title: A Drosophila model of high sugar diet-induced cardiomyopathy.
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.
authors: Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, New York, United States of America.
authors: Jianbo
authors: J
authors: Na
authors: Laura Palanker
authors: LP
authors: Musselman
authors: Jay
authors: J
authors: Pendse
authors: Thomas J
authors: TJ
authors: Baranski
authors: Rolf
authors: R
authors: Bodmer
authors: Karen
authors: K
authors: Ocorr
authors: Ross
authors: R
authors: Cagan
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000235:genetics / Q000503:physiopathology; D004032:Diet; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology; D005947:Glucose / Q000737:chemistry / Q000378:metabolism; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology; D006595:Hexosamines / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D015398:Signal Transduction
chemical_list: D006595:Hexosamines; D007328:Insulin; D005947:Glucose