Insect Biomedical Research Center, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto, Japan.
Eur Rev Med Pharmacol Sci. 2019 Jan;23(2):857-876. doi: 10.26355/eurrev_201901_16901.
High-fat diet (HFD) feeding stimulates fat accumulation in mammals and Drosophila. In the present study, we examined whether simultaneous feeding of familiar anti-obesity drugs, quercetin glycosides (QG) and epigallocatechin gallate (EGCG), to Drosophila has the same suppressive effect on fat accumulation as previously reported in rats and mice. To understand the underlying molecular mechanisms of HFD diet-induced obesity and the suppression effect of the drugs, we performed transcriptome analyses.
We induced extra fat accumulation by feeding Drosophila fly food containing 20% coconut oil and quantified the triglyceride accumulated in flies. The effects of anti-obesity drugs were also evaluated. We isolated total RNA from each sample and performed RNA-seq analyses and quantitive Real Time-Polymerase Chain Reaction (qRT-PCR) to investigate altered gene expression.
The mRNA levels of several genes involved in lipid metabolism, glycolysis/gluconeogenesis, and anti-oxidative stress changed in HFD-fed adults. Moreover, the levels altered in those fed an HFD with QG or EGCG. The qRT-PCR further confirmed the RNA-seq data, suggesting that the expression of five essential genes for lipid metabolism changed in HFD-fed flies and altered in the flies treated with anti-obesity drugs. The most remarkable alteration was observed in the dHSL gene encoding a lipase involved in lipid-storage after HFD feeding and HFD with QG or EGCG. These alterations are consistent with HFD-induced fat accumulation as well as the anti-obesity effects of the drugs in mammals, suggesting that the genes play an important role in anti-obesity effects.
These are the first reports to date of entire profiles of altered gene expression under the conditions of diet-induced obesity and its suppression by anti-obesity drugs in Drosophila.
高脂肪饮食（HFD）喂养会刺激哺乳动物和果蝇体内脂肪堆积。本研究旨在检验同时喂食熟悉的抗肥胖药物槲皮素糖苷（QG）和表没食子儿茶素没食子酸酯（EGCG）是否对果蝇脂肪堆积产生与先前在大鼠和小鼠中报道的相同的抑制作用。为了了解 HFD 饮食诱导肥胖的潜在分子机制和药物的抑制作用，我们进行了转录组分析。
我们通过喂食含有 20%椰子油的果蝇食物来诱导额外的脂肪堆积，并对果蝇体内积累的甘油三酯进行定量。还评估了抗肥胖药物的效果。我们从每个样本中分离总 RNA，并进行 RNA-seq 分析和定量实时聚合酶链反应（qRT-PCR），以研究基因表达的变化。
HFD 喂养的成年果蝇中，参与脂质代谢、糖酵解/糖异生和抗氧化应激的几个基因的 mRNA 水平发生了变化。此外，在喂食 HFD 加 QG 或 EGCG 的果蝇中，这些基因的水平也发生了改变。qRT-PCR 进一步证实了 RNA-seq 数据，表明 HFD 喂养的果蝇中 5 个脂质代谢关键基因的表达发生了改变，而在喂食抗肥胖药物的果蝇中则发生了改变。最显著的改变发生在编码脂肪酶的 dHSL 基因上，该基因参与了 HFD 喂养后脂肪的储存以及 HFD 加 QG 或 EGCG 的作用。这些改变与 HFD 诱导的脂肪堆积以及药物在哺乳动物中的抗肥胖作用一致，表明这些基因在抗肥胖作用中发挥着重要作用。
这是迄今为止首次在果蝇中报道在饮食诱导肥胖及其通过抗肥胖药物抑制的条件下基因表达的全谱变化。
