title: Blockade of Angiotensin II type-1 receptor reduces oxidative stress in adipose tissue and ameliorates adipocytokine dysregulation.
abstract: 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.
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kurata
authors.forename: H
authors.initials: H
authors.lastname: Nishizawa
authors.forename: S
authors.initials: S
authors.lastname: Kihara
authors.forename: N
authors.initials: N
authors.lastname: Maeda
authors.forename: M
authors.initials: M
authors.lastname: Sonoda
authors.forename: T
authors.initials: T
authors.lastname: Okada
authors.forename: K
authors.initials: K
authors.lastname: Ohashi
authors.forename: T
authors.initials: T
authors.lastname: Hibuse
authors.forename: K
authors.initials: K
authors.lastname: Fujita
authors.forename: A
authors.initials: A
authors.lastname: Yasui
authors.forename: A
authors.initials: A
authors.lastname: Hiuge
authors.forename: M
authors.initials: M
authors.lastname: Kumada
authors.forename: H
authors.initials: H
authors.lastname: Kuriyama
authors.forename: I
authors.initials: I
authors.lastname: Shimomura
authors.forename: T
authors.initials: T
authors.lastname: Funahashi
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000804:Angiotensin II / Q000502:physiology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D050197:Atherosclerosis / Q000503:physiopathology / Q000517:prevention & control; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D007093:Imidazoles / Q000494:pharmacology*; D007674:Kidney Diseases / Q000503:physiopathology / Q000517:prevention & control; D024821:Metabolic Syndrome / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D052242:Adiponectin; D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C076498:Saa3 protein, mouse; D000685:Serum Amyloid A Protein; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; C437965:olmesartan