Adipose tissue-specific dysregulation of angiotensinogen by oxidative stress in obesity

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

来源：Metabolism-Clinical and Experimental, 2010, 59(9): 1241-1251.

DOI：10.1016/j.metabol.2009.11.016

Adipose tissue expresses all components of the renin-angiotensin system including angiotensinogen (ACT) Recent studies have highlighted a potential role of ACT in adipose tissue function and homeostasis. However, some controversies surround the regulatory mechanisms of ACT in obese adipose tissue In this context, we here demonstrated that the ACT 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 ACT 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 ACT 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 alpha caused a significant decrease in the expression and secretion of ACT. On the other hand, treatment with the antioxidant N-acetyl cysteine suppressed the decrease in the expression and secretion of ACT in the hypertrophied 3T3-L1 adipocytes Finally, treatment of obese db/db mice with N-acetyl cysteine augmented the expression of ACT in the adipose tissue, but not in the liver The present study demonstrates for the first time that oxidative stress dysregulates ACT in obese adipose tissu

• 出版日期2010-9