Zhu Xiaoqiu, Hua Junyan
Department of Nursing, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China.
The University of Sydney, Camperdown/Darlington Campus, NSW, Australia.
Iran J Public Health. 2025 Jul;54(7):1516-1529. doi: 10.18502/ijph.v54i7.19158.
Extreme obesity pathology is with a risk factor for heart failure (HF), whereas the obesity paradox in HF shows that obese subjects had a good prognosis. The mechanism underlying the obesity paradox in HF prognosis is unclear till now. We aimed to provide evidence for the molecular mechanisms of the obesity paradox in HF.
Differentially expressed genes (DEGs) in ischemic HF samples were identified in the GSE57338 and GSE5406 datasets. Weighted gene co-expression network analysis (WGCNA) modules and a protein-protein interaction network (PPI) were constructed. HF-associated DEGs and pathways were screened in the Comparative Toxicogenomics Database (CTD). The expression of hub genes in adipose tissues from obese patients and LV samples from HF patients were validated in microarray datasets.
Three HF-associated WGCNA modules were identified and DEGs were associated with the 'hsa04115: signaling pathway'. was the only common gene between DEGs and HF-associated genes in the CTD database. The gene was downregulated in the white adipose tissues compared with brown adipose tissues ( = 3.90e-03) and was upregulated in the omental adipose tissues from obese patients compared with lean subjects ( = 3.85e-02).
The downregulation of expression might be responsible for the obesity paradox in HF via interacting with .
极度肥胖病理是心力衰竭（HF）的一个危险因素，而HF中的肥胖悖论表明肥胖受试者预后良好。目前尚不清楚HF预后中肥胖悖论的潜在机制。我们旨在为HF中肥胖悖论的分子机制提供证据。
在GSE57338和GSE5406数据集中鉴定缺血性HF样本中的差异表达基因（DEG）。构建加权基因共表达网络分析（WGCNA）模块和蛋白质-蛋白质相互作用网络（PPI）。在比较毒理基因组学数据库（CTD）中筛选与HF相关的DEG和通路。在微阵列数据集中验证肥胖患者脂肪组织和HF患者左心室样本中枢纽基因的表达。
鉴定出三个与HF相关的WGCNA模块，DEG与“hsa04115：信号通路”相关。是CTD数据库中DEG与HF相关基因之间唯一的共同基因。与棕色脂肪组织相比，该基因在白色脂肪组织中下调（=3.90e-03），与瘦受试者相比，在肥胖患者的网膜脂肪组织中上调（=3.85e-02）。
该基因表达的下调可能通过与相互作用导致HF中的肥胖悖论。
