Agtr1a deficiency in mice attenuated diet-induced weight gain, adiposity, and insulin resistance through increased energy expenditure compared to wild-type littermates.
Does genetic deletion of the angiotensin II type 1a receptor attenuate diet-induced weight gain and adiposity in mice?
Genetic deletion of the angiotensin II type 1a receptor in mice attenuates diet-induced weight gain and adiposity by increasing energy expenditure.
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.
Kouyama et al. (Sat,) conducted a other in Diet-induced weight gain and adiposity. Agtr1a deficiency vs. Wild-type littermates (Agtr1a+/+) was evaluated on Diet-induced body weight gain, adiposity, and insulin resistance. Agtr1a deficiency in mice attenuated diet-induced weight gain, adiposity, and insulin resistance through increased energy expenditure compared to wild-type littermates.
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