Adipose Tissue Hypoxia Correlates with Adipokine Hypomethylation and Vascular Dysfunction.
Adipose Tissue Hypoxia Correlates with Adipokine Hypomethylation and Vascular Dysfunction.
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DOI：
10.3390/biomedicines9081034
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发表时间：
2021-08-18
期刊：
影响因子：
4.7
通讯作者：
Mahmoud AM
中科院分区：
文献类型：
--
作者：
Ali MM;Hassan C;Masrur M;Bianco FM;Naquiallah D;Mirza I;Frederick P;Fernandes ET;Giulianotti CP;Gangemi A;Phillips SA;Mahmoud AM
肥胖的特征是功能失调的脂肪组织堆积，这容易导致心脏代谢性疾病。我们先前的体外研究表明，低氧在诱导脂肪细胞脂肪因子低甲基化中起作用。我们试图在肥胖者的内脏脂肪组织(VAT)中检查这种机制及其与心脏代谢危险因素的相关性。我们提出了低氧诱导因子HIF1TET1DNA羟甲基酶α的参与。血液样本和增值税活检分别来自肥胖者和非肥胖者(n=60)，分别接受减肥手术和择期手术。VAT分析显示肥胖组较对照组血管密度降低，HIF1α和TET1蛋白水平升高。在肥胖者的VAT中观察到整体低甲基化和羟甲基化，以及几种促炎性脂肪因子的启动子低甲基化。在低甲基化脂肪因子启动子附近富含Tet1蛋白。脂肪因子甲基化的平均水平与血管和小动脉血管反应性呈正相关，与相应增值税样本中HIF1、α和TET1的蛋白水平、血清和组织炎症标志物以及其他心脏代谢危险因素呈负相关。这些发现表明，脂肪组织缺氧在导致表观遗传学改变中发挥了作用，这可以解释肥胖患者脂肪细胞因子产生增加，最终导致血管功能障碍。
Obesity is characterized by the accumulation of dysfunctional adipose tissues, which predisposes to cardiometabolic diseases. Our previous in vitro studies demonstrated a role of hypoxia in inducing adipokine hypomethylation in adipocytes. We sought to examine this mechanism in visceral adipose tissues (VATs) from obese individuals and its correlation with cardiometabolic risk factors. We propose an involvement of the hypoxia-inducible factor, HIF1α, and the DNA hydroxymethylase, TET1. Blood samples and VAT biopsies were obtained from obese and non-obese subjects (n = 60 each) having bariatric and elective surgeries, respectively. The analyses of VAT showed lower vascularity, and higher levels of HIF1α and TET1 proteins in the obese subjects than controls. Global hypomethylation and hydroxymethylation were observed in VAT from obese subjects along with promoter hypomethylation of several pro-inflammatory adipokines. TET1 protein was enriched near the promotor of the hypomethylated adipokines. The average levels of adipokine methylation correlated positively with vascularity and arteriolar vasoreactivity and negatively with protein levels of HIF1α and TET1 in corresponding VAT samples, serum and tissue inflammatory markers, and other cardiometabolic risk factors. These findings suggest a role for adipose tissue hypoxia in causing epigenetic alterations, which could explain the increased production of adipocytokines and ultimately, vascular dysfunction in obesity.
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影响因子：
3.5
作者：
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通讯作者：
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