title: Effects of the Angiotensin receptor blocker olmesartan on adipocyte hypertrophy and function in mice with metabolic disorders.
abstract: In the present study, we examined the therapeutic effects of olmesartan, an angiotensin II (Ang II) type 1 receptor (AT1R)-specific blocker, in genetically obese diabetic KKAy mice, a model of human metabolic disorders with visceral obesity, with a focus on an olmesartan effect on the adipose tissue. Olmesartan treatment (3 mg/kg per day) for 4 weeks significantly lowered systolic blood pressure but did not affect body weight during the study period in KKAy mice. However, there were three interesting findings possibly related to the pleiotropic effects of olmesartan on adipose tissue in KKAy mice: (1) an inhibitory effect on adipocyte hypertrophy, (2) a suppressive effect on IL-6 gene expression, and (3) an ameliorating effect on oxidative stress. On the other hand, olmesartan exerted no evident influence on the adipose tissue expression of AT1R-associated protein (ATRAP), which is a molecule interacting with AT1R so as to inhibit pathological AT1R activation and is suggested to be an emerging molecular target in metabolic disorders with visceral obesity. Collectively, these results suggest that the blood pressure lowering effect of olmesartan in KKAy mice is associated with an improvement in adipocyte, including suppression of adipocyte hypertrophy and inhibition of the adipose IL-6-oxidative stress axis. Further study is needed to clarify the functional role of adipose ATRAP in the pleiotropic effects of olmesartan.
authors.affiliation: Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Maeda
authors.affiliation: Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Kouichi
authors.identifier: 0000-0002-0660-5372
authors.initials: K
authors.lastname: Tamura
authors.affiliation: Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Wakui
authors.affiliation: Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Ohsawa
authors.affiliation: Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Azushima
authors.affiliation: Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Kazushi
authors.initials: K
authors.lastname: Uneda
authors.affiliation: Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Kanaoka
authors.affiliation: Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Ryu
authors.initials: R
authors.lastname: Kobayashi
authors.affiliation: Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Ohki
authors.affiliation: Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Matsuda
authors.affiliation: Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tsurumi-Ikeya
authors.affiliation: Department of Molecular Biology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Yamashita
authors.affiliation: Renal Division, Department of Medicine, Fujisawa Municipal Hospital, 2-6-1 Fujisawa, Fujisawa 251-8550, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tokita
authors.affiliation: Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Umemura
mesh_terms: D017667:Adipocytes / Q000187:drug effects; D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006984:Hypertrophy / Q000188:drug therapy / Q000473:pathology; D007093:Imidazoles / Q000008:administration & dosage*; D015850:Interleukin-6 / Q000096:biosynthesis; D008659:Metabolic Diseases / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051379:Mice; D056128:Obesity, Abdominal / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D013777:Tetrazoles / Q000008:administration & dosage*
chemical_list: D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D015850:Interleukin-6; D013777:Tetrazoles; C437965:olmesartan