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西方饮食模式和阿托伐他汀诱导奥萨巴野猪心外膜脂肪组织干扰素信号。

A Western-type dietary pattern and atorvastatin induce epicardial adipose tissue interferon signaling in the Ossabaw pig.

机构信息

Cardiovascular Nutrition Laboratory, JM USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA.

USDA, ARS, Beltsville Human Nutrition Research Center, Diet Genomics and Immunology Laboratory, Beltsville, MD.

出版信息

J Nutr Biochem. 2019 May;67:212-218. doi: 10.1016/j.jnutbio.2019.02.003. Epub 2019 Feb 20.

Abstract

Epicardial adipose tissue (EAT) inflammation is thought to potentiate the development of coronary artery disease (CAD). Overall diet quality and statin therapy are important modulators of inflammation and CAD progression. Our objective was to examine the effects and interaction of dietary patterns and statin therapy on EAT gene expression in the Ossabaw pig. Pigs were randomized to 1 of 4 groups; Heart Healthy diet (high in unsaturated fat, unrefined grain, fruits/vegetables [HHD]) or Western diet (high in saturated fat, cholesterol, refined grain [WD]), with or without atorvastatin. Diets were fed in isocaloric amounts for 6 months. A two-factor edge R analysis identified the differential expression of 21 genes. Relative to the HHD, the WD resulted in a significant 12-fold increase of radical s-adenosyl methionine domain containing 2 (RSAD2), a gene induced by interferon signaling. Atorvastatin led to the significant differential expression of 17 genes predominately involved in interferon signaling. Results were similar using the Porcine Translational Research Database. Pathway analysis confirmed the up-regulation of interferon signaling in response to the WD and atorvastatin independently. An expression signature of the largely interferon related differentially expressed genes had no predictive capability on a histological assessment of atherosclerosis in the underlying coronary artery. These results suggest that a WD and atorvastatin evoke an interferon mediated immune response in EAT of the Ossabaw pig, which is not associated with the presence of atherosclerosis.

摘要

心外膜脂肪组织(EAT)炎症被认为是促进冠状动脉疾病(CAD)发展的因素。整体饮食质量和他汀类药物治疗是炎症和 CAD 进展的重要调节剂。我们的目的是研究饮食模式和他汀类药物治疗对 Ossabaw 猪心外膜脂肪组织基因表达的影响及其相互作用。猪被随机分为 4 组中的 1 组;富含不饱和脂肪、未精制谷物、水果/蔬菜的健康心脏饮食(HHD)或富含饱和脂肪、胆固醇、精制谷物的西方饮食(WD),并接受阿托伐他汀治疗或不接受治疗。6 个月内以等热量的方式喂养这些饮食。双因素边缘 R 分析确定了 21 个基因的差异表达。与 HHD 相比,WD 导致自由基 s-腺苷甲硫氨酸结构域包含 2(RSAD2)的基因表达显著增加了 12 倍,该基因是由干扰素信号诱导的。阿托伐他汀导致 17 个主要涉及干扰素信号的基因的差异表达。使用猪转化研究数据库得到了类似的结果。途径分析证实,WD 和阿托伐他汀均可独立上调干扰素信号。干扰素相关差异表达基因的表达谱对基础冠状动脉粥样硬化的组织学评估没有预测能力。这些结果表明,WD 和阿托伐他汀在 Ossabaw 猪的心外膜脂肪组织中引起干扰素介导的免疫反应,而这种反应与动脉粥样硬化的存在无关。

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