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We report that flies with a deletion of dSTING are <a href="http://sci-hub.hk/10.1039/c0md00194e">buy Camicinal</a> sensitive to the starvation and oxidative stress.Detailed analysis reveals that dSTING deletion results in a significant decrease in the main storage metabolites, such as TAG, trehalose, and glycogen.Moreover, we also found that FASN and ACC <a href="https://www.targetmol.com/compound/Camicinal">buy Camicinal</a> interacted with each other, indicating that all three proteins might be components of a large complex.Importantly, dSTING deletion leads to the decreased FASN activity and defects in ACC cellular localization suggesting a direct role of dSTING in lipid metabolism of fruit flies.To create a specific dSTING mutation, we used the method of P element imprecise excision.Homozygous dSTING mutant flies are viable with no obvious observable phenotype.Since the changes in immune response are often accompanied by a dysregulation of metabolic homeostasis and vice versa, we analyzed dSTING mutant flies for the defects in metabolism.Drosophila STING mutants are susceptible to starvation and oxidative stress but have normal life span.Exons are shown as pink colored rectangles.The position of the P element insertion is indicated by the red triangle.Genotypes used were: control flies w, flies with dSTING deletion dSTING, genetic rescue dSTING;GFP dSTING.Percentages of surviving flies at each time point are shown.The percentages of surviving flies were counted every hr.We found that dSTING mutant flies were sensitive to both starvation and oxidative stress as compared to the control flies. To confirm that the observed phenotypes are not due to off target effects, we designed fly strain containing GFP tagged wild type dSTING on the dSTING deletion background.The level of dSTING expression in dSTING;GFP dSTING flies was the same as in control flies. We also looked at the expression pattern of GFP dSTING across adult and larval tissues.The highest level of the expression was observed in the digestive tract in both adults and larvae.Importantly, the expression of GFP dSTING partially or entirely rescued the sensitivity of dSTING deletion flies to both starvation and oxidative stress, suggesting that the observed phenotypes are caused by dSTING deficiency.The larvae carrying dSTING deletion were also more susceptible to both types of stress. The deletion of dSTING had no effect on the total lifespan of fed flies in both males and females.Moreover, the age related mortality was slightly reduced, especially for the females. It is possible that the increased sensitivity to starvation and oxidative stress that we observed in dSTING flies is caused by a lowered defense against commensal or pathogenic bacteria in the absence of dSTING.To test this hypothesis, we generated axenic, or germ free, flies.We found that under axenic condition dSTING mutants exhibited the same response to the starvation and oxidative stress as dSTING non axenic flies. This suggests that diminished immune response against bacteria is not likely to be the cause of the observed phenotypes.Glycogen is another form of a carbohydrate storage that accumulates in the fat body and muscles.We measured storage metabolite levels along with glucose level in fed or hr starved adult males.Under fed conditions, TAG level was decreased twofold in dSTING mutants compared with the control flies.Under starved conditions, TAG level dropped dramatically to about of the level in the control flies.
     
 
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