Attenuation of diet-induced weight gain and adiposity through increased energy expenditure in mice lacking angiotensin II type 1a receptor

Ryuji Kouyama, Takayoshi Suganami, Junko Nishida, Miyako Tanaka, Takuya Toyoda, Minako Kiso, Tsuyoshi Chiwata, Yoshihiro Miyamoto, Yasunao Yoshimasa, Akiyoshi Fukamizu, Masatsugu Horiuchi, Yukio Hirata, Yoshihiro Ogawa

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Given that angiotensin II (AII) type 1 and 2 receptors (Agtr1 and Agtr2) are expressed in adipose tissue, AII may act directly on adipose tissue. However, regardless of whether AII directly modulates adipose tissue growth and metabolism in vivo and, if so, whether it is mediated via Agtr1 are still matters of debate. To understand the functional role of Agtr1 in adipose tissue growth and metabolism in vivo, we examined the metabolic phenotypes of mice lacking Agtr1a (Agtr1a -/- mice) during a high-fat diet. The Agtr1a -/- mice exhibited the attenuation of diet-induced body weight gain and adiposity, and insulin resistance relative to wild-type littermates (Agtr1a +/+ mice). They also showed increased energy expenditure accompanied by sympathetic activation, as revealed by increased rectal temperature and oxygen consumption, increased expression of uncoupling protein-1 mRNA in brown adipose tissue, and increased urinary catecholamine excretion. The heterozygous Agtr1a-deficient mice (Agtr1a +/- mice) also exhibited metabolic phenotypes similar to those of Agtr1a -/- mice. Using mouse embryonic fibroblasts derived from Agtr1a +/+ and Agtr1a -/- mice, we found no significant difference between genotypes in the ability to differentiate into lipid-laden mature adipocytes. In primary cultures of mouse mature adipocytes, AII increased the expression of mRNAs for some adipocytokines, which was abolished by pharmacological blockade of Agtr1. This study demonstrates that Agtr1a -/- mice exhibit attenuation of diet-induced weight gain and adiposity through increased energy expenditure. The data also suggest that AII does not affect directly adipocyte differentiation, but can modulate adipocytokine production via Agtr1.

Original languageEnglish
Pages (from-to)3481-3489
Number of pages9
Issue number8
Publication statusPublished - Aug 1 2005
Externally publishedYes


All Science Journal Classification (ASJC) codes

  • Endocrinology

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