title: Adipose tissue-specific dysregulation of angiotensinogen by oxidative stress in obesity.
abstract: 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.
authors.affiliation: Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
authors.forename: Sadanori
authors.initials: S
authors.lastname: Okada
authors.forename: Chisayo
authors.initials: C
authors.lastname: Kozuka
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Masuzaki
authors.forename: Shintaro
authors.initials: S
authors.lastname: Yasue
authors.forename: Takako
authors.initials: T
authors.lastname: Ishii-Yonemoto
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tanaka
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Michio
authors.initials: M
authors.lastname: Noguchi
authors.forename: Toru
authors.initials: T
authors.lastname: Kusakabe
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tomita
authors.forename: Junji
authors.initials: J
authors.lastname: Fujikura
authors.forename: Ken
authors.initials: K
authors.lastname: Ebihara
authors.forename: Kiminori
authors.initials: K
authors.lastname: Hosoda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakaue
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobori
authors.forename: Mira
authors.initials: M
authors.lastname: Ham
authors.forename: Yun Sok
authors.initials: YS
authors.lastname: Lee
authors.forename: Jae Bum
authors.initials: JB
authors.lastname: Kim
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Saito
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
mesh_terms: 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
chemical_list: D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D000808:Angiotensinogen