Arquier, N. | Search bioRxiv

bioRxiv2024

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. 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 whose cardiac expression is modulated by High Sugar and High Fat regimes. Genes encoding core components of key homeostatic pathways - 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 autonomous and systemic adjustable responses of the heart to nutritional stresses.

physiology↗

bioRxiv2024

Natural variations of aging of cardiac performance in Drosophila identifies a central function for the PAR domain bZIP transcription factor Pdp1/dHLF in cardiac senescence

The identification of genetic factors influencing cardiac senescence in natural populations is central to our understanding of cardiac aging and to identify the etiology of associated cardiac disorders in human populations. However, the genetic underpinning of complex traits in human is almost impossible, due to the infeasibility to control genetic background and gene-environment interactions. Drosophila has striking similarities in cardiac aging with humans, highlighting the conserved nature of cardiac aging for organisms with a heart. Leveraging on a large collection of inbred lines from the Drosophila Genetic Reference Panel (DGRP), we provide an accurate analysis of cardiac senescence in a natural population of flies. This permitted the discovery of an unprecedented number of variants and associated genes significantly associated to the natural variation of cardiac aging. We focused on the function of the PAR-domain bZIP transcription factor Pdp1 for which several variants were found associated with natural variation of the aging of multiple cardiac functional traits. We demonstrated that Pdp1 cell autonomously plays a central role in cardiac senescence and might do so by regulating mitochondria homeostasis. Overall, our work provides a unique resource regarding the genetics of cardiac aging in a natural population.

genetics↗