Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Institute for Aging and Metabolic Diseases, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Metabolism. 2024 Dec;161:156002. doi: 10.1016/j.metabol.2024.156002. Epub 2024 Aug 22.
Obesity often leads to inadequate angiogenesis in expanding adipose tissue, resulting in inflammation and insulin resistance. We explored the role of placental growth factor (PlGF) in metabolic syndrome (MS) using mice models of type 2 diabetes, high-fat diet, or aging. Reduced serum PlGF levels were associated with decreased insulin sensitivity and development of MS features. PlGF was localized within endothelial cells and pericytes of adipose tissue. In vitro, low PlGF levels in hypoxic conditions worsened oxidative stress, apoptosis, and reduced autophagy. This was associated with a reduction in expression of vascular endothelial growth factor (VEGF)-A/VEGF-R1/-R2, which was influenced by a decrease and increase in PlGF/pAMPK/PI3K-pAkt/PLCγ1-iCa/eNOS and PTEN/GSK3β axes, respectively. PlGF-knockout mice exhibited MS traits through alterations in the same signaling pathways, and these changes were mitigated by recombinant PlGF and metformin. These enhanced angiogenesis and lipid metabolism, underscoring PlGF's role in age-related MS and its potential as a therapeutic target.
肥胖症常导致扩张的脂肪组织中血管生成不足，进而引发炎症和胰岛素抵抗。我们使用 2 型糖尿病、高脂肪饮食或衰老的小鼠模型来探索胎盘生长因子（PlGF）在代谢综合征（MS）中的作用。血清 PlGF 水平降低与胰岛素敏感性降低和 MS 特征的发展有关。PlGF 定位于脂肪组织的内皮细胞和周细胞内。在体外，低氧条件下的低 PlGF 水平会加重氧化应激、细胞凋亡和自噬减少。这与血管内皮生长因子（VEGF）-A/VEGF-R1/-R2 的表达减少有关，这分别受 PlGF/pAMPK/PI3K-pAkt/PLCγ1-iCa/eNOS 和 PTEN/GSK3β 轴的减少和增加的影响。PlGF 敲除小鼠通过相同的信号通路发生 MS 特征改变，而这些变化可通过重组 PlGF 和二甲双胍减轻。这些变化增强了血管生成和脂质代谢，强调了 PlGF 在与年龄相关的 MS 中的作用及其作为治疗靶点的潜力。
