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Angiotensinogen-Deficient Mice Exhibit Impairment of Diet-Induced Weight Gain with Alteration in Adipose Tissue Development and Increased Locomotor Activity

Centre National de la Recherche Scientifique 6543, Centre de Biochimie (F.M., P.S.-M., R.N., G.A., M.T.), Nice 06108, France; University Medical Center, Department of Physiology, Faculty of Medicine (J.S.), Genève, 1211, Switzerland; INSERM, U-352, Institut National des Sciences Appliquées (A.G.), Villeurbanne 69100, France; INSERM, U-465 (A.Q.-B., S.T.), Paris 75270, France; and University of Tsukuba (A.F.), Tsukuba, Ibaraki 305, Japan

Address all correspondence and requests for reprints to: Dr. Gérard Ailhaud, Centre de Biochimie, UMR 6543, Centre National de la Recherche Scientifique, Université de Nice-Sophia Antipolis, Faculté des Sciences, Parc Valrose, 06108 Nice Cedex 2, France.

White adipose tissue is known to contain the components of the renin-angiotensin system, which gives rise to angiotensin II from angiotensinogen (AGT). Recent evidence obtained in vitro and ex vivo is in favor of angiotensin II acting as a trophic factor of adipose tissue development. To determine whether AGT plays a role in vivo in this process, comparative studies were performed in AGT-deficient (agt^-/-) mice and control wild-type mice. The results showed that agt^-/- mice gain less weight than wild-type mice in response to a chow or high fat diet. Adipose tissue mass from weaning to adulthood appeared altered rather specifically, as both the size and the weight of other organs were almost unchanged. Food intake was similar for both genotypes, suggesting a decreased metabolic efficiency in agt^-/- mice. Consistent with this hypothesis, cellularity measurement indicated hypotrophy of adipocytes in agt^-/- mice with a parallel decrease in the fatty acid synthase activity. Moreover, AGT-deficient mice exhibited a significantly increased locomotor activity, whereas metabolic rate and mRNA levels of uncoupling proteins remained similar in both genotypes. Thus, AGT appears to be involved in the regulation of fat mass through a combination of decreased lipogenesis and increased locomotor activity that may be centrally mediated.

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