Kolasa Annabella M, Bhogal Jasleen K, DiAngelo Justin R
Division of Science, Penn State Berks, Reading, PA, USA.
Biochem Biophys Rep. 2021 Jan 23;25:100919. doi: 10.1016/j.bbrep.2021.100919. eCollection 2021 Mar.
The availability of excess nutrients in Western diets has led to the overaccumulation of these nutrients as triglycerides, a condition known as obesity. The full complement of genes important for regulating triglyceride storage is not completely understood. Genome-wide RNAi screens in cells have identified genes involved in mRNA splicing as important lipid storage regulators. Our lab has shown that a group of splicing factors called heterogeneous nuclear ribonucleoproteins (hnRNPs) regulate lipid metabolism in the fly fat body; however, the identities of all the hnRNPs that function to control triglyceride storage are not known. Here, we used the GAL4/UAS system to induce RNAi to the hnRNP () in the fat body to assess whether this hnRNP has any metabolic functions. Decreasing levels resulted in less triglycerides being stored throughout the fly. Interestingly, decreasing fat body expression resulted in increased triglyceride storage in the fat body, but blunted triglyceride storage in non-fat body tissues, suggesting a defect in lipid transport. Consistent with this hypothesis, the expression of (), (), and (), apolipoprotein genes important for lipid transport through the fly hemolymph, was decreased in -RNAi flies, suggesting that regulates the transport of lipids from the fly fat body to surrounding tissues. Together, these results indicate that plays a role in controlling lipid transport and storage and provide additional evidence of the link between gene expression and the regulation of lipid metabolism.
西方饮食中过量营养素的存在导致这些营养素以甘油三酯的形式过度积累,这种情况被称为肥胖。对于调节甘油三酯储存重要的完整基因组合尚未完全了解。在细胞中进行的全基因组RNA干扰筛选已经确定参与mRNA剪接的基因是重要的脂质储存调节因子。我们实验室已经表明,一组称为异质核糖核蛋白(hnRNPs)的剪接因子在果蝇脂肪体中调节脂质代谢;然而,所有发挥控制甘油三酯储存功能的hnRNPs的身份尚不清楚。在这里,我们使用GAL4/UAS系统在果蝇脂肪体中诱导对hnRNP()的RNA干扰,以评估这种hnRNP是否具有任何代谢功能。降低()水平导致果蝇全身储存的甘油三酯减少。有趣的是,降低脂肪体中()的表达导致脂肪体中甘油三酯储存增加,但非脂肪体组织中的甘油三酯储存受到抑制,这表明脂质运输存在缺陷。与这一假设一致,在()-RNA干扰果蝇中,对于通过果蝇血淋巴进行脂质运输重要的载脂蛋白基因()、()和()的表达降低,这表明()调节从果蝇脂肪体到周围组织的脂质运输。总之,这些结果表明()在控制脂质运输和储存中起作用,并为基因表达与脂质代谢调节之间的联系提供了额外的证据。