Deletion of inducible nitric-oxide synthase in leptin-deficient mice improves brown adipose tissue function.

<h4>Background</h4>Leptin and nitric oxide (NO) on their own participate in the control of non-shivering thermogenesis. However, the functional interplay between both factors in this process has not been explored so far. Therefore, the aim of the present study was to analyze the impact o...

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Autores principales:	Sara Becerril, Amaia Rodríguez, Victoria Catalán, Neira Sáinz, Beatriz Ramírez, María Collantes, Iván Peñuelas, Javier Gómez-Ambrosi, Gema Frühbeck
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d271b2f1b06c40f59d87128a4ac2c93e
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spelling	oai:doaj.org-article:d271b2f1b06c40f59d87128a4ac2c93e2021-12-02T20:21:10ZDeletion of inducible nitric-oxide synthase in leptin-deficient mice improves brown adipose tissue function.1932-620310.1371/journal.pone.0010962https://doaj.org/article/d271b2f1b06c40f59d87128a4ac2c93e2010-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20532036/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Leptin and nitric oxide (NO) on their own participate in the control of non-shivering thermogenesis. However, the functional interplay between both factors in this process has not been explored so far. Therefore, the aim of the present study was to analyze the impact of the absence of the inducible NO synthase (iNOS) gene in the regulation of energy balance in ob/ob mice.<h4>Methods and findings</h4>Double knockout (DBKO) mice simultaneously lacking the ob and iNOS genes were generated, and the expression of molecules involved in the control of brown fat cell function was analyzed by real-time PCR, western-blot and immunohistochemistry. Twelve week-old DBKO mice exhibited reduced body weight (p<0.05), decreased amounts of total fat pads (p<0.05), lower food efficiency rates (p<0.05) and higher rectal temperature (p<0.05) than ob/ob mice. Ablation of iNOS also improved the carbohydrate and lipid metabolism of ob/ob mice. DBKO showed a marked reduction in the size of brown adipocytes compared to ob/ob mutants. In this sense, in comparison to ob/ob mice, DBKO rodents showed an increase in the expression of PR domain containing 16 (Prdm16), a transcriptional regulator of brown adipogenesis. Moreover, iNOS deletion enhanced the expression of mitochondria-related proteins, such as peroxisome proliferator-activated receptor gamma coactivator-1 alpha (Pgc-1alpha), sirtuin-1 (Sirt-1) and sirtuin-3 (Sirt-3). Accordingly, mitochondrial uncoupling proteins 1 and 3 (Ucp-1 and Ucp-3) were upregulated in brown adipose tissue (BAT) of DBKO mice as compared to ob/ob rodents.<h4>Conclusion</h4>Ablation of iNOS improved the energy balance of ob/ob mice by decreasing food efficiency through an increase in thermogenesis. These effects may be mediated, in part, through the recovery of the BAT phenotype and brown fat cell function improvement.Sara BecerrilAmaia RodríguezVictoria CatalánNeira SáinzBeatriz RamírezMaría CollantesIván PeñuelasJavier Gómez-AmbrosiGema FrühbeckPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 6, p e10962 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sara Becerril Amaia Rodríguez Victoria Catalán Neira Sáinz Beatriz Ramírez María Collantes Iván Peñuelas Javier Gómez-Ambrosi Gema Frühbeck Deletion of inducible nitric-oxide synthase in leptin-deficient mice improves brown adipose tissue function.
description	<h4>Background</h4>Leptin and nitric oxide (NO) on their own participate in the control of non-shivering thermogenesis. However, the functional interplay between both factors in this process has not been explored so far. Therefore, the aim of the present study was to analyze the impact of the absence of the inducible NO synthase (iNOS) gene in the regulation of energy balance in ob/ob mice.<h4>Methods and findings</h4>Double knockout (DBKO) mice simultaneously lacking the ob and iNOS genes were generated, and the expression of molecules involved in the control of brown fat cell function was analyzed by real-time PCR, western-blot and immunohistochemistry. Twelve week-old DBKO mice exhibited reduced body weight (p<0.05), decreased amounts of total fat pads (p<0.05), lower food efficiency rates (p<0.05) and higher rectal temperature (p<0.05) than ob/ob mice. Ablation of iNOS also improved the carbohydrate and lipid metabolism of ob/ob mice. DBKO showed a marked reduction in the size of brown adipocytes compared to ob/ob mutants. In this sense, in comparison to ob/ob mice, DBKO rodents showed an increase in the expression of PR domain containing 16 (Prdm16), a transcriptional regulator of brown adipogenesis. Moreover, iNOS deletion enhanced the expression of mitochondria-related proteins, such as peroxisome proliferator-activated receptor gamma coactivator-1 alpha (Pgc-1alpha), sirtuin-1 (Sirt-1) and sirtuin-3 (Sirt-3). Accordingly, mitochondrial uncoupling proteins 1 and 3 (Ucp-1 and Ucp-3) were upregulated in brown adipose tissue (BAT) of DBKO mice as compared to ob/ob rodents.<h4>Conclusion</h4>Ablation of iNOS improved the energy balance of ob/ob mice by decreasing food efficiency through an increase in thermogenesis. These effects may be mediated, in part, through the recovery of the BAT phenotype and brown fat cell function improvement.
format	article
author	Sara Becerril Amaia Rodríguez Victoria Catalán Neira Sáinz Beatriz Ramírez María Collantes Iván Peñuelas Javier Gómez-Ambrosi Gema Frühbeck
author_facet	Sara Becerril Amaia Rodríguez Victoria Catalán Neira Sáinz Beatriz Ramírez María Collantes Iván Peñuelas Javier Gómez-Ambrosi Gema Frühbeck
author_sort	Sara Becerril
title	Deletion of inducible nitric-oxide synthase in leptin-deficient mice improves brown adipose tissue function.
title_short	Deletion of inducible nitric-oxide synthase in leptin-deficient mice improves brown adipose tissue function.
title_full	Deletion of inducible nitric-oxide synthase in leptin-deficient mice improves brown adipose tissue function.
title_fullStr	Deletion of inducible nitric-oxide synthase in leptin-deficient mice improves brown adipose tissue function.
title_full_unstemmed	Deletion of inducible nitric-oxide synthase in leptin-deficient mice improves brown adipose tissue function.
title_sort	deletion of inducible nitric-oxide synthase in leptin-deficient mice improves brown adipose tissue function.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/d271b2f1b06c40f59d87128a4ac2c93e
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Deletion of inducible nitric-oxide synthase in leptin-deficient mice improves brown adipose tissue function.

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