Growth-Blocking Peptides As Nutrition-Sensitive Signals for Insulin Secretion and Body Size Regulation.
Growth-Blocking Peptides As Nutrition-Sensitive Signals for Insulin Secretion and Body Size Regulation.
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DOI：
10.1371/journal.pbio.1002392
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发表时间：
2016-02
期刊：
影响因子：
9.8
通讯作者：
Mirth CK
中科院分区：
文献类型：
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作者：
Koyama T;Mirth CK
在果蝇中，脂肪体在功能上等同于哺乳动物的肝脏和脂肪细胞，在调节系统生长以响应营养方面起着核心作用。脂肪体通过雷帕霉素靶（TOR）信号传导感知细胞内氨基酸，并产生一种未鉴定的体液因子来调节胰岛素样肽（ILP）在胰岛素产生细胞中的合成和/或分泌。在这里，我们发现两种肽，生长阻断肽（GBP 1）和CG 11395（GBP 2），是在脂肪体中产生的，以响应氨基酸和TOR信号。降低脂肪体中GBP 1和GBP 2（GBP）的表达，由于生长速率降低，导致体型变小。此外，我们发现GBP直接或间接地刺激胰岛素产生细胞分泌ILP，从而增加全身胰岛素和胰岛素样生长因子信号传导活性。我们的发现填补了我们对脂肪体如何将营养信息传递给胰岛素产生细胞以控制体型的理解中的一个重要空白。昆虫脂肪体通过响应膳食氨基酸产生和分泌两种肽GBP 1和GBP 2来传递营养信息以控制身体生长。这两种肽刺激胰岛素样肽分泌，增加全身胰岛素信号活性并诱导全身生长。生物体根据环境条件调整其发育，以最大限度地发挥重要的生活史特征，如身体大小和生存。通过对果蝇（Drosophila melanogaster）的研究，我们开始解决环境条件（特别是营养）改变发育过程的一些分子机制。昆虫脂肪体在功能上等同于哺乳动物肝脏和脂肪细胞。作为对食物氨基酸浓度的反应，脂肪体分泌肽信号进入昆虫血流，调节重要的生长调节肽（胰岛素样肽）的系统释放。这种肽信号的性质以前是未知的。在这里，我们发现两种肽，生长阻断肽（GBP 1）和CG 11395（GBP 2），是在脂肪体中产生的氨基酸。一旦从脂肪体分泌，这两种肽刺激胰岛素样肽的分泌，这导致身体其余部分的胰岛素信号传导活性升高，以刺激身体生长。
In Drosophila, the fat body, functionally equivalent to the mammalian liver and adipocytes, plays a central role in regulating systemic growth in response to nutrition. The fat body senses intracellular amino acids through Target of Rapamycin (TOR) signaling, and produces an unidentified humoral factor(s) to regulate insulin-like peptide (ILP) synthesis and/or secretion in the insulin-producing cells. Here, we find that two peptides, Growth-Blocking Peptide (GBP1) and CG11395 (GBP2), are produced in the fat body in response to amino acids and TOR signaling. Reducing the expression of GBP1 and GBP2 (GBPs) specifically in the fat body results in smaller body size due to reduced growth rate. In addition, we found that GBPs stimulate ILP secretion from the insulin-producing cells, either directly or indirectly, thereby increasing insulin and insulin-like growth factor signaling activity throughout the body. Our findings fill an important gap in our understanding of how the fat body transmits nutritional information to the insulin producing cells to control body size. The insect fat body transmits nutritional information to control body growth by producing and secreting two peptides, GBP1 and GBP2, in response to dietary amino acids. These two peptides stimulate insulin-like peptide secretion, increasing insulin-signaling activity throughout the body and inducing systemic growth. Organisms adjust their development in response to environmental conditions to maximize important life history traits such as body size and survival. From work in the fruit fly, Drosophila melanogaster, we are beginning to resolve some of the molecular mechanisms through which environmental conditions, specifically nutrition, modify developmental processes. The insect fat body is functionally equivalent to the mammalian liver and adipocytes. In response to the concentration of dietary amino acids, the fat body secretes a peptide signal into the insect bloodstream that regulates the systemic release of important growth-regulating peptides, the insulin-like peptides. The nature of this peptide signal was previously unknown. Here we found that two peptides, Growth-Blocking Peptide (GBP1) and CG11395 (GBP2), are produced in the fat body in response to amino acids. Once secreted from the fat body, these two peptides stimulate secretion of insulin-like peptides, which results in elevating insulin-signaling activity in the rest of the body to stimulate body growth.