Obesity-Associated Vitamin D Deficiency Correlates with Adipose Tissue DNA Hypomethylation, Inflammation, and Vascular Dysfunction.
Obesity-Associated Vitamin D Deficiency Correlates with Adipose Tissue DNA Hypomethylation, Inflammation, and Vascular Dysfunction.
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DOI：
10.3390/ijms232214377
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发表时间：
2022-11-19
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
维生素D（VD）缺乏是肥胖和血管功能障碍的标志。我们试图验证这一假设，即VD缺乏可能通过诱导脂肪因子低甲基化和表达增强而导致肥胖相关的血管功能障碍。为此，我们收集了血液和脂肪组织（AT）从一个队列的77名肥胖参与者谁被归类为有轻度，中度或重度VD缺乏。测量了身体组成、血管反应性、心脏代谢谱和94种炎症相关脂肪因子的DNA甲基化。我们的研究结果表明，较高程度的VD缺陷与较低的DNA甲基化相关，并诱导AT中炎性脂肪因子如B细胞淋巴瘤6（BCL 6）、C-X-C基序趋化因子配体8（CXCL 8）、组蛋白脱乙酰酶5（HDAC 5）、白细胞介素12 A（IL 12 A）和核因子κB（NFκB）的表达。他们还与较高的BMI和总脂肪量和内脏脂肪量，受损的胰岛素敏感性和血脂谱，AT缺氧，和较高浓度的循环炎症标志物。中度和重度VD缺乏与肱动脉和AT孤立性小动脉的血管反应性受损、一氧化氮生成减少和动脉僵硬度增加相关。在多变量回归分析中，VD缺乏水平强烈预测脂肪因子甲基化评分、全身炎症和微血管功能障碍。总之，我们的研究结果表明，VD缺乏是一个可能的贡献者肥胖相关的脂肪因子低甲基化，炎症和血管功能障碍。
Vitamin D (VD) deficiency is a hallmark of obesity and vascular dysfunction. We sought to test the hypothesis that VD deficiency may contribute to obesity-related vascular dysfunction by inducing adipokine hypomethylation and augmented expression. To this end, we collected blood and adipose tissues (ATs) from a cohort of 77 obese participants who were classified as having mild, moderate, or severe VD deficiency. The body composition, vascular reactivity, cardiometabolic profiles, and DNA methylation of 94 inflammation-related adipokines were measured. Our results show that higher degrees of VD deficiency were associated with lower DNA methylation and induced the expression of inflammatory adipokines such as B-cell lymphoma 6 (BCL6), C-X-C Motif Chemokine Ligand 8 (CXCL8), histone deacetylase 5 (HDAC5), interleukin 12A (IL12A), and nuclear factor κB (NFκB) in the ATs. They were also associated with higher BMI and total and visceral fat mass, impaired insulin sensitivity and lipid profiles, AT hypoxia, and higher concentrations of circulating inflammatory markers. Moderate and severe VD deficiency correlated with impaired vasoreactivity of the brachial artery and AT-isolated arterioles, reduced nitric oxide generation, and increased arterial stiffness. In a multivariate regression analysis, the VD deficiency level strongly predicted the adipokine methylation score, systemic inflammation, and microvascular dysfunction. In conclusion, our findings suggest that VD deficiency is a possible contributor to obesity-related adipokine hypomethylation, inflammation, and vascular dysfunction.
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