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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Nature Portfolio
2017
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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) |
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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 |
work_keys_str_mv |
AT carloskiyoshikatashima inospromoteshypothalamicinsulinresistanceassociatedwithderegulationofenergybalanceandobesityinrodents AT vagnerramonrodriguessilva inospromoteshypothalamicinsulinresistanceassociatedwithderegulationofenergybalanceandobesityinrodents AT lucienelenhare inospromoteshypothalamicinsulinresistanceassociatedwithderegulationofenergybalanceandobesityinrodents AT rodrigomiguelmarin inospromoteshypothalamicinsulinresistanceassociatedwithderegulationofenergybalanceandobesityinrodents AT josebarretocampellocarvalheira inospromoteshypothalamicinsulinresistanceassociatedwithderegulationofenergybalanceandobesityinrodents |
_version_ |
1718395068316909568 |