Blockade of angiotensin II type-1 receptor reduces oxidative stress in adipose tissue and ameliorates adipocytokine dysregulation
Blockade of angiotensin II type-1 receptor reduces oxidative stress in adipose tissue and ameliorates adipocytokine dysregulation
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DOI：
10.1038/sj.ki.5001810
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发表时间：
2006-11-01
影响因子：
19.6
通讯作者：
Funahashi, T.
中科院分区：
文献类型：
--
作者：
Kurata, A.;Nishizawa, H.;Funahashi, T.
脂肪细胞因子的产生失调可能参与代谢综合征中动脉粥样硬化性心血管疾病和与代谢综合征相关的慢性肾脏疾病（CKD）的发展。本研究的目的是确定血管紧张素II（Ang II）1型受体阻滞剂（ARB）治疗对脂肪细胞因子调节的影响。奥美沙坦是一种ARB，可显著减弱遗传性和饮食诱导肥胖小鼠中与年龄和体重相关的血浆脂联素福尔斯下降，而不影响体重，但对瘦小鼠的血浆脂联素水平无影响。奥美沙坦还可改善肥胖症中脂肪细胞因子的失调，如肿瘤坏死因子-α、纤溶酶原激活物抑制剂-1、单核细胞趋化蛋白-1和血清淀粉样蛋白A3。奥美沙坦可显著减少脂肪堆积产生的活性氧，并减弱脂肪组织中烟酰胺腺嘌呤二核苷酸磷酸氢酶氧化酶亚单位的表达。在培养的脂肪细胞中，奥美沙坦作为一种抗氧化剂和改善脂肪细胞因子失调。我们的研究结果表明，血管紧张素II受体的封锁改善脂肪细胞因子失调，这种行动是介导的，至少部分，通过在肥胖脂肪组织的氧化应激为目标。血管紧张素II信号和随后的氧化应激在脂肪组织中可能是潜在的目标，为预防动脉粥样硬化性心血管疾病的代谢综合征，也在代谢综合征为基础的慢性肾脏病。
Dysregulated production of adipocytokines may be involved in the development of atherosclerotic cardiovascular disease in metabolic syndrome and chronic kidney disease ( CKD) associated with metabolic syndrome. The aim of this study was to determine the effects of treatment with angiotensin II ( Ang II) type-1 receptor blocker ( ARB) on the regulation of adipocytokines. Olmesartan, an ARB, significantly blunted the age- and body weight-associated falls in plasma adiponectin both in genetically and diet-induced obese mice, without affecting body weight, but had no effect on plasma adiponectin levels in lean mice. Olmesartan also ameliorated dysregulation of adipocytokines in obesity, such as tumor necrosis factor-alpha, plasminogen activator inhibitor-1, monocyte chemotactic protein-1, and serum amyloid A3. Olmesartan significantly reduced reactive oxygen species originating from accumulated fat and attenuated the expression of nicotinamide adenine dinucleotide phospho hydrogenase oxidase subunits in adipose tissue. In cultured adipocytes, olmesartan acted as an antioxidant and improved adipocytokine dysregulation. Our results indicate that blockade of Ang II receptor ameliorates adipocytokine dysregulation and that such action is mediated, at least in part, by targeting oxidative stress in obese adipose tissue. Ang II signaling and subsequent oxidative stress in adipose tissue may be potential targets for the prevention of atherosclerotic cardiovascular disease in metabolic syndrome and also in metabolic syndrome-based CKD.