Adipose tissue-specific dysregulation of angiotensinogen by oxidative stress in obesity.
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 alpha 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.
Okada
Sadanori
S
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
Kozuka
Chisayo
C
Masuzaki
Hiroaki
H
Yasue
Shintaro
S
Ishii-Yonemoto
Takako
T
Tanaka
Tomohiro
T
Yamamoto
Yuji
Y
Noguchi
Michio
M
Kusakabe
Toru
T
Tomita
Tsutomu
T
Fujikura
Junji
J
Ebihara
Ken
K
Hosoda
Kiminori
K
Sakaue
Hiroshi
H
Kobori
Hiroyuki
H
Ham
Mira
M
Lee
Yun Sok
YS
Kim
Jae Bum
JB
Saito
Yoshihiko
Y
Nakao
Kazuwa
K
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000328:Adult; D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D048429:Cell Size; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008820:Mice, Obese; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050151:Subcutaneous Fat / Q000378:metabolism* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D000808:Angiotensinogen