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

作者：Ohki Kohji; Wakui Hiromichi; Azushima Kengo; Uneda Kazushi; Haku Sona; Kobayashi Ryu; Haruhara Kotaro; Kinguchi Sho; Matsuda Miyuki; Ohsawa Masato; Maeda Akinobu; Minegishi Shintaro; Ishigami Tomoaki; Toya Yoshiyuki; Yamashita Akio; Umemura Satoshi; Tamura Kouichi

来源：International Journal of Molecular Sciences, 2017, 18(3): 676.

DOI：10.3390/ijms18030676

• Cre/loxP
• angiotensin
• receptor
• adipocyte
• obesity

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 ATRAP(fl/fl) mice, ATRAP(adipoq) 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, ATRAP(fl/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.

• 出版日期2017-3