A Drosophila Model of High Sugar Diet-Induced Cardiomyopathy

Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, New York, United States of America.
PLoS Genetics (Impact Factor: 8.17). 01/2013; 9(1):e1003175. DOI: 10.1371/journal.pgen.1003175
Source: PubMed

ABSTRACT Diets high in carbohydrates have long been linked to progressive heart dysfunction, yet the mechanisms by which chronic high sugar leads to heart failure remain poorly understood. Here we combine diet, genetics, and physiology to establish an adult Drosophila melanogaster model of chronic high sugar-induced heart disease. We demonstrate deterioration of heart function accompanied by fibrosis-like collagen accumulation, insulin signaling defects, and fat accumulation. The result was a shorter life span that was more severe in the presence of reduced insulin and P38 signaling. We provide evidence of a role for hexosamine flux, a metabolic pathway accessed by glucose. Increased hexosamine flux led to heart function defects and structural damage; conversely, cardiac-specific reduction of pathway activity prevented sugar-induced heart dysfunction. Our data establish Drosophila as a useful system for exploring specific aspects of diet-induced heart dysfunction and emphasize enzymes within the hexosamine biosynthetic pathway as candidate therapeutic targets.

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    • "Although the correlation between temperature and heart rate has been demonstrated in several insect orders, most of what we know about the effect of diet on heart physiology comes from studies done on the fruit fly, Drosophila melanogaster. In this fly species, balanced low calorie diets result in lower myocardial lipid levels and increased cardiac performance (Bazzell et al., 2013; Birse et al., 2010; Lim et al., 2011), whereas diets that are high in sugar induce cardiomyopathy (Na et al., 2013). In Periplaneta americana nymphs, food deprivation does not induce noticeable changes in heart physiology, but food deprivation in aquatic Anopheles quadrimaculatus larvae results in a decrease in the heart rate (Jones, 1956, 1977). "
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    Journal of Insect Physiology 01/2015; 74. DOI:10.1016/j.jinsphys.2015.01.011 · 2.50 Impact Factor
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    • "À/À or D-p38b À/À hearts exhibited no defects under baseline conditions (Na et al., 2013). These heart abnormalities in the double mutant were reminiscent of the cardiac effects of flies with reduced pericardial ROS levels, suggesting that D-p38a/D-p38b might be involved in ROS signaling in PCs. "
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    ABSTRACT: Comparative structural analyses of the heart and associated tissues in 4th instar larvae (L4), pupae and adults of Aedes aegypti were undertaken using a combination of microscopy techniques. The Ae. aegypti heart consists of cardiomyocytes arranged in a helical fashion, and it is physically associated with intersegmental groups of pericardial cells (PCs) and the alary muscles (AMs). Ramifications commonly present in AMs are more developed in adults than in the immature stages. Pericardial cells absorb and store extracellular components as shown by the uptake of carmine dye fed in larval diet. We also observed that carmine stained inclusions corresponded to electron-dense structures resembling lysosomes that were more abundant and prominent in pupae, suggestive of increase of waste accumulation during pupation. The results presented here expand on previously known aspects of the mosquito heart and describe for the first time comparative aspects of the morphology of the heart in different developmental stages.
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