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

• Published in: Endocrinology (Philadelphia) 2009-03, Vol.150 (3), p.1421-1428
• Main Authors: Yvan-Charvet, Laurent, Massiéra, Florence, Lamandé, Noël, Ailhaud, Gérard, Teboul, Michèle, Moustaid-Moussa, Naima, Gasc, Jean-Marie, Quignard-Boulangé, Annie
• Format: Article
• Language: English
• Subjects: Adipose tissue; Adipose Tissue - cytology; Adipose Tissue - metabolism; Adiposity - genetics; Angiotensin AT2 receptors; Angiotensin II; Angiotensinogen; Angiotensinogen - genetics; Angiotensinogen - metabolism; Animals; Antihypertensives; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood pressure; Body fat; Body Weight - genetics; Cardiology. Vascular system; Cell Count; Cells, Cultured; Deletion; Experimental diseases; Female; Fundamental and applied biological sciences. Psychology; Gene deletion; Gene expression; Genotype; Hypertension; Hypertension - genetics; Hypertension - metabolism; Hypertrophy; Lipogenesis - genetics; Male; Medical sciences; Metabolic diseases; Mice; Mice, Inbred C57BL; Mice, Transgenic; Obesity; Obesity - genetics; Obesity - metabolism; Receptor, Angiotensin, Type 2 - genetics; Receptors; Renin; Transgenic mice; Vertebrates: endocrinology
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2008-1120

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. Angiotensin type 2 receptor shows antihypertensive function but promotes the angiotensin II-mediated fat mass enlargement.