This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Yvan-Charvet, L. Articles by Quignard-Boulangé, A. Search for Related Content PubMed PubMed Citation Articles by Yvan-Charvet, L. Articles by Quignard-Boulangé, A.

Deficiency of Angiotensin Type 2 Receptor Rescues Obesity But Not Hypertension Induced by Overexpression of Angiotensinogen in Adipose Tissue

Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 872 (L.Y.-C., A.Q.-B.), and Université Pierre et Marie Curie (L.Y.-C., A.Q.-B.), Paris 6 Unité Mixte de Recherche 872, Centre Biomédical des Cordeliers, Paris F-75006, France; Institute of Signaling, Developmental Biology, and Cancer Research (F.M., G.A., M.T.), Centre National de la Recherche Scientifique, Université de Nice Sophia-Antipolis, 06100 Nice, France; INSERM Unité 833 (N.L., J.-M.G.), College de France, Paris F-75005, France; and Department of Animal Science and The University of Tennessee Obesity Research Center (N.M.-M.), The University of Tennessee Institute of Agriculture, Knoxville, Tennessee 37996

Address all correspondence and requests for reprints to: Annie Quignard-Boulangé, Unité Mixte de Recherche 914 Institut National de la Recherche Agronomique-AgroParisTech, 16 rue Claude Bernard, 75005 Paris, France. E-mail: quignard{at}agroparistech.fr.

Increased angiotensinogen (AGT) production by white adipose tissue has been related to not only obesity but also hypertension. Several studies have highlighted the importance of the angiotensin II type 2 receptor (AT2) in the regulation of blood pressure and fat mass, but the relevance of this transporter in a physiopathological model of increased AGT production, as it occurs in obesity, has not yet been investigated. We used transgenic mice that display either a deletion of AT2 (AT2 KO), an overexpression of AGT (OVEX), or both compound mutants (KOVEX). Results demonstrated that adipocyte hypertrophy and increased lipogenic gene expression induced by adipose AGT overproduction was rescued by deletion of AT2. In line with AGT overexpression, KOVEX and OVEX mice have similar increased plasma AGT levels. However, KOVEX mice display a higher blood pressure than OVEX mice. In kidney, renin expression was clearly reduced in OVEX mice, and its expression was normalized in KOVEX mice. Taken together, we demonstrated that the loss of AT2 expression was sufficient to rescue obesity induced by adipose tissue AGT overexpression and confirmed the necessary role of AT2 for the onset of obesity in this model. Furthermore, despite a reduction of adipose mass in KOVEX, AT2 deficiency caused increased renin production, further worsening the hypertension caused by AGT overexpression.