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: 7.53). 01/2013; 9(1):e1003175. DOI: 10.1371/journal.pgen.1003175
Source: PubMed


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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    • "When flies are fed on high-sugar, they also accumulate lipid droplets, and develop fibrosis-like phenotypes. These phenotypes could be rescued by decreasing the activity of the hexosamine biosynthetic pathway [64]. Additionally, the fly heart has been used as a model system to detail the effects of isocalorically altering nutrient composition on cardiac performance [66]. "
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    • "Several metabolic pathways that process glucose have been shown to be involved in the pathogenesis of diabetes, including the polyol, advanced glycation end products (AGE), PKC, and hexosamine biosynthetic pathways (Brownlee, 2005). Our and others' previous work defined a role for flux through the hexosamine biosynthetic pathway in diet-induced metabolic dysfunction in fly and rat models (Erickson et al., 2013; Na et al., 2013). "
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    Full-text · Article · Jul 2015 · Cell Reports
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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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