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Kinin B1 receptor deficiency leads to leptin hypersensitivity and resistance to obesity

Item Type:Article
Title:Kinin B1 receptor deficiency leads to leptin hypersensitivity and resistance to obesity
Creators Name:Mori, M.A. and Araújo, R.C. and Reis, F.C. and Sgai, D.G. and Fonseca, R.G. and Barros, C.C. and Merino, V.F. and Passadore, M. and Barbosa, A.M. and Ferrari, B. and Carayon, P. and Castro, C.H. and Shimuta, S.I. and Luz, J. and Bascands, J.L. and Schanstra, J.P. and Even, P.C. and Oliveira, S.M. and Bader, M. and Pesquero, J.B.
Abstract: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, we present here 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 (HFD)-induced weight gain. Under HFD, 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 HFD. 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.
Keywords:Adipose Tissue, Body Composition, Indirect Calorimetry, Dietary Fats, Leptin, Obesity, Bradykinin B1 Receptor, Animals, Mice
Publisher:American Diabetes Association
Page Range:1491-1500
Date:June 2008
Official Publication:https://doi.org/10.2337/db07-1508
PubMed:View item in PubMed

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