Abstract

High sugar diet stimulates the pro-inflammatory response mediated by hemocytes and fatty body, which favors the metastatic capacity of tumors generated in larvae of Drosophila melanogaster. Nicolás Tobar1, Fernanda Lourido1, Sebastián Díaz1, Verónica Cambiazo2,3 Cellular Biology Laboratory1, Bioinformatics and Genetic Expression Laboratory2, INTA-Universidad de Chile and Fondap Center CGR3 Introduction. Currently, there is a consensus that external factors, such as diet, play a decisive role in the development of different forms of cancer. It has been shown that the condition of hyperglycemia, secondary to insulin resistance and obesity, is a recognized risk factor in human carcinogenesis. On the other hand, diseases such as obesity and type 2 diabetes share general characteristics that include alterations in homeostasis and activation of the innate immune system due to inflammatory conditions. The inflammatory response involving the JAK/STAT pathway is mediated in D. melanogaster by a family of cytokines called Unpared (Upd), whose only receptor is Domeless (Dome). Methods: The flies were fed a normal diet or high sugar diet (HSD). To study the role of the Upd3/Dome axis in the proinflammatory responses induced by HSD, we inhibited the expression of both proteins in D. melanogaster larvae. On the other hand, the generation of tumors in eye imaginal discs was induced by the overexpression of RASV12 and the elimination of scrib using the MARCM system. Results: The flies fed with HSD showed an increase in the number of circulating hemocytes and an activation of the JAK/STAT pathway. Additionally, HSD favored the development of tumors and caused an increase in the number and size of metastatic foci. Conclusions: These results show that the larvae of D. melanogaster fed with HSD present an abnormal activation of the innate immune system and suggest that the inflammatory response associated with the hypercaloric diets could be able to promote the metastatic behavior of the tumors. Supported by FONDECYT, project PAI77170001