Limits...
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.

Show MeSH

Related in: MedlinePlus

Effects of olmesartan (olm) on systolic blood pressure (a), heart rate (b), and body weight (c) in KKAy mice. Individual values are shown in the graphs and the values are also shown as the mean ± SEM (n = 8). B, before treatment; A, after treatment. *P < 0.05, **P < 0.01 versus before treatment; ##P < 0.01 versus KKAy + vehicle; ‡P < 0.01 versus C57BL/6 (ANOVA).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4060760&req=5

fig1: Effects of olmesartan (olm) on systolic blood pressure (a), heart rate (b), and body weight (c) in KKAy mice. Individual values are shown in the graphs and the values are also shown as the mean ± SEM (n = 8). B, before treatment; A, after treatment. *P < 0.05, **P < 0.01 versus before treatment; ##P < 0.01 versus KKAy + vehicle; ‡P < 0.01 versus C57BL/6 (ANOVA).

Mentions: The systolic blood pressure, heart rate, and body weight at baseline and after the study period in the control C57BL/6, vehicle-treated KKAy, and olmesartan-treated KKAy mice are shown in Figure 1. At baseline there were no significant differences in systolic blood pressure or heart rate between the groups before the treatment. Body weight at baseline was significantly greater in the KKAy mice of either treatment group than in the control C57BL/6 mice (P < 0.01 versus C57BL/6). With respect to the effects of treatment with olmesartan at a dose of 3 mg/kg per day for 4 weeks on heart rate and body weight, heart rate was not affected in the KKAy mice by the treatment with olmesartan for 4 weeks compared with baseline (baseline versus 4 weeks, 720 ± 11 versus 729 ± 8 bpm, NS), and there was a significant increase in body weight after the olmesartan treatment (baseline versus 4 weeks, 41.2 ± 0.4 versus 47.5 ± 0.8 g, P < 0.01). After 4 weeks, heart rate and body weight did not differ significantly between the vehicle-treated and olmesartan-treated KKAy mice (Figure 1).


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 systolic blood pressure (a), heart rate (b), and body weight (c) in KKAy mice. Individual values are shown in the graphs and the values are also shown as the mean ± SEM (n = 8). B, before treatment; A, after treatment. *P < 0.05, **P < 0.01 versus before treatment; ##P < 0.01 versus KKAy + vehicle; ‡P < 0.01 versus C57BL/6 (ANOVA).
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Effects of olmesartan (olm) on systolic blood pressure (a), heart rate (b), and body weight (c) in KKAy mice. Individual values are shown in the graphs and the values are also shown as the mean ± SEM (n = 8). B, before treatment; A, after treatment. *P < 0.05, **P < 0.01 versus before treatment; ##P < 0.01 versus KKAy + vehicle; ‡P < 0.01 versus C57BL/6 (ANOVA).
Mentions: The systolic blood pressure, heart rate, and body weight at baseline and after the study period in the control C57BL/6, vehicle-treated KKAy, and olmesartan-treated KKAy mice are shown in Figure 1. At baseline there were no significant differences in systolic blood pressure or heart rate between the groups before the treatment. Body weight at baseline was significantly greater in the KKAy mice of either treatment group than in the control C57BL/6 mice (P < 0.01 versus C57BL/6). With respect to the effects of treatment with olmesartan at a dose of 3 mg/kg per day for 4 weeks on heart rate and body weight, heart rate was not affected in the KKAy mice by the treatment with olmesartan for 4 weeks compared with baseline (baseline versus 4 weeks, 720 ± 11 versus 729 ± 8 bpm, NS), and there was a significant increase in body weight after the olmesartan treatment (baseline versus 4 weeks, 41.2 ± 0.4 versus 47.5 ± 0.8 g, P < 0.01). After 4 weeks, heart rate and body weight did not differ significantly between the vehicle-treated and olmesartan-treated KKAy mice (Figure 1).

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