iNOS promotes hypothalamic insulin resistance associated with deregulation of energy balance and obesity in rodents

Abstract Inducible nitric oxide (iNOS)-mediated S-nitrosation of the metabolic signaling pathway has emerged as a post-translational modification that triggers insulin resistance in obesity and aging. However, the effects of S-nitrosation in controlling energy homeostasis are unknown. Thus, in the p...

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Autores principales: Carlos Kiyoshi Katashima, Vagner Ramon Rodrigues Silva, Luciene Lenhare, Rodrigo Miguel Marin, José Barreto Campello Carvalheira
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Lenguaje:EN
Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/c3aa083aeca14bd2aebfe2399c96cba1
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spelling oai:doaj.org-article:c3aa083aeca14bd2aebfe2399c96cba12021-12-02T11:52:21ZiNOS promotes hypothalamic insulin resistance associated with deregulation of energy balance and obesity in rodents10.1038/s41598-017-08920-z2045-2322https://doaj.org/article/c3aa083aeca14bd2aebfe2399c96cba12017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08920-zhttps://doaj.org/toc/2045-2322Abstract Inducible nitric oxide (iNOS)-mediated S-nitrosation of the metabolic signaling pathway has emerged as a post-translational modification that triggers insulin resistance in obesity and aging. However, the effects of S-nitrosation in controlling energy homeostasis are unknown. Thus, in the present study we aimed to evaluate the effects of S-nitrosation in insulin signaling pathway in the hypothalamus of rodents. Herein, we demonstrated that the intracerebroventricular infusion of the nitric oxide (NO) donor S-nitrosoglutathione (GSNO) promoted hypothalamic insulin signaling resistance and replicated the food intake pattern of obese individuals. Indeed, obesity induced S-nitrosation of hypothalamic IR and Akt, whereas inhibition of iNOS or S-nitrosation of insulin signaling pathway protected against hypothalamic insulin resistance and normalized energy homeostasis. Overall, these findings indicated that S-nitrosation of insulin signaling pathway is required to sustain hypothalamic insulin resistance in obesity.Carlos Kiyoshi KatashimaVagner Ramon Rodrigues SilvaLuciene LenhareRodrigo Miguel MarinJosé Barreto Campello CarvalheiraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Carlos Kiyoshi Katashima
Vagner Ramon Rodrigues Silva
Luciene Lenhare
Rodrigo Miguel Marin
José Barreto Campello Carvalheira
iNOS promotes hypothalamic insulin resistance associated with deregulation of energy balance and obesity in rodents
description Abstract Inducible nitric oxide (iNOS)-mediated S-nitrosation of the metabolic signaling pathway has emerged as a post-translational modification that triggers insulin resistance in obesity and aging. However, the effects of S-nitrosation in controlling energy homeostasis are unknown. Thus, in the present study we aimed to evaluate the effects of S-nitrosation in insulin signaling pathway in the hypothalamus of rodents. Herein, we demonstrated that the intracerebroventricular infusion of the nitric oxide (NO) donor S-nitrosoglutathione (GSNO) promoted hypothalamic insulin signaling resistance and replicated the food intake pattern of obese individuals. Indeed, obesity induced S-nitrosation of hypothalamic IR and Akt, whereas inhibition of iNOS or S-nitrosation of insulin signaling pathway protected against hypothalamic insulin resistance and normalized energy homeostasis. Overall, these findings indicated that S-nitrosation of insulin signaling pathway is required to sustain hypothalamic insulin resistance in obesity.
format article
author Carlos Kiyoshi Katashima
Vagner Ramon Rodrigues Silva
Luciene Lenhare
Rodrigo Miguel Marin
José Barreto Campello Carvalheira
author_facet Carlos Kiyoshi Katashima
Vagner Ramon Rodrigues Silva
Luciene Lenhare
Rodrigo Miguel Marin
José Barreto Campello Carvalheira
author_sort Carlos Kiyoshi Katashima
title iNOS promotes hypothalamic insulin resistance associated with deregulation of energy balance and obesity in rodents
title_short iNOS promotes hypothalamic insulin resistance associated with deregulation of energy balance and obesity in rodents
title_full iNOS promotes hypothalamic insulin resistance associated with deregulation of energy balance and obesity in rodents
title_fullStr iNOS promotes hypothalamic insulin resistance associated with deregulation of energy balance and obesity in rodents
title_full_unstemmed iNOS promotes hypothalamic insulin resistance associated with deregulation of energy balance and obesity in rodents
title_sort inos promotes hypothalamic insulin resistance associated with deregulation of energy balance and obesity in rodents
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/c3aa083aeca14bd2aebfe2399c96cba1
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AT lucienelenhare inospromoteshypothalamicinsulinresistanceassociatedwithderegulationofenergybalanceandobesityinrodents
AT rodrigomiguelmarin inospromoteshypothalamicinsulinresistanceassociatedwithderegulationofenergybalanceandobesityinrodents
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