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Article

ATRAP Expression in Brown Adipose Tissue Does Not Influence the Development of Diet-Induced Metabolic Disorders in Mice

by
Kohji Ohki
1,
Hiromichi Wakui
1,*,
Kengo Azushima
1,2,*,
Kazushi Uneda
1,
Sona Haku
1,
Ryu Kobayashi
1,
Kotaro Haruhara
1,
Sho Kinguchi
1,
Miyuki Matsuda
1,
Masato Ohsawa
1,
Akinobu Maeda
1,
Shintaro Minegishi
1,
Tomoaki Ishigami
1,
Yoshiyuki Toya
1,
Akio Yamashita
3,
Satoshi Umemura
1,4 and
Kouichi Tamura
1,*
1
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3–9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan
2
Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore
3
Department of Molecular Biology, Yokohama City University Graduate School of Medicine, 3–9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan
4
Yokohama Rosai Hospital, 3211 Kozukue-cho, Kohoku-ku, Yokohama 222-0036, Japan
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2017, 18(3), 676; https://doi.org/10.3390/ijms18030676
Submission received: 28 January 2017 / Revised: 9 March 2017 / Accepted: 16 March 2017 / Published: 21 March 2017
(This article belongs to the Special Issue Selected Papers from the Renin–Angiotensin–Aldosterone System (RAAS)2016: Official Satellite of ISH2016, from September 23 to 24 in Tokyo, Japan)
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Abstract

Activation of tissue renin–angiotensin system (RAS), mainly mediated by an angiotensin II (Ang II) type 1 receptor (AT1R), plays an important role in the development of obesity-related metabolic disorders. We have shown that AT1R-associated protein (ATRAP), a specific binding protein of AT1R, functions as an endogenous inhibitor to prevent excessive activation of tissue RAS. In the present study, we newly generated ATRAP/Agtrap-floxed (ATRAPfl/fl) mice and adipose tissue-specific ATRAP downregulated (ATRAPadipoq) mice by the Cre/loxP system using Adipoq-Cre. Using these mice, we examined the functional role of adipose ATRAP in the pathogenesis of obesity-related metabolic disorders. Compared with ATRAPfl/fl mice, ATRAPadipoq mice exhibited a decreased ATRAP expression in visceral white adipose tissue (WAT) and brown adipose tissue (BAT) by approximately 30% and 85%, respectively. When mice were fed a high-fat diet, ATRAPfl/fl mice showed decreased endogenous ATRAP expression in WAT that was equivalent to ATRAPadipoq mice, and there was no difference in the exacerbation of dietary obesity and glucose and lipid metabolism. These results indicate that ATRAP in BAT does not influence the pathogenesis of dietary obesity or metabolic disorders. Future studies that modulate ATRAP in WAT are necessary to assess its in vivo functions in the development of obesity-related metabolic disorders.
Keywords: Cre/loxP; angiotensin; receptor; adipocyte; obesity Cre/loxP; angiotensin; receptor; adipocyte; obesity

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MDPI and ACS Style

Ohki, K.; Wakui, H.; Azushima, K.; Uneda, K.; Haku, S.; Kobayashi, R.; Haruhara, K.; Kinguchi, S.; Matsuda, M.; Ohsawa, M.; et al. ATRAP Expression in Brown Adipose Tissue Does Not Influence the Development of Diet-Induced Metabolic Disorders in Mice. Int. J. Mol. Sci. 2017, 18, 676. https://doi.org/10.3390/ijms18030676

AMA Style

Ohki K, Wakui H, Azushima K, Uneda K, Haku S, Kobayashi R, Haruhara K, Kinguchi S, Matsuda M, Ohsawa M, et al. ATRAP Expression in Brown Adipose Tissue Does Not Influence the Development of Diet-Induced Metabolic Disorders in Mice. International Journal of Molecular Sciences. 2017; 18(3):676. https://doi.org/10.3390/ijms18030676

Chicago/Turabian Style

Ohki, Kohji, Hiromichi Wakui, Kengo Azushima, Kazushi Uneda, Sona Haku, Ryu Kobayashi, Kotaro Haruhara, Sho Kinguchi, Miyuki Matsuda, Masato Ohsawa, and et al. 2017. "ATRAP Expression in Brown Adipose Tissue Does Not Influence the Development of Diet-Induced Metabolic Disorders in Mice" International Journal of Molecular Sciences 18, no. 3: 676. https://doi.org/10.3390/ijms18030676

APA Style

Ohki, K., Wakui, H., Azushima, K., Uneda, K., Haku, S., Kobayashi, R., Haruhara, K., Kinguchi, S., Matsuda, M., Ohsawa, M., Maeda, A., Minegishi, S., Ishigami, T., Toya, Y., Yamashita, A., Umemura, S., & Tamura, K. (2017). ATRAP Expression in Brown Adipose Tissue Does Not Influence the Development of Diet-Induced Metabolic Disorders in Mice. International Journal of Molecular Sciences, 18(3), 676. https://doi.org/10.3390/ijms18030676

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