Effects of Ang II receptor blocker irbesartan on adipose tissue function in mice with metabolic disorders.
Recent studies indicate that the functional renin-angiotensin system (RAS) exists in the adipose tissue. The adipose tissue RAS is proposed in the pathophysiology of metabolic disorders. In the present study, we examined therapeutic effects of irbesartan, an angiotensin II (Ang II) type 1 receptor (AT1R)-specific blocker, in genetically obese diabetic KKAy mice, a model of human metabolic disorders without any dietary loading, with our focus on the analysis on possible effect of irbesartan on the adipose tissue. The treatment with irbesartan significantly lowered systolic blood pressure with a concomitant decrease in body weight in KKAy mice. In addition, irbesartan significantly decreased the adipose leptin mRNA expression and tended to decrease IL-6 mRNA expression in the adipose tissue of KKAy mice. Furthermore irbesartan preserved the adipose gene expression of AT1R-associated protein (ATRAP), an endogenous inhibitory molecule of tissue AT1R signaling, with a concomitant tendency of up-regulation of adipose tissue ATRAP/AT1R ratio. Collectively, these results suggest that the irbesartan-induced beneficial suppressive effect on the leptin-IL-6 axis in the adipose tissue in KKAy mice is partly mediated by a trend of up-regulation of the adipose ATRAP/AT1R ratio as one of pleiotropic effects of irbesartan.
1. Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate Scholl of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Akinobu
A
Maeda
1. Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate Scholl of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Kouichi
K
Tamura
1. Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate Scholl of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Hiromichi
H
Wakui
1. Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate Scholl of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Masato
M
Ohsawa
1. Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate Scholl of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Kengo
K
Azushima
1. Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate Scholl of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Kazushi
K
Uneda
1. Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate Scholl of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Ryu
R
Kobayashi
1. Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate Scholl of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Yuko
Y
Tsurumi-Ikeya
1. Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate Scholl of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Tomohiko
T
Kanaoka
1. Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate Scholl of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Toru
T
Dejima
1. Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate Scholl of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Koji
K
Ohki
1. Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate Scholl of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Sona
S
Haku
2. Department of Molecular Biology, Yokohama City University Graduate Scholl of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Akio
A
Yamashita
1. Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate Scholl of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Satoshi
S
Umemura
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis; D000273:Adipose Tissue / Q000187:drug effects*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D006801:Humans; D000077405:Irbesartan; D020738:Leptin / Q000096:biosynthesis; D051379:Mice; D009765:Obesity / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013777:Tetrazoles / Q000008:administration & dosage*
D048868:Adaptor Proteins, Signal Transducing; C119712:Agtrap protein, mouse; D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D020738:Leptin; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000077405:Irbesartan
adipose tissue; inflammation; metabolic disorders; receptor; renin-angiotensin system.