Diet-mediated diseases represent an increasing challenge in Western society. Particular attention has focused recently on carbohydrate consumption, which has increased as much as 41% in the past three decades 
. Dietary sugars have in turn been linked a variety of metabolism-related problems including obesity, insulin resistance, metabolic syndrome, and type 2 diabetes mellitus (T2DM). Heart tissue is thought to be especially sensitive to changes in sugar and insulin flux 
. Elevated levels of hemoglobin A1c—a measure of long-term blood glucose levels—is an independent risk factor for heart disease in both diabetics and non-diabetics 
. Regular consumption of sugar-sweetened beverages is associated with a higher risk of coronary heart disease 
. In addition to coronary heart disease progression of T2DM can lead to diabetic cardiomyopathy, defined as functional or structural defects of myocardial structures in the absence of coronary artery disease or hypertension 
. As a result, the American Heart Association has recently recommended limiting sources of sugar in the diet 
. Despite important advances in our understanding of the effects of dietary sugars, our knowledge of the mechanisms that direct sugar-induced heart disease remains incomplete.
provides a useful complement to mammalian models. Their short life span and powerful genetic tools permit detailed in situ
organ analysis. While flies show important differences from their mammalian counterparts, they also show marked similarities. For example, the fly genome encodes seven insulin-like peptide genes (Dilp 1–7) that activate classical insulin pathway signaling 
. Ablation of insulin producing cells phenocopied several aspects of type 1 diabetes 
. Further, recent data have indicated that Drosophila
is susceptible to diet-mediated metabolic and cardiac organ dysfunctions that are reminiscent of those reported in mammals 
heart shows both similarities and differences to the mammalian heart. It is a linear heart tube that is divided into four chambers by rudimentary valve-like structures. Drosophila
have an open circulatory system with a separate tracheal system used for oxygen transport and their hearts are devoid of coronary arteries 
. This separation of oxygen delivery from cardiac pumping function has the advantage that alterations in heart function do not immediately affect viability. demonstrates the ventral view of the heart, showing the longitudinal and alary muscles that cover and stabilize the heart tube, respectively 
. provides a dorsal view of the heart, showing the myocardial cells that form the heart tube and ostia that provide an entry point for hemolymph. Conserved mechanisms of heart development and function are shared between flies and vertebrates 
. Recently, increasingly robust tools have been developed to image the fly heart and to characterize its physiological function 
. A Drosophila
age-related heart disease model has been established and several genes that regulate age-mediated damage have been identified 
. Recently, a high fat diet-induced obesity model has been developed in Drosophila
that leads to severe cardiac malfunction, demonstrating the utility of this genetic system for studying fundamental aspects of organismal metabolic disorders 
is limited as a model for particular aspects of diabetes and diabetic cardiomyopathy including hypertension and vascular defects. Nevertheless, it provides an opportunity to explore specific aspects of metabolic dysfunction and heart function.
Drosophila model of diabetic cardiomyopathy.
Here we develop the Drosophila heart as a new model for the study of diet-induced heart dysfunction. Flies were raised on a high-sucrose diet (HSD) to provoke specific aspects of diet-induced metabolic dysfunction including aspects of T2DM. We demonstrate progressive and specific dysfunctions emerging in the hearts of adult flies fed an HSD. We further validate our model by demonstrating that two pathways previously shown to mediate heart dysfunction in mammals— the insulin and P38 MAPK pathways— modulate HSD-induced heart defects in Drosophila as well. Finally, we present evidence that dietary sucrose directs heart damage in part by its flux through the hexosamine biosynthetic pathway. Increasing hexosamine flux phenocopied sugar-mediated heart dysfunction and also led to structural damage. Importantly, decreasing pathway activity led to a significant reduction in sucrose-mediated heart damage, suggesting specific enzyme targets that may prove useful for reducing the effects of high dietary sugars on heart function.