Qing Zhou, Kai Guo
The present study investigates how perilipin 5 (Plin5), a lipid droplet-associated protein crucial for regulating intracellular lipid metabolism, modulates glycolysis, apoptosis, and mitochondrial function under high glucose conditions, with a focus on its therapeutic potential in diabetic cardiomyopathy (DCM). AC16 human cardiomyocyte cells and human cardiac fibroblasts (HCFs) were transfected with Plin5-overexpressing lentivirus. An in vivo DCM model was established in wild-type and Plin5-knockout mice using a high-fat diet (HFD) combined with streptozotocin injection. Cardiac function was evaluated, and cellular mechanisms were assessed using molecular biology techniques and single-cell RNA sequencing analysis. Plin5 overexpression significantly enhanced glycolysis (e.g. a 2.5-fold increase in extracellular acidification rate, P < 0.001) in both AC16 and HCFs. In AC16 cells, high glucose treatment up-regulated Plin5 expression, whereas in HCFs, it led to down-regulation. Apoptosis-related protein levels, including BCL-2 and cleaved Caspase-3, were modulated by Plin5 overexpression, with a notable impact under high glucose conditions. Cardiac ultrasound revealed significant differences in systolic function (ejection fraction values) across experimental groups. Ki67 staining showed enhanced cardiomyocyte proliferation in Plin5-overexpressing groups under normal glucose conditions, while TUNEL assays indicated reduced apoptosis, though this effect was attenuated under high glucose conditions. Bioinformatics analysis revealed a significant up-regulation of fatty acid metabolism pathways in the diabetic heart, with Plin5 expression specifically increased in cardiomyocytes. In summary, the present study demonstrates that Plin5 plays a critical role in regulating glycolysis, apoptosis, and cardiomyocyte proliferation, particularly under varying glucose conditions, identifying it as a potential therapeutic target for DCM.