ATRAP Expression in Brown Adipose Tissue Does Not Influence the Development of Diet-Induced Metabolic Disorders in Mice.
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 usingAdipoq-Cre. Using these mice, we examined the functional role of adipose ATRAP in the pathogenesis of obesity-related metabolic disorders. Compared with ATRAPfl/flmice, ATRAPadipoqmice 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/flmice showed decreased endogenous ATRAP expression in WAT that was equivalent to ATRAPadipoqmice, 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.
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. t146017e@yokohama-cu.ac.jp.
Kohji
K
Ohki
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. hiro1234@yokohama-cu.ac.jp.
Hiromichi
H
Wakui
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. azushima@yokohama-cu.ac.jp.|Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore. azushima@yokohama-cu.ac.jp.
Kengo
K
Azushima
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. k_uneda@yokohama-cu.ac.jp.
Kazushi
K
Uneda
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. t106048f@yokohama-cu.ac.jp.
Sona
S
Haku
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. t136034d@yokohama-cu.ac.jp.
Ryu
R
Kobayashi
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. kspring00712@gmail.com.
Kotaro
K
Haruhara
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. ja472t@bma.biglobe.ne.jp.
Sho
S
Kinguchi
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. mmatsuda@yokohama-cu.ac.jp.
Miyuki
M
Matsuda
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. o.masato@gmail.com.
Masato
M
Ohsawa
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. maeda_chigasaki@yahoo.co.jp.
Akinobu
A
Maeda
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. minegish@yokohama-cu.ac.jp.
Shintaro
S
Minegishi
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. tommmish@yokohama-cu.ac.jp.
Tomoaki
T
Ishigami
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. ystoya@yokohama-cu.ac.jp.
Yoshiyuki
Y
Toya
Department of Molecular Biology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. yamasita@yokohama-cu.ac.jp.
Akio
A
Yamashita
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. umemuras@med.yokohama-cu.ac.jp.|Yokohama Rosai Hospital, 3211 Kozukue-cho, Kohoku-ku, Yokohama 222-0036, Japan. umemuras@med.yokohama-cu.ac.jp.
Satoshi
S
Umemura
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. tamukou@med.yokohama-cu.ac.jp.
Kouichi
K
Tamura
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D005947:Glucose / Q000378:metabolism; D050356:Lipid Metabolism; D008659:Metabolic Diseases / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009765:Obesity / Q000150:complications / Q000209:etiology / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C119712:Agtrap protein, mouse; D005947:Glucose
Cre/loxP; adipocyte; angiotensin; obesity; receptor