Global Health Institute, School of Life Science, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Global Health Institute, School of Life Science, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Cell Rep. 2019 Apr 16;27(3):886-899.e6. doi: 10.1016/j.celrep.2019.03.074.
In ectotherms, increased ambient temperature requires the organism to consume substantial amounts of energy to sustain a higher metabolic rate, prevent cellular damage, and respond to heat stress. Here, we identify a heat-inducible apolipoprotein required for thermal acclimation in Drosophila. Neuropeptide-like precursor 2 (Nplp2) is an abundant hemolymphatic protein thought to be a neuropeptide. In contrast, we show that Nplp2 contributes to lipid transport, functioning as an exchangeable apolipoprotein. More precisely, Nplp2-deficient flies accumulate lipids in their gut, have reduced fat stores, and display a dyslipoproteinemia, showing that Nplp2 is required for dietary lipid assimilation. Importantly, Nplp2 is induced upon thermal stress and contributes to survival upon heat stress. We propose that Nplp2 associates with lipoprotein particles under homeostatic and high energy-demand conditions to optimize fat transport and storage. Our study also shows that modulation of the lipid uptake and transport machinery is part of an integrated cytoprotective response.
在变温动物中，环境温度的升高要求生物消耗大量的能量来维持更高的代谢率，防止细胞损伤，并应对热应激。在这里，我们鉴定了一种在果蝇中适应热的热诱导载脂蛋白。神经肽样前体 2 (Nplp2) 是一种丰富的血淋巴蛋白，被认为是一种神经肽。相比之下，我们发现 Nplp2 有助于脂质转运，作为一种可交换的载脂蛋白发挥作用。更准确地说，Nplp2 缺陷的果蝇在肠道中积累脂质，脂肪储存减少，并表现出脂蛋白血症，表明 Nplp2 是膳食脂质吸收所必需的。重要的是，Nplp2 在热应激时被诱导，并有助于热应激时的存活。我们提出，Nplp2 在稳态和高能量需求条件下与脂蛋白颗粒结合，以优化脂肪运输和储存。我们的研究还表明，脂质摄取和转运机制的调节是细胞保护反应的一部分。
