A glucagon-like endocrine pathway in Drosophila modulates both lipid and carbohydrate homeostasis.
A glucagon-like endocrine pathway in Drosophila modulates both lipid and carbohydrate homeostasis.
复制标题
DOI：
10.1242/jeb.016451
复制
发表时间：
2008-10
期刊：
影响因子：
--
通讯作者：
Zipursky SL
中科院分区：
文献类型：
--
作者：
Bharucha KN;Tarr P;Zipursky SL
能量平衡的调节是所有生物体的基础。果蝇脂肪体是甘油三酯和糖原的储存库，分别结合了哺乳动物脂肪组织和肝脏组织的能量储存功能。在这里，我们发现果蝇脂肪动力学激素受体（AKHR）的突变，一种哺乳动物胰高血糖素受体的功能类似物，导致脂质和碳水化合物的异常积累。由于其肥胖表型，AKHR突变体具有明显的饥饿抗性。我们发现，AKHR在脂肪体中表达，有趣的是，在介导甜味的味觉神经元子集中表达。遗传拯救实验证实代谢表型完全由脂肪体AKHR表达引起。行为实验表明，AKHR突变体既不久坐也不贪食，这表明代谢异常源于保留能量储存的遗传倾向。综上所述，我们的研究结果表明，在果蝇脂肪体中，单一的内分泌途径有助于脂质和碳水化合物的分解代谢。
The regulation of energy homeostasis is fundamental to all organisms. The Drosophila fat body serves as a repository for both triglycerides and glycogen, combining the energy storage functions of mammalian adipose and hepatic tissues, respectively. Here we show that mutation of the Drosophila adipokinetic hormone receptor (AKHR), a functional analog of the mammalian glucagon receptor, leads to abnormal accumulation of both lipid and carbohydrate. As a consequence of their obese phenotypes, AKHR mutants are markedly starvation resistant. We show that AKHR is expressed in the fat body, and, intriguingly, in a subset of gustatory neurons that mediate sweet taste. Genetic rescue experiments establish that the metabolic phenotypes arise exclusively from the fat body AKHR expression. Behavioral experiments demonstrate that AKHR mutants are neither sedentary nor hyperphagic, suggesting the metabolic abnormalities derive from a genetic propensity to retain energy stores. Taken together, our results indicate that a single endocrine pathway contributes to both lipid and carbohydrate catabolism in the Drosophila fat body.