title: Obesity-associated cardiac dysfunction in starvation-selected Drosophila melanogaster.
abstract: There is a clear link between obesity and cardiovascular disease, but the complexity of this interaction in mammals makes it difficult to study. Among the animal models used to investigate obesity-associated diseases, Drosophila melanogaster has emerged as an important platform of discovery. In the laboratory, Drosophila can be made obese through lipogenic diets, genetic manipulations, and adaptation to evolutionary stress. While dietary and genetic changes that cause obesity in flies have been demonstrated to induce heart dysfunction, there have been no reports investigating how obesity affects the heart in laboratory-evolved populations. Here, we studied replicated populations of Drosophila that had been selected for starvation resistance for over 65 generations. These populations evolved characteristics that closely resemble hallmarks of metabolic syndrome in mammals. We demonstrate that starvation-selected Drosophila have dilated hearts with impaired contractility. This phenotype appears to be correlated with large fat deposits along the dorsal cuticle, which alter the anatomical position of the heart. We demonstrate a strong relationship between fat storage and heart dysfunction, as dilation and reduced contractility can be rescued through prolonged fasting. Unlike other Drosophila obesity models, the starvation-selected lines do not exhibit excessive intracellular lipid deposition within the myocardium and rather store excess triglycerides in large lipid droplets within the fat body. Our findings provide a new model to investigate obesity-associated heart dysfunction.
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada; christopher.hardy@unlv.edu.
authors.forename: Christopher M
authors.identifier: http://orcid.org/0000-0003-0364-9756
authors.initials: CM
authors.lastname: Hardy
authors.affiliation: Development, Aging and Regeneration Program, Sanford Burnham Medical Research Institute, La Jolla, California;
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Birse
authors.affiliation: Department of Medicine, Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia; and.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Wolf
authors.affiliation: School of Medicine-Cardiology, Duke University, Durham, North Carolina.
authors.forename: Lin
authors.initials: L
authors.lastname: Yu
authors.affiliation: Development, Aging and Regeneration Program, Sanford Burnham Medical Research Institute, La Jolla, California;
authors.forename: Rolf
authors.initials: R
authors.lastname: Bodmer
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, Nevada;
authors.forename: Allen G
authors.initials: AG
authors.lastname: Gibbs
mesh_terms: D000818:Animals; D004331:Drosophila melanogaster; D005216:Fat Body / Q000378:metabolism; D006331:Heart Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D007814:Larva; D050356:Lipid Metabolism / Q000502:physiology; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000150:complications* / Q000503:physiopathology; D013217:Starvation / Q000503:physiopathology*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D014280:Triglycerides
keywords: Drosophila melanogaster; heart disease; laboratory natural selection; obesity; starvation selection