A040: Exercise Modulates Dilp6 via Foxo to Ameliorate HFD-Induced Lipotoxic Cardiomyopathy in Drosophila

A High-fat diet (HFD) has been shown to cause myocardial lipotoxicity and thus cardiac dysfunction in Drosophila, but the underlying mechanisms and intervention strategies are unclear. Insulin-like growth factor 1 (IGF-1) (Drosophila Dilp6 homologue) plays an important role in adipocyte differentiation, insulin sensitivity. Exercise can improve lipid metabolism disorders, cardiac hypertrophy, and myocardial fibrosis, and effectively prevent lipotoxic cardiomyopathy. Studies have shown that the insulin-regulated transcription factor Foxo positively regulates the expression of Dilp6 in Drosophila adipose bodies. Therefore, the aim of this study was to investigate whether exercise regulates the expression of Dilp6 through the transcription factor Foxo to alleviate HFD-induced lipotoxic cardiomyopathy in Drosophila. Method: W1118 wild-type Drosophila, as well as the UAS-Gal4 system, were used to construct Foxo, Dilp6 knockdown lines of Drosophila. Virgin flies feathered within 12 hours were collected for the following groupings: W1118 high-fat diet and high-fat diet exercise group; Fat-specific Dilp6 knockdown group; fat-specific Foxo knockdown exercise group. RT-qPCR assay, Drosophila cardiac function, and ghost pen cyclic peptide assay were performed. Compared with the normal group, Drosophila cardiac pumping capacity was reduced in the high-fat diet group, and the expression of Foxo and Dilp6 was decreased, and the staining results of ghost pen cyclic peptide showed that the structure of cardiomyocytes was damaged. In contrast, the high-fat exercise group showed significant improvement. 2, the fat-specific Dilp6 knockdown group showed the same phenotype as the high-fat diet group. 3. Compared with the normal exercise group, the expression of Dilp6 in the Foxo knockdown exercise group did not increase significantly. Therefore, the results showed that Foxo regulated the expression of Dilp6, and exercise increased the expression of Dilp6 by upregulating Foxo, thereby improving the cardiomyopathy caused by a high-fat diet and improving the exercise capacity of Drosophila. Exercise ameliorates HFD-induced cardiac dysfunction in Drosophila by upregulating Dilp6 expression through activation of the transcription factor Foxo.