Metabolism fine tuning and cardiokines secretion represent adaptative responses of the heart to High Fat and High Sugar Diets in flies

Cardiopathies are one of the leading causes of death in obese diabetics. Resulting in part from junk food, diabetic cardiomyopathies are notably characterized by contractile dysfunctions. Using the Drosophila model for cardiac function in pathophysiological context, we identified a set of candidate genes, expressed by the heart, whose expression is modulated by acute challenge on High Sugar and High Fat regimes. Genes encoding core components of key homeostatic pathways and proteins such as 1C-metabolism homeostasis, the Galactose metabolism pathway and metabolites transporters, were identified and characterized as adaptative factors of cardiac function under nutritional stresses. In addition, putative secreted proteins were found dysregulated, highlighting the heart as a secretory organ in hyperglycemia and hyperlipidemia. In particular, we characterized the Fit satiety hormone as a new fly cardiokine, which autonomously modulates the cardiac function and remotely affects feeding behavior. Overall, our study uncovered new roles for metabolic pathways and cardiokines, and highlights autonomous and systemic adjustable responses of the heart to nutritional stresses.