Deletion of the Angiotensin Type 2 Receptor (AT2R) Reduces Adipose Cell Size and Protects From Diet-Induced Obesity and Insulin Resistance

  1. Laurent Yvan-Charvet1,
  2. Patrick Even2,
  3. May Bloch-Faure3,
  4. Michèle Guerre-Millo1,
  5. Naima Moustaid-Moussa4,
  6. Pascal Ferre1 and
  7. Annie Quignard-Boulange1
  1. 1Unit 465, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France
  2. 2UMR914, Institut National de la Recherche Agronomique, INAPG, Paris, France
  3. 3Unit 367, INSERM, Paris, France
  4. 4Department of Nutrition and Agricultural Experiment Station, University of Tennessee, Knoxville, Tennessee
  1. Address correspondence and reprint requests to Annie Quignard-Boulange, INSERM U465, 15 rue de l’Ecole de Médecine, 75270 Paris Cedex 06, France. E-mail: quignard{at}


The renin-angiotensin system with its active metabolite angiotensin (Ang) II has been related not only to hypertension but also to obesity and insulin resistance. Recent evidence obtained in vitro suggests that the type 2 Ang II receptor (AT2R) mediates the trophic action of Ang II on adipocyte differentiation and lipogenesis. We used AT2Ry/− mice to delineate a potential role of AT2R in adipose tissue development and metabolism. AT2Ry/− mice had a normal adiposity but displayed a striking adipose tissue phenotype characterized by small adipocytes and an increase in cell number. In muscle, the expression of several genes involved in lipid metabolism, including fatty acid translocase, uncoupling protein-3, peroxisome proliferator–activated receptors (α, δ), and carnitine palmitoyl transferase-1, was increased in AT2R-deficient mice. In response to high-fat feeding, these mice were protected against obesity and obesity-related glucose intolerance, as assessed by glucose tolerance tests. Moreover, lipid oxidation assessed by indirect calorimetry was higher in AT2R-deficient mice than in wild-type mice, irrespective of the diet. This suggests that AT2R-dependent signaling exerts a direct or indirect negative control on lipid utilization in muscles. These data support the idea that AT2R-dependent Ang II signaling increases adipose cell mass and glucose intolerance and thus could participate to the deleterious effects of a high-fat diet.


    • Accepted January 2, 2005.
    • Received September 27, 2004.
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