Identification of lipid metabolism-related genes in dapagliflozin treated rats with diabetic cardiomyopathy by bioinformatics.

IF 3.9 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Frontiers in Endocrinology Pub Date : 2025-03-20 eCollection Date: 2025-01-01 DOI:10.3389/fendo.2025.1525831
Xun Huang, Yunhong Wang, Rong Wan, Zhigang You, Lin Huang
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引用次数: 0

Abstract

Background: Diabetic cardiomyopathy (DCM) is a heart disease caused by the metabolic disorders of glucose and lipids associated with diabetes, leading to heart failure and death in diabetic patients. Dapagliflozin (DAPA) serves as a treatment for managing blood glucose levels in individuals with type 2 diabetes mellitus (DM). However, the specific mechanisms by which DAPA treats DCM are not yet fully understood.

Methods: Sprague-Dawley (SD) rats (n = 5/group) were randomly divided into control, model, and intervention groups. Lipid metabolism-related genes (LMRGs) were gotten from publicly available database. Differential expression analysis of model vs. control and intervention vs. model samples was performed to obtain differentially expressed genes (DEGs), and the result was recorded as DEGs-Model and DEGs-Intervention. The intersection of genes with opposing expression trends between DEGs-Model and DEGs-Intervention were considered as candidate genes. Subsequently, candidate genes and LMRGs were intersected to acquire hub genes, and the expression of hub genes was analyzed in each group of samples. Then, the mechanism of action of these hub genes were investigated through functional enrichment analysis, gene set enrichment analysis (GSEA), and predictive of m6A binding sites.

Results: Ultimately, 68 candidate genes and 590 LMRGs were intersected to derive 2 hub genes (Acsbg1 and Etnppl). Acsbg1 was significantly increase in model group compared with control group. RT-qPCR results confirmed Acsbg1 was obviously higher expression in model group, while Etnppl was significantly lower expression in model group compare to control groups and intervention group. While the expression of Etnppl was significantly increase in intervention group compared with model group. Functional enrichment analyses indicated that Acsbg1 and Etnppl were associated with fatty acid metabolism. The findings of GSEA indicated that Acsbg1 and Etnppl might affect the occurrence and progression of DCM through lysosome. And the Acsbg1 and Etnppl were located at UCAGG in the RNA secondary structure.

Conclusion: This study identified 2 hub genes (Acsbg1 and Etnppl) as potential new focal points for diagnosing and treating DCM.

应用生物信息学方法鉴定达格列净治疗的糖尿病性心肌病大鼠脂质代谢相关基因。
背景:糖尿病性心肌病(Diabetic cardiomyopathy, DCM)是一种与糖尿病相关的葡萄糖和脂质代谢紊乱引起的心脏病,可导致糖尿病患者心力衰竭和死亡。达格列净(DAPA)用于控制2型糖尿病(DM)患者的血糖水平。然而,DAPA治疗DCM的具体机制尚不完全清楚。方法:SD大鼠(n = 5/组)随机分为对照组、模型组和干预组。脂质代谢相关基因(LMRGs)从公开数据库中获取。对模型与对照组、干预与模型样本进行差异表达分析,获得差异表达基因(DEGs),记录为DEGs- model和DEGs- intervention。将DEGs-Model和DEGs-Intervention表达趋势相反的基因交集作为候选基因。随后,将候选基因与LMRGs相交获得枢纽基因,并分析各组样品中枢纽基因的表达情况。然后,通过功能富集分析、基因集富集分析(GSEA)和预测m6A结合位点来研究这些枢纽基因的作用机制。结果:最终,68个候选基因和590个LMRGs相交,得到2个枢纽基因(Acsbg1和Etnppl)。与对照组相比,模型组Acsbg1显著升高。RT-qPCR结果证实Acsbg1在模型组的表达明显高于对照组和干预组,Etnppl在模型组的表达明显低于对照组和干预组。干预组与模型组比较,Etnppl的表达明显升高。功能富集分析表明Acsbg1和Etnppl与脂肪酸代谢有关。GSEA结果提示Acsbg1和Etnppl可能通过溶酶体影响DCM的发生和发展。Acsbg1和Etnppl位于RNA二级结构的UCAGG上。结论:本研究发现Acsbg1和Etnppl两个中心基因可能是诊断和治疗DCM的新焦点。
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来源期刊
Frontiers in Endocrinology
Frontiers in Endocrinology Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
5.70
自引率
9.60%
发文量
3023
审稿时长
14 weeks
期刊介绍: Frontiers in Endocrinology is a field journal of the "Frontiers in" journal series. In today’s world, endocrinology is becoming increasingly important as it underlies many of the challenges societies face - from obesity and diabetes to reproduction, population control and aging. Endocrinology covers a broad field from basic molecular and cellular communication through to clinical care and some of the most crucial public health issues. The journal, thus, welcomes outstanding contributions in any domain of endocrinology. Frontiers in Endocrinology publishes articles on the most outstanding discoveries across a wide research spectrum of Endocrinology. The mission of Frontiers in Endocrinology is to bring all relevant Endocrinology areas together on a single platform.
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