A Drosophila Model of High Sugar Diet-Induced Cardiomyopathy

Jianbo Na, Laura Palanker Musselman, Jay Pendse, Thomas J. Baranski, Rolf Bodmer, Karen Ocorr, Ross Cagan

Research output: Contribution to journalArticlepeer-review

152 Scopus citations

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.

Original languageEnglish
Article numbere1003175
JournalPLoS genetics
Volume9
Issue number1
DOIs
StatePublished - Jan 2013

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