Work

Downregulated DKK2 may serve as a molecular mechanism of high-fat diet-induced myocardial injury via Wnt/β-catenin pathway

Year: 2024

Type: article

Abstract: OBJECTIVE: High-fat diet could induce structural and functional disorders of the heart, but the underlying mechanism remains elusive. This study aimed to explore related mechanism of obesity cardiomyopathy. METHODS: Obesity model was established by feeding rats with a high-fat diet, and H9c2 cells were stimulated with palmitic acid to mimic high-fat stimulation. Whole transcriptome analysis results showed that the expression of Dickkopf-2 (DKK2) in obesity cardiomyopathy group was significantly lower than that in control group and simple obesity group. Overexpression and knockdown of DKK2 was achieved by infection with lentivirus. Weight, blood glucose, lipids, blood pressure, and insulin, HE staining, Sirius red staining and echocardiography results were analyzed in rats at 8 and 16 weeks after various interventions. qRT-PCR and western blots were used to detect the expression of RNAs and proteins. RESULTS: High-fat diet-induced obese rats presented with changes in serum lipid, insulin, and increases in myocardial inflammation and fibrosis. Protein and mRNA expression levels of DKK2 were significantly decreased in the obesity cardiomyopathy group compared with the obesity and control group. In vitro, knockdown of DKK2 activated β-catenin/Wnt3a pathway, while overexpress of DKK2 inhibited β-catenin/Wnt3a expression. CONCLUSION: Activating DKK2 may serve as a novel therapeutic intervention option for obesity cardiomyopathy and obesity-related metabolic disorders, and future studies are needed to validate this hypothesis.

Source: Life Sciences

DOI: 10.1016/j.lfs.2024.123306