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

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dc.contributor.authorMori, Marcelo A [UNIFESP]
dc.contributor.authorAraujo, Ronaldo de Carvalho [UNIFESP]
dc.contributor.authorReis, Felipe Castellani Gomes dos [UNIFESP]
dc.contributor.authorSgai, Daniela G.
dc.contributor.authorFonseca, Raphael Gomes [UNIFESP]
dc.contributor.authorBarros, Carlos C.
dc.contributor.authorMerino, Vanessa Ferreira [UNIFESP]
dc.contributor.authorPassadore, Mariana [UNIFESP]
dc.contributor.authorBarbosa, Ana Maria [UNIFESP]
dc.contributor.authorFerrari, Bernard
dc.contributor.authorCarayon, Pierre
dc.contributor.authorCastro, Charlles Heldan de Moura [UNIFESP]
dc.contributor.authorShimuta, Suma Imura [UNIFESP]
dc.contributor.authorLuz, Jacqueline [UNIFESP]
dc.contributor.authorBascands, Jean-Loup
dc.contributor.authorSchanstra, Joost P.
dc.contributor.authorEven, Patrick C.
dc.contributor.authorOliveira, Suzana M. [UNIFESP]
dc.contributor.authorBader, Michael [UNIFESP]
dc.contributor.authorPesquero, João Bosco [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Mogi das Cruzes
dc.contributor.institutionSanofi Aventis
dc.contributor.institutionInst Natl Sante & Rech Med
dc.contributor.institutionUniv Toulouse 3
dc.contributor.institutionInst Natl Rech Agron AgroParisTech
dc.contributor.institutionMax Delbruck Ctr Mol Med
dc.date.accessioned2016-01-24T13:51:24Z
dc.date.available2016-01-24T13:51:24Z
dc.date.issued2008-06-01
dc.description.abstractOBJECTIVE-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.en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, Brazil
dc.description.affiliationUniv Mogi das Cruzes, Mogi Das Cruzes, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Physiol, BR-04023062 São Paulo, Brazil
dc.description.affiliationSanofi Aventis, Montpellier, France
dc.description.affiliationUniversidade Federal de São Paulo, Dept Med, BR-04023062 São Paulo, Brazil
dc.description.affiliationInst Natl Sante & Rech Med, Dept Renal & Cardiac Remodeling, U858 I2MR, Toulouse, France
dc.description.affiliationUniv Toulouse 3, Inst Med Mol Rangueil, F-31062 Toulouse, France
dc.description.affiliationInst Natl Rech Agron AgroParisTech, UMR914 Nutr Physiol & Ingest Behav, Paris, France
dc.description.affiliationMax Delbruck Ctr Mol Med, Berlin, Germany
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Physiol, BR-04023062 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Med, BR-04023062 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent1491-1500
dc.identifierhttp://dx.doi.org/10.2337/db07-1508
dc.identifier.citationDiabetes. Alexandria: Amer Diabetes Assoc, v. 57, n. 6, p. 1491-1500, 2008.
dc.identifier.doi10.2337/db07-1508
dc.identifier.issn0012-1797
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/30684
dc.identifier.wosWOS:000256611600010
dc.language.isoeng
dc.publisherAmer Diabetes Assoc
dc.relation.ispartofDiabetes
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleKinin B(1) receptor deficiency leads to leptin hypersensitivity and resistance to obesityen
dc.typeinfo:eu-repo/semantics/article
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