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

International Journal of Molecular Sciences

Hiromichi Wakui¹  Masato Ohsawa¹  Kohji Ohki¹  Ryu Kobayashi¹  Kazushi Uneda¹  Kouichi Tamura¹  Kotaro Haruhara¹  Miyuki Matsuda¹  Sho Kinguchi¹  Kengo Azushima¹  Shintaro Minegishi¹  Sona Haku¹  Tomoaki Ishigami¹  Akinobu Maeda¹  Yoshiyuki Toya¹  Satoshi Umemura¹  Akio Yamashita² 

[1] Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3–9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan;Department of Molecular Biology, Yokohama City University Graduate School of Medicine, 3–9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan;

关键词: Cre/loxP;    angiotensin;    receptor;    adipocyte;    obesity;   

DOI  :  10.3390/ijms18030676

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown