Kinin B1 and B2 receptor deficiency protects against obesity induced by a high-fat diet and improves glucose tolerance in mice

Rafael L Morais,1 Elton D Silva,1 Vicência M Sales,1 Rafael Filippelli-Silva,1 Marcelo A Mori,1 Michael Bader,2 João B Pesquero1 1Department of Biophysics, Universidade Federal de São Paulo, São Paulo, Brazil; 2Max-Delbrück Center for Molecular Med...

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Autores principales:	Morais RL, Silva ED, Sales VM, Filippelli-Silva R, Mori MA, Bader M, Pesquero JB
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/b3ea330d21f346439a5ee231547f3d83
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spelling	oai:doaj.org-article:b3ea330d21f346439a5ee231547f3d832021-12-02T00:07:08ZKinin B1 and B2 receptor deficiency protects against obesity induced by a high-fat diet and improves glucose tolerance in mice1178-7007https://doaj.org/article/b3ea330d21f346439a5ee231547f3d832015-08-01T00:00:00Zhttp://www.dovepress.com/kinin-b1-and-b2-receptor-deficiency-protects-against-obesity-induced-b-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Rafael L Morais,1 Elton D Silva,1 Vicência M Sales,1 Rafael Filippelli-Silva,1 Marcelo A Mori,1 Michael Bader,2 João B Pesquero1 1Department of Biophysics, Universidade Federal de São Paulo, São Paulo, Brazil; 2Max-Delbrück Center for Molecular Medicine, Berlin, Germany Abstract: The kallikrein-kinin system is well known for its role in pain and inflammation, and has been shown recently by our group to have a role also in the regulation of energy expenditure. We have demonstrated that B1 receptor knockout (B1KO) mice are resistant to obesity induced by a high-fat diet (HFD) and that B1 receptor expression in adipocytes regulates glucose tolerance and predisposition to obesity. However, it is also known that in the absence of B1 receptor, the B2 receptor is overexpressed and can take over the function of its B1 counterpart, rendering uncertain the role of each kinin receptor in these metabolic effects. Therefore, we investigated the impact of ablation of each kinin receptor on energy metabolism using double kinin receptor knockout (B1B2KO) mice. Our data show that B1B2KO mice were resistant to HFD-induced obesity, with lower food intake and feed efficiency when compared with wild-type mice. They also had lower blood insulin and leptin levels and higher glucose tolerance after treatment with an HFD. Gene expression for tumor necrosis factor-alpha and C-reactive protein, which are important genes for insulin resistance, was reduced in white adipose tissue, skeletal muscle, and the liver in B1B2KO mice after the HFD. In summary, our data show that disruption of kinin B1 and B2 receptors has a profound impact on metabolic homeostasis in mice, by improving glucose tolerance and preventing HFD-induced obesity. These novel findings could pave the way for development of new pharmacological strategies to treat metabolic disorders such as insulin resistance and obesity. Keywords: kallikrein-kinin system, B1/B2 receptors, obesity, glucose tolerance, insulin resistanceMorais RLSilva EDSales VMFilippelli-Silva RMori MABader MPesquero JBDove Medical PressarticleSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol 2015, Iss default, Pp 399-407 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Specialties of internal medicine RC581-951
spellingShingle	Specialties of internal medicine RC581-951 Morais RL Silva ED Sales VM Filippelli-Silva R Mori MA Bader M Pesquero JB Kinin B1 and B2 receptor deficiency protects against obesity induced by a high-fat diet and improves glucose tolerance in mice
description	Rafael L Morais,1 Elton D Silva,1 Vicência M Sales,1 Rafael Filippelli-Silva,1 Marcelo A Mori,1 Michael Bader,2 João B Pesquero1 1Department of Biophysics, Universidade Federal de São Paulo, São Paulo, Brazil; 2Max-Delbrück Center for Molecular Medicine, Berlin, Germany Abstract: The kallikrein-kinin system is well known for its role in pain and inflammation, and has been shown recently by our group to have a role also in the regulation of energy expenditure. We have demonstrated that B1 receptor knockout (B1KO) mice are resistant to obesity induced by a high-fat diet (HFD) and that B1 receptor expression in adipocytes regulates glucose tolerance and predisposition to obesity. However, it is also known that in the absence of B1 receptor, the B2 receptor is overexpressed and can take over the function of its B1 counterpart, rendering uncertain the role of each kinin receptor in these metabolic effects. Therefore, we investigated the impact of ablation of each kinin receptor on energy metabolism using double kinin receptor knockout (B1B2KO) mice. Our data show that B1B2KO mice were resistant to HFD-induced obesity, with lower food intake and feed efficiency when compared with wild-type mice. They also had lower blood insulin and leptin levels and higher glucose tolerance after treatment with an HFD. Gene expression for tumor necrosis factor-alpha and C-reactive protein, which are important genes for insulin resistance, was reduced in white adipose tissue, skeletal muscle, and the liver in B1B2KO mice after the HFD. In summary, our data show that disruption of kinin B1 and B2 receptors has a profound impact on metabolic homeostasis in mice, by improving glucose tolerance and preventing HFD-induced obesity. These novel findings could pave the way for development of new pharmacological strategies to treat metabolic disorders such as insulin resistance and obesity. Keywords: kallikrein-kinin system, B1/B2 receptors, obesity, glucose tolerance, insulin resistance
format	article
author	Morais RL Silva ED Sales VM Filippelli-Silva R Mori MA Bader M Pesquero JB
author_facet	Morais RL Silva ED Sales VM Filippelli-Silva R Mori MA Bader M Pesquero JB
author_sort	Morais RL
title	Kinin B1 and B2 receptor deficiency protects against obesity induced by a high-fat diet and improves glucose tolerance in mice
title_short	Kinin B1 and B2 receptor deficiency protects against obesity induced by a high-fat diet and improves glucose tolerance in mice
title_full	Kinin B1 and B2 receptor deficiency protects against obesity induced by a high-fat diet and improves glucose tolerance in mice
title_fullStr	Kinin B1 and B2 receptor deficiency protects against obesity induced by a high-fat diet and improves glucose tolerance in mice
title_full_unstemmed	Kinin B1 and B2 receptor deficiency protects against obesity induced by a high-fat diet and improves glucose tolerance in mice
title_sort	kinin b1 and b2 receptor deficiency protects against obesity induced by a high-fat diet and improves glucose tolerance in mice
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/b3ea330d21f346439a5ee231547f3d83
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Kinin B1 and B2 receptor deficiency protects against obesity induced by a high-fat diet and improves glucose tolerance in mice

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