A Drosophila model of high sugar diet-induced cardiomyopathy.
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...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1003175&type=printable |
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| author | Jianbo Na Laura Palanker Musselman Jay Pendse Thomas J Baranski Rolf Bodmer Karen Ocorr Ross Cagan |
| author_facet | Jianbo Na Laura Palanker Musselman Jay Pendse Thomas J Baranski Rolf Bodmer Karen Ocorr Ross Cagan |
| author_sort | Jianbo Na |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-aa585e4dd82c4bcda7449113b0f59fe9 |
| institution | DOAJ |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-aa585e4dd82c4bcda7449113b0f59fe92025-08-20T03:01:15ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042013-01-0191e100317510.1371/journal.pgen.1003175A Drosophila model of high sugar diet-induced cardiomyopathy.Jianbo NaLaura Palanker MusselmanJay PendseThomas J BaranskiRolf BodmerKaren OcorrRoss CaganDiets 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.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1003175&type=printable |
| spellingShingle | Jianbo Na Laura Palanker Musselman Jay Pendse Thomas J Baranski Rolf Bodmer Karen Ocorr Ross Cagan A Drosophila model of high sugar diet-induced cardiomyopathy. PLoS Genetics |
| title | A Drosophila model of high sugar diet-induced cardiomyopathy. |
| title_full | A Drosophila model of high sugar diet-induced cardiomyopathy. |
| title_fullStr | A Drosophila model of high sugar diet-induced cardiomyopathy. |
| title_full_unstemmed | A Drosophila model of high sugar diet-induced cardiomyopathy. |
| title_short | A Drosophila model of high sugar diet-induced cardiomyopathy. |
| title_sort | drosophila model of high sugar diet induced cardiomyopathy |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1003175&type=printable |
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