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High sugar diets exacerbate type two diabetes and cardiovascular disease in humans and model organisms, including Drosophila melanogaster. High sugar diets are linked to cardiovascular disease through lipotoxicity, which causes lipid accumulation in the blood and organs. While the lipids and mechanisms underlying lipotoxicity are not well understood, increased abundance of cardiac diacylglycerides, triacylglycerides, and other lipids is strongly associated with impaired cardiovascular function. We used tissue-specific loss-of-function genetics to target genes that we hypothesized might contribute to the accumulation of toxic lipid species in Drosophila. Genes encoding enzymes in several metabolic pathways were knocked down in a screen in the fat body, an adipose-like organ that exhibits endocrine control of systemic metabolism. We measured the impact of chronic high sugar feeding on heart function by testing each genotype's ability to tolerate cardiac stress. A number of proteins were found that were able to ameliorate or exacerbate cardiac stress-induced heart failures. Elucidating lipotoxicity pathways may lead to the discovery of targets for treating cardiovascular disease.



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Identification of genes that affect cardiac failure in diabetic Drosophila melanogaster