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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 the adipose tissue mRNA expression of proinflammatory cytokines ((a) MCP-1; (b) TNF-α; (c) IL-6; and (d) PAI-1) in KKAy mice. The values are the mean ± SEM (n = 8). *P < 0.05, **P < 0.01 versus C57BL/6 (ANOVA). Olm indicates olmesartan.
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fig6: Effects of olmesartan (olm) on the adipose tissue mRNA expression of proinflammatory cytokines ((a) MCP-1; (b) TNF-α; (c) IL-6; and (d) PAI-1) in KKAy mice. The values are the mean ± SEM (n = 8). *P < 0.05, **P < 0.01 versus C57BL/6 (ANOVA). Olm indicates olmesartan.

Mentions: Regarding the expression of tissue inflammatory cytokines (MCP-1, TNF-α, IL-6, and PAI-1) in adipose tissue (Figure 6), while the PAI-1 mRNA expression was not altered in the vehicle-treated KKAy mice (Figure 6(d)), the mRNA levels of MCP-1, TNF-α, and IL-6 were all significantly upregulated in the KKAy mice treated with vehicle compared with the control C57BL/6 mice (MCP-1 and TNF-α, P < 0.01; IL-6, P < 0.05 versus C57BL/6) (Figures 6(a), 6(b), and 6(c)). With respect to a possible effect of olmesartan on these inflammatory cytokine genes in the adipose tissue, the KKAy mice treated with olmesartan exhibited a blunted increase in adipose IL-6 mRNA expression (Figure 6(c)), in spite of the fact that there are no effects on the adipose MCP-1, TNF-α, and PAI-1 mRNA expression (Figures 6(a), 6(b), and 6(d)).


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 the adipose tissue mRNA expression of proinflammatory cytokines ((a) MCP-1; (b) TNF-α; (c) IL-6; and (d) PAI-1) in KKAy mice. The values are the mean ± SEM (n = 8). *P < 0.05, **P < 0.01 versus C57BL/6 (ANOVA). Olm indicates olmesartan.
© Copyright Policy
Related In: Results  -  Collection

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

fig6: Effects of olmesartan (olm) on the adipose tissue mRNA expression of proinflammatory cytokines ((a) MCP-1; (b) TNF-α; (c) IL-6; and (d) PAI-1) in KKAy mice. The values are the mean ± SEM (n = 8). *P < 0.05, **P < 0.01 versus C57BL/6 (ANOVA). Olm indicates olmesartan.
Mentions: Regarding the expression of tissue inflammatory cytokines (MCP-1, TNF-α, IL-6, and PAI-1) in adipose tissue (Figure 6), while the PAI-1 mRNA expression was not altered in the vehicle-treated KKAy mice (Figure 6(d)), the mRNA levels of MCP-1, TNF-α, and IL-6 were all significantly upregulated in the KKAy mice treated with vehicle compared with the control C57BL/6 mice (MCP-1 and TNF-α, P < 0.01; IL-6, P < 0.05 versus C57BL/6) (Figures 6(a), 6(b), and 6(c)). With respect to a possible effect of olmesartan on these inflammatory cytokine genes in the adipose tissue, the KKAy mice treated with olmesartan exhibited a blunted increase in adipose IL-6 mRNA expression (Figure 6(c)), in spite of the fact that there are no effects on the adipose MCP-1, TNF-α, and PAI-1 mRNA expression (Figures 6(a), 6(b), and 6(d)).

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