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Int. J. Mol. Sci. 2017, 18(3), 676; doi:10.3390/ijms18030676

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

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.
Academic Editors: Anastasia Susie Mihailidou, Jan Danser, Sadayoshi Ito, Fumitoshi Satoh and Akira Nishiyama
Received: 28 January 2017 / Revised: 9 March 2017 / Accepted: 16 March 2017 / Published: 21 March 2017
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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. View Full-Text
Keywords: Cre/loxP; angiotensin; receptor; adipocyte; obesity Cre/loxP; angiotensin; receptor; adipocyte; obesity
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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. 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.

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