果蝇细胞因子Unpaired2通过远端控制胰岛素分泌调节生理平衡

来源：仪方生物 www.yeslab.com

果蝇体内脂肪体（fat body：FB）类似脊椎动物体内的脂肪组织的功能，是果蝇转换营养状态至胰岛素生产细胞（IPCs）的感受器，从而分泌果蝇胰岛素样肽（Dilps）。Dilps分泌进而调节能量平衡并促进机体生长。我们鉴定出不配对2（Unpaired2：Upd2），一种I型细胞因子，作为一个进食状态下产生的一个因子。一旦Upd2功能受到干扰，就会影响生长和能量代谢。在GABAergic神经细胞中Upd2激活JAK/STAT信号，影响到IPCs。这个活化能够缓解IPCs中GABAergic神经细胞的抑制状态，从而影响Dilips的分泌。我们发现人瘦素能补救upd2突变表型，提示Upd2是一个瘦素同工物。


Drosophila Cytokine Unpaired 2 Regulates Physiological Homeostasis by Remotely Controlling Insulin Secretion

Akhila Rajan1,* and Norbert Perrimon1,2,*

SUMMARY
In Drosophila, the fat body (FB), a functional analog of the vertebrate adipose tissue, is the nutrient sensor that conveys the nutrient status to the insulin-producing cells (IPCs) in the fly brain to release Drosophila insulin-like peptides (Dilps). Dilp secretion in turn regulates energy balance and promotes systemic growth. We identify Unpaired 2 (Upd2), a protein with similarities to type I cytokines, as a secreted factor produced by the FB in the fed state. When upd2 function is perturbed specifically in the FB, it results in a systemic reduction in growth and alters energy metabolism. Upd2 activates JAK/ STAT signaling in a population of GABAergic neurons that project onto the IPCs. This activation relieves the inhibitory tone of the GABAergic neurons on the IPCs, resulting in the secretion of Dilps. Strikingly, we find that human Leptin can rescue the upd2 mutant phenotypes, suggesting that Upd2 is the functional homolog of Leptin.