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Leptin regulates ACE activity in mice

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Abstract

Leptin is a hormone related to metabolism. It also influences blood pressure, but the mechanisms triggered in this process are not yet elucidated. Angiotensin-I converting enzyme (ACE) regulates cardiovascular functions and recently has been associated with metabolism control and obesity. Here, we used ob/ob mice, a model lacking leptin, to answer the question whether ACE and leptin could interact to influence blood pressure, thereby linking the renin-angiotensin system and obesity. These mice are obese and diabetic but have normal 24 h mean arterial pressure. Our results show that plasma and lung ACE activities as well as ACE mRNA expression were significantly decreased in ob/ob mice. In agreement with these findings, the hypotensive effect produced by enalapril administration was attenuated in the obese mice. Plasma renin, angiotensinogen, angiotensin I, bradykinin, and angiotensin 1–7 were increased, whereas plasma angiotensin II concentration was unchanged in obese mice. Chronic infusion of leptin increased renin activity and angiotensin II concentration in both groups and increased ACE activity in ob/ob mice. Acute leptin infusion restored ACE activity in leptin-deficient mice. Moreover, the effect of an ACE inhibitor on blood pressure was not changed in ob/+ mice during leptin treatment but increased four times in obese mice. In summary, our findings show that the renin–angiotensin system is altered in ob/ob mice, with markedly reduced ACE activity, which suggests a possible connection between the renin–angiotensin system and leptin. These results point to an important interplay between the angiotensinergic and the leptinergic systems, which may play a role in the pathogenesis of obesity, hypertension, and metabolic syndrome.

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Acknowledgments

We are grateful to Wolf-Eberhard Siems and Nils Dietrich for their help in measuring ACE activity.

Sources of funding

This work was supported by Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), the Deutsche Akademische Austauschdienst (DAAD/PROBRAL), and the Deutsche Forschungsgemeinschaft (BA 1374/16-1).

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Authors and Affiliations

  1. Department of Biophysics, Escola Paulista de Medicina, Federal University of São Paulo, 04023-062, São Paulo, SP, Brazil

    Aline Mourao Hilzendeger, Rafael Leite Morais, Ronaldo Carvalho Araujo, Clovis Ryuichi Nakaie, Adriana Karaoglanovic Carmona & João Bosco Pesquero

  2. Max-Delbrück-Center for Molecular Medicine (MDC), Berlin, Germany

    Aline Mourao Hilzendeger, Mihail Todiras, Ralph Plehm, Andrey da Costa Goncalves, Fatimunnisa Qadri, Volkmar Gross & Michael Bader

  3. Experimental and Clinical Research Center (ECRC) at the Max-Delbrück-Center for Molecular Medicine (MDC), Berlin, Germany

    Andrey da Costa Goncalves, Fatimunnisa Qadri & Volkmar Gross

  4. Nephrology Division, Department of Medicine, Escola Paulista de Medicina, Federal University of Sao Paulo, São Paulo, SP, Brazil

    Dulce Elena Casarini

Authors
  1. Aline Mourao Hilzendeger
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  2. Rafael Leite Morais
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  3. Mihail Todiras
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  4. Ralph Plehm
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  5. Andrey da Costa Goncalves
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  9. Clovis Ryuichi Nakaie
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  10. Dulce Elena Casarini
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  11. Adriana Karaoglanovic Carmona
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  12. Michael Bader
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  13. João Bosco Pesquero
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Correspondence to João Bosco Pesquero.

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Hilzendeger, A.M., Morais, R.L., Todiras, M. et al. Leptin regulates ACE activity in mice. J Mol Med 88, 899–907 (2010). https://doi.org/10.1007/s00109-010-0649-7

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  • DOI: https://doi.org/10.1007/s00109-010-0649-7

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