Abstract

The crosstalk between haemocytes and fat body throught Upd3/Dome pathway mediate the pro-inflammatory response in high-sugar-fed larvae in Drosophila melanogaster. Sebastián Díaz1, Fernanda Lourido1, Mauricio Gonzales2,3, Verónica Cambiazo2,3, Nicolás Tobar1,2 Cellular Biology Laboratory1, Bioinformatics and Genetic Expression Laboratory2, INTA-Universidad de Chile and Fondap Center CGR3 Introduction: The diseases associated with hypercaloric diet 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 that involves the JAK/STAT pathway, is mediated in D. melanogaster by a family of cytokines called Unpaired and its only receptor, Domeless. Upd3 is produced as a result of an immune challenge and has been related to the alteration of the metabolism induced by the diet. Methods: The flies were fed normal and high in sugar (HSD diet). In order to study the role of Upd3/Dome axis in the pro-inflammatory responses induced by HSD, we used the GAL4/UAS system to knock-down both proteins in Drosophila larvae. Survival curves for flies fed both diets were evaluated. The number of haemocytes, the activation of Upd3/Dome pathway and the expression of inflammatory markers were determined by cell counting, immunofluorescence and qPCR assays, respectively. Results: The flies fed with HSD show a delay in the development and a reduction of the survival. In addition, an increase in the number of circulating haemocytes was observed. On the other hand, the inhibition of the expression of upd3 and its receptor, in haemocytes and fat body, respectively, was capable of revert the inflammatory phenotype, prolonging the lifespan. Conclusions: These results show that larvae fed on HSD present an abnormal activation of the innate immune system and suggest that the Upd3/Dome crosstalk between haemocytes and fat body would mediate the inflammatory response associated with hypercaloric diets. Supported by FONDECYT POSTDOCTORADO #3160626 and PAI77170001