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Effects of the Angiotensin receptor blocker olmesartan on adipocyte hypertrophy and function in mice with metabolic disorders.

Maeda A, Tamura K, Wakui H, Ohsawa M, Azushima K, Uneda K, Kanaoka T, Kobayashi R, Ohki K, Matsuda M, Tsurumi-Ikeya Y, Yamashita A, Tokita Y, Umemura S - Biomed Res Int (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.

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.

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Effects of olmesartan (olm) on daily food intake in KKAy mice. The values are the mean ± SEM (n = 8). **P < 0.01 versus C57BL/6 (ANOVA).
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fig2: Effects of olmesartan (olm) on daily food intake in KKAy mice. The values are the mean ± SEM (n = 8). **P < 0.01 versus C57BL/6 (ANOVA).

Mentions: On the other hand, systolic blood pressure in the KKAy mice was significantly decreased by the olmesartan treatment for 4 weeks compared with baseline (baseline versus 4 weeks; 108 ± 3 versus 95 ± 3 mmHg, P < 0.01), and systolic blood pressure was significantly lower in the KKAy mice treated with olmesartan than those treated with vehicle (P < 0.01 versus vehicle) (Figure 1). Furthermore, although the daily food intake after 4 weeks was significantly greater in the KKAy mice of either treatment group than the control C57BL/6 mice (P < 0.01 versus C57BL/6), the daily food intake was similar in the vehicle-treated and olmesartan-treated KKAy mice groups (Figure 2).


Effects of the Angiotensin receptor blocker olmesartan on adipocyte hypertrophy and function in mice with metabolic disorders.

Maeda A, Tamura K, Wakui H, Ohsawa M, Azushima K, Uneda K, Kanaoka T, Kobayashi R, Ohki K, Matsuda M, Tsurumi-Ikeya Y, Yamashita A, Tokita Y, Umemura S - Biomed Res Int (2014)

Effects of olmesartan (olm) on daily food intake in KKAy mice. The values are the mean ± SEM (n = 8). **P < 0.01 versus C57BL/6 (ANOVA).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4060760&req=5

fig2: Effects of olmesartan (olm) on daily food intake in KKAy mice. The values are the mean ± SEM (n = 8). **P < 0.01 versus C57BL/6 (ANOVA).
Mentions: On the other hand, systolic blood pressure in the KKAy mice was significantly decreased by the olmesartan treatment for 4 weeks compared with baseline (baseline versus 4 weeks; 108 ± 3 versus 95 ± 3 mmHg, P < 0.01), and systolic blood pressure was significantly lower in the KKAy mice treated with olmesartan than those treated with vehicle (P < 0.01 versus vehicle) (Figure 1). Furthermore, although the daily food intake after 4 weeks was significantly greater in the KKAy mice of either treatment group than the control C57BL/6 mice (P < 0.01 versus C57BL/6), the daily food intake was similar in the vehicle-treated and olmesartan-treated KKAy mice groups (Figure 2).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.

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.

Show MeSH
Related in: MedlinePlus