Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
PLoS Genet. 2012;8(7):e1002828. doi: 10.1371/journal.pgen.1002828. Epub 2012 Jul 26.
Interorgan lipid transport occurs via lipoproteins, and altered lipoprotein levels correlate with metabolic disease. However, precisely how lipoproteins affect tissue lipid composition has not been comprehensively analyzed. Here, we identify the major lipoproteins of Drosophila melanogaster and use genetics and mass spectrometry to study their assembly, interorgan trafficking, and influence on tissue lipids. The apoB-family lipoprotein Lipophorin (Lpp) is the major hemolymph lipid carrier. It is produced as a phospholipid-rich particle by the fat body, and its secretion requires Microsomal Triglyceride Transfer Protein (MTP). Lpp acquires sterols and most diacylglycerol (DAG) at the gut via Lipid Transfer Particle (LTP), another fat body-derived apoB-family lipoprotein. The gut, like the fat body, is a lipogenic organ, incorporating both de novo-synthesized and dietary fatty acids into DAG for export. We identify distinct requirements for LTP and Lpp-dependent lipid mobilization in contributing to the neutral and polar lipid composition of the brain and wing imaginal disc. These studies define major routes of interorgan lipid transport in Drosophila and uncover surprising tissue-specific differences in lipoprotein lipid utilization.
器官间的脂质运输是通过脂蛋白进行的，而脂蛋白水平的改变与代谢性疾病相关。然而，脂蛋白如何影响组织脂质组成尚未得到全面分析。在这里，我们鉴定了黑腹果蝇的主要脂蛋白，并利用遗传学和质谱技术研究了它们的组装、器官间运输以及对组织脂质的影响。载脂蛋白 B 家族脂蛋白 Lipophorin (Lpp) 是主要的血液脂质载体。它由脂肪体以富含磷脂的颗粒形式产生，其分泌需要微体甘油三酯转移蛋白 (MTP)。Lpp 通过另一种脂肪体衍生的载脂蛋白 B 家族脂蛋白脂滴转移蛋白 (LTP) 在肠道中获得固醇和大多数二酰基甘油 (DAG)。肠道和脂肪体一样，是一个合成脂质的器官，将从头合成和膳食脂肪酸掺入 DAG 中以进行输出。我们确定了 LTP 和 Lpp 依赖性脂质动员在贡献大脑和翅膀 imaginal 盘中性和极性脂质组成方面的不同要求。这些研究定义了果蝇中器官间脂质运输的主要途径，并揭示了脂蛋白脂质利用的惊人的组织特异性差异。
