Diosgenin regulates adipokine expression in perivascular adipose tissue and ameliorates endothelial dysfunction via regulation of AMPK
Diosgenin regulates adipokine expression in perivascular adipose tissue and ameliorates endothelial dysfunction via regulation of AMPK
复制标题
薯蓣皂苷元通过调节 AMPK 调节血管周围脂肪组织中的脂肪因子表达并改善内皮功能障碍
DOI：
10.1016/j.jsbmb.2015.07.005
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发表时间：
2016-01-01
影响因子：
4.1
通讯作者：
Kou, Junping
中科院分区：
文献类型：
--
作者：
Chen, Yan;Xu, Xiaoshan;Kou, Junping
血管周围脂肪组织（PVAT）由于其对血管壁内细胞的旁分泌作用而被认为是血管功能的积极贡献者。本研究旨在探讨薯蓣皂苷元对PVAT中脂肪因子表达的影响，重点是对内皮功能的调节。棕榈酸（PA）刺激诱导炎症和脂肪因子表达失调的PVAT。薯蓣皂苷元治疗抑制IKK β磷酸化，下调促炎细胞因子/蛋白质的mRNA表达，包括肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、单核细胞趋化蛋白（MCP-1）和诱导型一氧化氮合酶（iNOS），而脂联素、过氧化物酶体增殖物激活受体γ（PPAR γ）和腺苷酸酶1（Arg-1）的基因表达降低被薯蓣皂苷元治疗逆转。薯蓣皂苷元在PVAT的基础和炎症条件下增强AMPK磷酸化，而通过siRNA敲低AMPK减弱其调节作用，表明薯蓣皂苷元以AMPK依赖性方式抑制炎症。我们从PA刺激的PVAT制备条件培养基诱导内皮功能障碍，发现用薯蓣皂苷元预处理PVAT有效地恢复了大鼠主动脉ACh诱导的血管舒张功能的丧失，并增加了eNOS磷酸化。高脂饮食喂养大鼠诱导炎症PVAT和内皮依赖性血管舒张功能的损害，而这些改变被预防口服剂量为20和40毫克/公斤的薯蓣皂苷元。总之，所获得的数据表明，薯蓣皂苷元改善炎症相关的脂肪因子失调，从而防止内皮功能障碍。我们的研究结果将为薯蓣皂苷元保护内皮功能免受炎症损伤的潜在机制提供新的见解。(C)2015爱思唯尔有限公司版权所有。
Perivascular adipose tissue (PVAT) has been recognized as an active contributor to vascular function due to its paracrine effects on cells contained within vascular wall. The present study was designed to investigate the effect of diosgenin on adipokine expression in PVAT with emphasis on the regulation of endothelial function. Palmitic acid (PA) stimulation induced inflammation and dysregulation of adipokine expression in PVAT. Diosgenin treatment inhibited IKK beta phosphoiylation and downregulated mRNA expressions of proinflammatory cytokines/proteins including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), monocyte chemoattractant protein (MCP-1), and inducible nitric oxide synthase (iNOS), while reduced gene expressions for adiponectin, PPAR gamma, and arginase 1 (Arg-1) were reversed by diosgenin treatment. Diosgenin enhanced AMPK phosphorylation under basal and inflammatory conditions in PVAT, whereas knockdown of AMPK by SiRNA diminished its modulatory effect, indicating that diosgenin inhibited inflammation in an AMPK-dependent manner. We prepared conditioned medium from PA-stimulated PVAT to induce endothelial dysfunction and found that pre-treatment of PVAT with diosgenin effectively restored the loss of ACh-induced vasodilation and increased eNOS phosphorylation in rat aorta. High-fat diet feeding in rats induced inflammation in PVAT and the impairment of endothelium-dependent vasodilation, whereas these alterations were prevented by oral administration of diosgenin at doses of 20 and 40 mg/kg. In conclusion, the obtained data showed that diosgenin ameliorated inflammation-associated adipokine dysregulation, and thereby prevented endothelial dysfunction. Our findings would shed a novel insight into the potential mechanism by which diosgenin protected endothelial function against inflammatory insult. (C) 2015 Elsevier Ltd. All rights reserved.