Cargando…

Effects of the Angiotensin Receptor Blocker Olmesartan on Adipocyte Hypertrophy and Function in Mice with Metabolic Disorders

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Maeda, Akinobu, Tamura, Kouichi, Wakui, Hiromichi, Ohsawa, Masato, Azushima, Kengo, Uneda, Kazushi, Kanaoka, Tomohiko, Kobayashi, Ryu, Ohki, Kohji, Matsuda, Miyuki, Tsurumi-Ikeya, Yuko, Yamashita, Akio, Tokita, Yasuo, Umemura, Satoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4060760/
https://www.ncbi.nlm.nih.gov/pubmed/24991574
http://dx.doi.org/10.1155/2014/946492
_version_ 1782321405556162560
author Maeda, Akinobu
Tamura, Kouichi
Wakui, Hiromichi
Ohsawa, Masato
Azushima, Kengo
Uneda, Kazushi
Kanaoka, Tomohiko
Kobayashi, Ryu
Ohki, Kohji
Matsuda, Miyuki
Tsurumi-Ikeya, Yuko
Yamashita, Akio
Tokita, Yasuo
Umemura, Satoshi
author_facet Maeda, Akinobu
Tamura, Kouichi
Wakui, Hiromichi
Ohsawa, Masato
Azushima, Kengo
Uneda, Kazushi
Kanaoka, Tomohiko
Kobayashi, Ryu
Ohki, Kohji
Matsuda, Miyuki
Tsurumi-Ikeya, Yuko
Yamashita, Akio
Tokita, Yasuo
Umemura, Satoshi
author_sort Maeda, Akinobu
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4060760
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Hindawi Publishing Corporation
record_format MEDLINE/PubMed
spelling pubmed-40607602014-07-02 Effects of the Angiotensin Receptor Blocker Olmesartan on Adipocyte Hypertrophy and Function in Mice with Metabolic Disorders Maeda, Akinobu Tamura, Kouichi Wakui, Hiromichi Ohsawa, Masato Azushima, Kengo Uneda, Kazushi Kanaoka, Tomohiko Kobayashi, Ryu Ohki, Kohji Matsuda, Miyuki Tsurumi-Ikeya, Yuko Yamashita, Akio Tokita, Yasuo Umemura, Satoshi Biomed Res Int Research Article 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. Hindawi Publishing Corporation 2014 2014-06-02 /pmc/articles/PMC4060760/ /pubmed/24991574 http://dx.doi.org/10.1155/2014/946492 Text en Copyright © 2014 Akinobu Maeda et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Maeda, Akinobu
Tamura, Kouichi
Wakui, Hiromichi
Ohsawa, Masato
Azushima, Kengo
Uneda, Kazushi
Kanaoka, Tomohiko
Kobayashi, Ryu
Ohki, Kohji
Matsuda, Miyuki
Tsurumi-Ikeya, Yuko
Yamashita, Akio
Tokita, Yasuo
Umemura, Satoshi
Effects of the Angiotensin Receptor Blocker Olmesartan on Adipocyte Hypertrophy and Function in Mice with Metabolic Disorders
title Effects of the Angiotensin Receptor Blocker Olmesartan on Adipocyte Hypertrophy and Function in Mice with Metabolic Disorders
title_full Effects of the Angiotensin Receptor Blocker Olmesartan on Adipocyte Hypertrophy and Function in Mice with Metabolic Disorders
title_fullStr Effects of the Angiotensin Receptor Blocker Olmesartan on Adipocyte Hypertrophy and Function in Mice with Metabolic Disorders
title_full_unstemmed Effects of the Angiotensin Receptor Blocker Olmesartan on Adipocyte Hypertrophy and Function in Mice with Metabolic Disorders
title_short Effects of the Angiotensin Receptor Blocker Olmesartan on Adipocyte Hypertrophy and Function in Mice with Metabolic Disorders
title_sort effects of the angiotensin receptor blocker olmesartan on adipocyte hypertrophy and function in mice with metabolic disorders
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4060760/
https://www.ncbi.nlm.nih.gov/pubmed/24991574
http://dx.doi.org/10.1155/2014/946492
work_keys_str_mv AT maedaakinobu effectsoftheangiotensinreceptorblockerolmesartanonadipocytehypertrophyandfunctioninmicewithmetabolicdisorders
AT tamurakouichi effectsoftheangiotensinreceptorblockerolmesartanonadipocytehypertrophyandfunctioninmicewithmetabolicdisorders
AT wakuihiromichi effectsoftheangiotensinreceptorblockerolmesartanonadipocytehypertrophyandfunctioninmicewithmetabolicdisorders
AT ohsawamasato effectsoftheangiotensinreceptorblockerolmesartanonadipocytehypertrophyandfunctioninmicewithmetabolicdisorders
AT azushimakengo effectsoftheangiotensinreceptorblockerolmesartanonadipocytehypertrophyandfunctioninmicewithmetabolicdisorders
AT unedakazushi effectsoftheangiotensinreceptorblockerolmesartanonadipocytehypertrophyandfunctioninmicewithmetabolicdisorders
AT kanaokatomohiko effectsoftheangiotensinreceptorblockerolmesartanonadipocytehypertrophyandfunctioninmicewithmetabolicdisorders
AT kobayashiryu effectsoftheangiotensinreceptorblockerolmesartanonadipocytehypertrophyandfunctioninmicewithmetabolicdisorders
AT ohkikohji effectsoftheangiotensinreceptorblockerolmesartanonadipocytehypertrophyandfunctioninmicewithmetabolicdisorders
AT matsudamiyuki effectsoftheangiotensinreceptorblockerolmesartanonadipocytehypertrophyandfunctioninmicewithmetabolicdisorders
AT tsurumiikeyayuko effectsoftheangiotensinreceptorblockerolmesartanonadipocytehypertrophyandfunctioninmicewithmetabolicdisorders
AT yamashitaakio effectsoftheangiotensinreceptorblockerolmesartanonadipocytehypertrophyandfunctioninmicewithmetabolicdisorders
AT tokitayasuo effectsoftheangiotensinreceptorblockerolmesartanonadipocytehypertrophyandfunctioninmicewithmetabolicdisorders
AT umemurasatoshi effectsoftheangiotensinreceptorblockerolmesartanonadipocytehypertrophyandfunctioninmicewithmetabolicdisorders