition of insulin production. Therefore, we have identified a humoral connexion between the fat body and the brain insulin-producing cells relying on TNF-α that mediates adaptive response to nutrient deprivation.
生物体对不断变化的营养环境的适应依赖于感应组织和全身信号。识别这些信号将有助于了解器官间促进生长和代谢平衡的生理串扰。在这里，我们表明果蝇 TNF-α 的 Eiger 是一种代谢激素，通过远程作用于胰岛素生成细胞 (IPCs) 来介导营养反应。在营养缺乏的情况下，TNF-α 转化酶 (TACE) 家族的金属蛋白酶在脂肪体（脂肪样）细胞中活跃，允许脂肪 Eiger 在血淋巴中裂解和释放。在脑中的 IPCs 中，Eiger 激活其受体 Grindelwald，导致 JNK 依赖性胰岛素生成抑制。因此，我们已经确定了一种依赖于 TNF-α 的脂肪体和脑胰岛素生成细胞之间的体液连接，它介导了对营养缺乏的适应性反应。
