Hou Ningning, Du Gang, Han Fang, Zhang Jin, Jiao Xiaotong, Sun Xiaodong
Department of Endocrinology, Weifang, China.
Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, China.
Cell Physiol Biochem. 2017;42(2):603-614. doi: 10.1159/000477864. Epub 2017 Jun 9.
To determine whether irisin could improve endothelial dysfunction by regulating heme oxygenase-1(HO-1)/adiponectin axis in perivascular adipose tissue (PVAT) in obesity.
Male C57BL/6 mice were fed with a high-fat diet (HFD) with or without irisin treatment. Endothelium-dependent vasorelaxation of the thoracic aorta with or without PVAT (PVAT+ or PVAT-) was determined. Western blot was employed to determine the levels of HO-1 and adiponectin in PVAT. UCP-1, Cidea, and TNF-α gene expression in PVAT were tested by real-time PCR.
The presence of PVAT significantly impaired endothelial function in the HFD mice. Treatment of HFD mice with irisin significantly restored this impairment and improved endothelial function in vivo or ex vivo. Incubated aortic rings (PVAT-) with PVAT-derived conditioned medium (CM) from HFD mice impaired endothelial function in control mice. This impairment was prevented by incubating the aortic rings (PVAT-) from HFD mice with PVAT-derived CM from irisin. However, the beneficial effects were partly attenuated in the presence of HO-1 inhibitor and adiponectin receptor blocking peptide. Treatment of HFD mice with irisin significantly increased NO production, protein levels of HO-1 and adiponectin, mRNA expressions of UCP-1 and Cidea, and decreased superoxide production and TNF-α expression in PVAT.
Irisin improved endothelial function by modulating HO-1/ adiponectin axis in PVAT in HFD-induced obese mice. These findings suggest that regulating PVAT function may be a potential mechanism by which irisin improves endothelial function in obesity.
确定鸢尾素是否可通过调节肥胖小鼠血管周围脂肪组织（PVAT）中的血红素加氧酶-1（HO-1）/脂联素轴来改善内皮功能障碍。
雄性C57BL/6小鼠喂食高脂饮食（HFD），并接受或不接受鸢尾素治疗。测定有无PVAT（PVAT+或PVAT-）时胸主动脉的内皮依赖性血管舒张功能。采用蛋白质免疫印迹法测定PVAT中HO-1和脂联素的水平。通过实时聚合酶链反应检测PVAT中解偶联蛋白1（UCP-1）、细胞死亡诱导DFFA样效应因子A（Cidea）和肿瘤坏死因子-α（TNF-α）的基因表达。
PVAT的存在显著损害了HFD小鼠的内皮功能。用鸢尾素治疗HFD小鼠可显著恢复这种损害，并在体内或体外改善内皮功能。用来自HFD小鼠的PVAT条件培养基（CM）孵育主动脉环（PVAT-）会损害对照小鼠的内皮功能。用来自鸢尾素处理的HFD小鼠的PVAT-CM孵育主动脉环（PVAT-）可防止这种损害。然而，在存在HO-1抑制剂和脂联素受体阻断肽的情况下，有益作用部分减弱。用鸢尾素治疗HFD小鼠可显著增加一氧化氮（NO）生成、HO-1和脂联素的蛋白水平、UCP-1和Cidea的mRNA表达，并降低PVAT中的超氧化物生成和TNF-α表达。
鸢尾素通过调节HFD诱导的肥胖小鼠PVAT中的HO-1/脂联素轴改善内皮功能。这些发现表明，调节PVAT功能可能是鸢尾素改善肥胖中内皮功能的潜在机制。
