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Title: Leptin regulates ACE activity in mice
Authors: Hilzendeger, Aline Mourão [UNIFESP]
Morais, Rafael Leite [UNIFESP]
Todiras, Mihail
Plehm, Ralph
Goncalves, Andrey da Costa
Qadri, Fatimunnisa
Araujo, Ronaldo Carvalho [UNIFESP]
Gross, Volkmar
Nakaie, Clovis Ryuichi [UNIFESP]
Casarini, Dulce Elena
Carmona, Adriana Karaoglanovic [UNIFESP]
Bader, Michael
Pesquero, Joao Bosco [UNIFESP]
Universidade Federal de São Paulo (UNIFESP)
Max Delbruck Ctr Mol Med MDC
Keywords: Renin-angiotensin system
ob/ob mice
Angiotensin-I converting enzyme
Issue Date: 1-Sep-2010
Publisher: Springer
Citation: Journal of Molecular Medicine-jmm. New York: Springer, v. 88, n. 9, p. 899-907, 2010.
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.
ISSN: 0946-2716
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