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Effect of HSD and HFD on cardiac function in Drosophila

ABSTRACT: Type 2 diabetes is a multifactorial disease that has a pandemic development worldwide. Associated cardiac dysfunctions are affecting one-third of the patients. Drosophila has proven to be a valuable model to study cardiac function in physiological and physio-pathological contexts. Indeed, adult flies challenged on rich diets (high sugar or high fat) developed cardiac dysfunctions similar to diabetic cardiomyopathies. In order to better characterize the molecular events leading to these cardiac diseases, we performed an RNA-sequencing on poly(A) extracted from 10 days old female flies reared on ND (Normal Diet), HSD (High Sugar Diet) or HFD (High Fat Diet). The differential expression of genes was evaluated for each rich diet versus normal diet. Genes exhibiting a fold change ≥ 1.5 were considered as good candidates. Gene Ontology analysis for cellular localization showed a significant enrichment in extracellular component. This was supported by the presence of a signal peptide in 27% in HSD and 44% in HFD of the candidate genes. These results suggest that putative new secreted proteins have been identified, putting forward the role of the heart as a secretory organ in hyperglycemia and hyperlipidemia. We functionally validated some interesting candidates by specific cardiac-KO and evaluated the different cardiac phenotypes by high-speed live imaging on undissected flies. We focused on the fit gene, encoding a previously identified satiety hormone and characterized its paracrine as well as its systemic cardiac function in the adult. Our results illustrate a yet unknown cardiac function for the Fit hormone and suggest it as a new fly cardiokine.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE235313 | GEO | 2026/06/03

REPOSITORIES: GEO

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Project description:Obesity has been shown to increase risk for cardiovascular disease and type-2 diabetes. In addition, it has been implicated in aggravation of neurological conditions such as Alzheimer’s. In the model organism Drosophila melanogaster, a physiological state mimicking diet-induced obesity can be induced by subjecting fruit flies to a solid medium disproportionately higher in sugar than protein (HSD) or that has been supplemented with a rich source of saturated fat (HFD). These flies can exhibit increased circulating glucose levels, increased triglyceride content, insulin-like peptide resistance, and behavior indicative of neurological decline, such as decreased climbing ability. We subjected Oregon-R-C flies to variants of the HSD, HFD, or normal (control) diet (ND), followed by a total RNA extraction from fly heads of each diet group for the purpose of Poly-A selected RNA-Sequencing. We targeted at least 50 million paired-end, stranded reads of 75 basepairs in size, and analyzed 4 biological replicates per dietary condition. Our objective was to identify the effects of obesogenic diets on transcriptome patterns, how they differed between obesogenic diets, and identify genes that may relate to pathogenesis accompanying an obesity-like state. Functional annotation and enrichment analysis among genes whose expression was significantly affected by the obesogenic diets indicated an overrepresentation of genes associated with immunity, metabolism, and hemocyanin in the HFD group, and CHK, cell cycle activity, and DNA binding and transcription in the HSD group. Heat map representation of genes affected by both diets illustrated a large fraction of differentially expressed genes between the two diet groups. Diets high in sugar and diets high in fat both have notableeffects on the Drosophila transcriptome in head tissue. The impacted genes, and how they may relate to pathogenesis in the Drosophila obesity-like state, warrant further experimental investigation. Our results also indicate differences in the effects of the HFD and HSD on expression profiles in head tissue of Oregon-R-C flies, despite the reportedly similar phenotypic impacts of the diets.

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Effect of HSD and HFD on cardiac function in Drosophila

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