Yixuan Wang, Di Chen, Ye Pu, Jiahao Shi, Congxiang Yi, Jie Chen, Guangxiang Yang, Yang Cui, Yu Nie, Liyuan Zhang, Xiaowei Wei, Qin Yu
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引用次数: 0
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.
期刊介绍：
Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed.
The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.
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