Kinin B(1) receptor deficiency leads to leptin hypersensitivity and resistance to obesity

Kinin B(1) receptor deficiency leads to leptin hypersensitivity and resistance to obesity

Autor Mori, Marcelo A Autor UNIFESP Google Scholar
Araujo, Ronaldo de Carvalho Autor UNIFESP Google Scholar
Reis, Felipe Castellani Gomes dos Autor UNIFESP Google Scholar
Sgai, Daniela G. Google Scholar
Fonseca, Raphael Gomes Autor UNIFESP Google Scholar
Barros, Carlos C. Google Scholar
Merino, Vanessa Ferreira Autor UNIFESP Google Scholar
Passadore, Mariana Autor UNIFESP Google Scholar
Barbosa, Ana Maria Autor UNIFESP Google Scholar
Ferrari, Bernard Google Scholar
Carayon, Pierre Google Scholar
Castro, Charlles Heldan de Moura Autor UNIFESP Google Scholar
Shimuta, Suma Imura Autor UNIFESP Google Scholar
Luz, Jacqueline Autor UNIFESP Google Scholar
Bascands, Jean-Loup Google Scholar
Schanstra, Joost P. Google Scholar
Even, Patrick C. Google Scholar
Oliveira, Suzana M. Autor UNIFESP Google Scholar
Bader, Michael Autor UNIFESP Google Scholar
Pesquero, João Bosco Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Univ Mogi das Cruzes
Sanofi Aventis
Inst Natl Sante & Rech Med
Univ Toulouse 3
Inst Natl Rech Agron AgroParisTech
Max Delbruck Ctr Mol Med
Resumo OBJECTIVE-Kinins mediate pathophysiological processes related to hypertension, pain, and inflammation through the activation of two G-protein-coupled receptors, named B(1) and B(2). Although these peptides have been related to glucose homeostasis, their effects on energy balance are still unknown.RESEARCH DESIGN and METHODS-Using genetic and pharmacological strategies to abrogate the kinin B(1) receptor in different animal models of obesity, here we present evidence of a novel role for kinins in the regulation of satiety and adiposity.RESULTS-Kinin B(1) receptor deficiency in mice (B(1)(-/-)) resulted in less fat content, hypoleptinemia, increased leptin sensitivity, and robust protection against high-fat diet-induced weight gain. Under high-fat diet, B(1)(-/-) also exhibited reduced food intake, improved lipid oxidation, and increased energy expenditure. Surprisingly, B(1) receptor deficiency was not able to decrease food intake and adiposity in obese mice lacking leptin (ob/ob-B(1)(-/-)). However, ob/ob-B(1)(-/-) mice were more responsive to the effects of exogenous leptin on body weight and food intake, suggesting that B(1) receptors may be dependent on leptin to display their metabolic roles. Finally, inhibition of weight gain and food intake by B(1) receptor ablation was pharmacologically confirmed by long-term administration of the kinin B(1) receptor antagonist SSR240612 to mice under high-fat diet.CONCLUSIONS-Our data suggest that kinin B(1) receptors participate in the regulation of the energy balance via a mechanism that could involve the modulation of leptin sensitivity.
Idioma Inglês
Data 2008-06-01
Publicado em Diabetes. Alexandria: Amer Diabetes Assoc, v. 57, n. 6, p. 1491-1500, 2008.
ISSN 0012-1797 (Sherpa/Romeo, fator de impacto)
Editor Amer Diabetes Assoc
Extensão 1491-1500
Fonte http://dx.doi.org/10.2337/db07-1508
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000256611600010
URI http://repositorio.unifesp.br/handle/11600/30684

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