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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 adipocyte hypertrophy in KKAy mice. Upper panel: histological analysis of epididymal adipose tissue sections ((a) C57BL/6; (b) KKAy + vehicle; (c) KKAy + olmesartan) stained with hematoxylin and eosin in each experimental group. Original magnification: ×200. Lower panel: adipocyte diameter (d) and area (e). The values are the mean ± SEM (n = 8). **P < 0.01 versus C57BL/6; ##P < 0.01 versus KKAy + vehicle (ANOVA). Olm indicates olmesartan.
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fig3: Effects of olmesartan (olm) on adipocyte hypertrophy in KKAy mice. Upper panel: histological analysis of epididymal adipose tissue sections ((a) C57BL/6; (b) KKAy + vehicle; (c) KKAy + olmesartan) stained with hematoxylin and eosin in each experimental group. Original magnification: ×200. Lower panel: adipocyte diameter (d) and area (e). The values are the mean ± SEM (n = 8). **P < 0.01 versus C57BL/6; ##P < 0.01 versus KKAy + vehicle (ANOVA). Olm indicates olmesartan.

Mentions: We examined whether there was any phenotypic alteration in the adipose tissue of the KKAy mice treated with olmesartan. Although the KKAy mice treated with vehicle had significantly larger adipocytes than the control C57BL/6 mice (P < 0.01 versus C57BL/6) (Figures 3(a), 3(b), and 3(c)), adipocyte hypertrophy was significantly inhibited in the KKAy mice treated with olmesartan for 4 weeks (Figure 3(d); vehicle-treated KKAy mice versus olmesartan-treated KKAy mice; diameter: 113.7 ± 3.7 versus 91.2 ± 3.1 μm, P < 0.01; Figure 3(e), area: 11131 ± 765 versus 7264 ± 415 μm2, P < 0.01).


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 adipocyte hypertrophy in KKAy mice. Upper panel: histological analysis of epididymal adipose tissue sections ((a) C57BL/6; (b) KKAy + vehicle; (c) KKAy + olmesartan) stained with hematoxylin and eosin in each experimental group. Original magnification: ×200. Lower panel: adipocyte diameter (d) and area (e). The values are the mean ± SEM (n = 8). **P < 0.01 versus C57BL/6; ##P < 0.01 versus KKAy + vehicle (ANOVA). Olm indicates olmesartan.
© Copyright Policy
Related In: Results  -  Collection

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

fig3: Effects of olmesartan (olm) on adipocyte hypertrophy in KKAy mice. Upper panel: histological analysis of epididymal adipose tissue sections ((a) C57BL/6; (b) KKAy + vehicle; (c) KKAy + olmesartan) stained with hematoxylin and eosin in each experimental group. Original magnification: ×200. Lower panel: adipocyte diameter (d) and area (e). The values are the mean ± SEM (n = 8). **P < 0.01 versus C57BL/6; ##P < 0.01 versus KKAy + vehicle (ANOVA). Olm indicates olmesartan.
Mentions: We examined whether there was any phenotypic alteration in the adipose tissue of the KKAy mice treated with olmesartan. Although the KKAy mice treated with vehicle had significantly larger adipocytes than the control C57BL/6 mice (P < 0.01 versus C57BL/6) (Figures 3(a), 3(b), and 3(c)), adipocyte hypertrophy was significantly inhibited in the KKAy mice treated with olmesartan for 4 weeks (Figure 3(d); vehicle-treated KKAy mice versus olmesartan-treated KKAy mice; diameter: 113.7 ± 3.7 versus 91.2 ± 3.1 μm, P < 0.01; Figure 3(e), area: 11131 ± 765 versus 7264 ± 415 μm2, P < 0.01).

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