Drosophila PDGF/VEGF signaling from muscles to hepatocyte-like cells protects against obesity.
Drosophila PDGF/VEGF signaling from muscles to hepatocyte-like cells protects against obesity.
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DOI：
10.7554/elife.56969
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发表时间：
2020-10-27
期刊：
影响因子：
7.7
通讯作者：
Perrimon N
中科院分区：
文献类型：
--
作者：
Ghosh AC;Tattikota SG;Liu Y;Comjean A;Hu Y;Barrera V;Ho Sui SJ;Perrimon N
PDGF/VEGF配体通过自分泌、旁分泌和内分泌机制调节多细胞生物体中的多种生物学过程。我们研究了果蝇PDGF/VEGF样因子（Pvfs）的器官特异性代谢作用。我们将联合收割机遗传学方法和单核测序相结合，证明肌源性Pvf 1通过激活卵母细胞中的Pi 3 K/Akt 1/TOR信号级联，向果蝇肝细胞样细胞/卵母细胞发出信号，从而抑制脂质合成。在功能上，这个信号轴调节新羽化的果蝇脂肪组织脂质储存的扩张。苍蝇化蛹后出现有限的脂肪组织脂质储存和脂质水平逐步积累通过脂质合成。我们发现，成人肌肉特异性表达的pvf 1迅速增加，在这个阶段，肌肉到卵母细胞Pvf 1信号抑制脂肪组织脂质储存的扩张的过程中达到完成。我们的研究结果提供了第一个证据，在一个后生动物的PDGF/VEGF配体作为一种肌因子，调节全身脂质稳态激活TOR肝细胞样细胞。
PDGF/VEGF ligands regulate a plethora of biological processes in multicellular organisms via autocrine, paracrine, and endocrine mechanisms. We investigated organ-specific metabolic roles of Drosophila PDGF/VEGF-like factors (Pvfs). We combine genetic approaches and single-nuclei sequencing to demonstrate that muscle-derived Pvf1 signals to the Drosophila hepatocyte-like cells/oenocytes to suppress lipid synthesis by activating the Pi3K/Akt1/TOR signaling cascade in the oenocytes. Functionally, this signaling axis regulates expansion of adipose tissue lipid stores in newly eclosed flies. Flies emerge after pupation with limited adipose tissue lipid stores and lipid level is progressively accumulated via lipid synthesis. We find that adult muscle-specific expression of pvf1 increases rapidly during this stage and that muscle-to-oenocyte Pvf1 signaling inhibits expansion of adipose tissue lipid stores as the process reaches completion. Our findings provide the first evidence in a metazoan of a PDGF/VEGF ligand acting as a myokine that regulates systemic lipid homeostasis by activating TOR in hepatocyte-like cells.