Study of the endocrine function of the heart in diabetic cardiomyopathies in Drosophila melanogaster

Abstract

Cardiopathies are increased by 35% in patients with diabetes. The development of metabolic cardiomyopathies is due to imbalanced eating behavior, lack of exercise but also favored by genetic context. However, the genetic causes of obesity-related cardiomyopathies are still poorly identified. Our group is interested in identifying the genetic factors involved in the cardiac response to metabolic disorders using Drosophila as a model system. Indeed, most of the physiological regulatory mechanisms are highly conserved in Drosophila and it is therefore a proven model system to in vivo analyze physiological mechanisms which are much more complex to study in mammals. In particular, fruit flies fed a high-fat or a high-sugar diet develop signs of obesity that are also associated with cardiomyopathies very similar to the mammalian ones. The heart is now considered as an endocrine organ, secreting molecules in the bloodstream in healthy or stress contexts. Our project notably aims at identifying new molecules secreted by the heart in nutritional stress conditions in order to better understand the context of the diabetic cardiomyopathies development. Using our model system, we performed a transcriptomic analysis on isolated Drosophila adult hearts that have been challenged in three nutritional conditions (high-sugar, high-fat and normal diet). Among the candidate genes, several encode known or putative secreted proteins, strongly suggesting that we potentially identified cardiokines molecules (cytokines secreted by the heart). We are characterizing the role of these genes in the development of diabetic cardiomyopathies and in the regulation of organismal homeostasis. Some cardiac genes are modulated by nutritional stress. Among the identified candidates, known or putative secreted proteins strongly suggest that the heart is involved as an endocrine organ in the metabolic disorders and the cardiomyopathies associated.