RNA-seq analysis of diet-driven obesity and anti-obesity effects of quercetin glucoside or epigallocatechin gallate in Drosophila adults

M. Azuma, T. Dat Le, Y. Yoshimoto, N. Hiraki, M. Yamanaka, F. Omura, Y.H. Inoue

Insect Biomedical Research Center, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto, Japan. yhinoue@kit.ac.jp

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• Pharmacology

OBJECTIVE: 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.

MATERIALS AND METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

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