Adipose tissue-specific dysregulation of angiotensinogen by oxidative stress in obesity.
Adipose tissue-specific dysregulation of angiotensinogen by oxidative stress in obesity.
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DOI：
10.1016/j.metabol.2009.11.016
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发表时间：
2010-09
影响因子：
9.8
通讯作者：
Nakao, Kazuwa
中科院分区：
文献类型：
--
作者：
Okada, Sadanori;Kozuka, Chisayo;Masuzaki, Hiroaki;Yasue, Shintaro;Ishii-Yonemoto, Takako;Tanaka, Tomohiro;Yamamoto, Yuji;Noguchi, Michio;Kusakabe, Toru;Tomita, Tsutomu;Fujikura, Junji;Ebihara, Ken;Hosoda, Kiminori;Sakaue, Hiroshi;Kobori, Hiroyuki;Ham, Mira;Lee, Yun Sok;Kim, Jae Bum;Saito, Yoshihiko;Nakao, Kazuwa
脂肪组织表达肾素-血管紧张素系统的所有成分，包括血管紧张素原（AGT）。最近的研究强调了 AGT 在脂肪组织功能和体内平衡中的潜在作用。然而，围绕肥胖脂肪组织中 AGT 的调节机制存在一些争议。在此背景下，我们证明，与非肥胖受试者相比，肥胖受试者皮下脂肪组织中的 AGT 信使 RNA (mRNA) 水平显着降低。与瘦同窝小鼠相比，肥胖小鼠的脂肪组织 AGT mRNA 水平也较低；然而，肝脏 AGT mRNA 水平保持不变。当3T3-L1脂肪细胞长期培养时，脂肪细胞变得肥大，活性氧的产生显着增加。在脂肪细胞肥大过程中，AGT的表达和分泌持续减少。用活性氧（过氧化氢）或肿瘤坏死因子α处理3T3-L1和原代脂肪细胞导致AGT的表达和分泌显着减少。另一方面，用抗氧化剂N-乙酰半胱氨酸处理可抑制肥大的3T3-L1脂肪细胞中AGT表达和分泌的减少。最后，用 N-乙酰半胱氨酸治疗肥胖 db/db 小鼠可增加脂肪组织中 AGT 的表达，但不会增加肝脏中的 AGT 表达。本研究首次证明氧化应激使肥胖脂肪组织中的 AGT 失调，为肥胖病理生理学中 AGT 调节与氧化应激之间的脂肪组织特异性相互作用提供了新的见解。
Adipose tissue expresses all components of the renin-angiotensin system including angiotensinogen (AGT). Recent studies have highlighted a potential role of AGT in adipose tissue function and homeostasis. However, some controversies surround the regulatory mechanisms of AGT in obese adipose tissue. In this context, we here demonstrated that the AGT messenger RNA (mRNA) level in human subcutaneous adipose tissue was significantly reduced in obese subjects as compared with nonobese subjects. Adipose tissue AGT mRNA level in obese mice was also lower as compared with their lean littermates; however, the hepatic AGT mRNA level remained unchanged. When 3T3-L1 adipocytes were cultured for a long period, the adipocytes became hypertrophic with a marked increase in the production of reactive oxygen species. Expression and secretion of AGT continued to decrease during the course of adipocyte hypertrophy. Treatment of the 3T3-L1 and primary adipocytes with reactive oxygen species (hydrogen peroxide) or tumor necrosis factor α caused a significant decrease in the expression and secretion of AGT. On the other hand, treatment with the antioxidant N-acetyl cysteine suppressed the decrease in the expression and secretion of AGT in the hypertrophied 3T3-L1 adipocytes. Finally, treatment of obese db/db mice with N-acetyl cysteine augmented the expression of AGT in the adipose tissue, but not in the liver. The present study demonstrates for the first time that oxidative stress dysregulates AGT in obese adipose tissue, providing a novel insight into the adipose tissue–specific interaction between the regulation of AGT and oxidative stress in the pathophysiology of obesity.
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影响因子：
8.3
作者：
Engeli, S;Bohnke, J;Sharma, AM
通讯作者：
Sharma, AM
DOI：
10.1152/ajpregu.1997.273.1.r236
发表时间：
1997-07-01
影响因子：
2.8
作者：
Jones, BH;Standridge, MK;Moustaid, N
通讯作者：
Moustaid, N
影响因子：
37.8
作者：
Flesch, M;Höper, A;Mann, DL
通讯作者：
Mann, DL
影响因子：
--
作者：
Lee, Yun Sok;Kim, A. Young;Kim, Jae Bum
通讯作者：
Kim, Jae Bum
影响因子：
20.1
作者：
GRIENDLING, KK;MINIERI, CA;ALEXANDER, RW
通讯作者：
ALEXANDER, RW