Effects Of High Glucose And Nano - Gold On The Metabolism Of Drosophila Melanogaster And Its Mechanism

The metabolic regulators in drosophila are similar to that of mammals, including SirT, PGC-11a, FOXO, TOR, Akt and nuclear receptors. The studies on metabolic mechanism in drosophila help to further understand the mammalian metabolic regulation. Therefore, investigations of the pathogenesis of type2diabetes using drosophila as a model have been a hotspot in the metabolism field. It has been recently found that ablation of the insulin-producing cells (EPCs) in drosophila causes developmental delay, growth retardation, and elevated carbohydrate levels in larval hemolymph. In addition, disruption of dSH2B decreases insulin-like signaling and somatic growth. dSH2B deficiency also increases hemolymph carbohydrate levels, whole-body lipid levels, lifespan, and resistance to starvation and oxidative stress. Furthermore, the same phenotype have been found in drosophila larvae when fed with high-sucrose diet.In the present study, we found that drosophila on high-sucrose diet developed phenotypes of insulin resistance when examining physiological indexes and the expression levels of genes involved in the insulin pathway. In addition, we screened genes regulated by high-sucrose diet in the fatbody or in the whole larvae via microarray analysis. Our results provide important evidence for investigating the pathogenesis of type2diabetes using drosophila as a model in the future.On the other hand, the development of nanotechnique evokes a debate about the potential hazards of nanomaterials to the human health over the last decade. The mechanisms through which nanoparticles affect physioligical homeostasis in animals remain unknown. Compared with mammals, drosophila show many advantages such as the conservation of major metabolic pathways, the shorter life span and no ethics controversy when used as a model. However, current studies in drosophila mainly focus on the oxidative stress and cell apoptosis, leaving metabolism as a blank. Here we examined the in vivo effects of gold nanoparticles (AuNPs) on metabolism in drosophila larvae. We found that dietary AuNPs entered the fat body, a key metabolic tissue. Larvae fed with AuNPs had increased lipid levels without triggering stress responses. In addition, the PI3K/Akt/mTOR signaling pathway was activated and fatty acid synthesis was increased. Finally, inhibition of mTOR activity abolished such pathophysiological changes. Our data suggest that dietary AuNPs affect lipid metabolism by activating the PI3K/Akt/mTOR pathway.