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Inhibition of hypothalamic leukemia inhibitory factor exacerbates diet-induced obesity phenotype

BACKGROUND: The consumption of large amounts of dietary fats can trigger an inflammatory response in the hypothalamus and contribute to the dysfunctional control of caloric intake and energy expenditure commonly present in obesity. The objective of this study was to identify chemokine-related transc...

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Autores principales: Fioravante, Milena, Bombassaro, Bruna, Ramalho, Albina F., Dragano, Nathalia R., Morari, Joseane, Solon, Carina, Tobar, Natalia, Ramos, Celso D., Velloso, Licio A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581454/
https://www.ncbi.nlm.nih.gov/pubmed/28865476
http://dx.doi.org/10.1186/s12974-017-0956-9
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author Fioravante, Milena
Bombassaro, Bruna
Ramalho, Albina F.
Dragano, Nathalia R.
Morari, Joseane
Solon, Carina
Tobar, Natalia
Ramos, Celso D.
Velloso, Licio A.
author_facet Fioravante, Milena
Bombassaro, Bruna
Ramalho, Albina F.
Dragano, Nathalia R.
Morari, Joseane
Solon, Carina
Tobar, Natalia
Ramos, Celso D.
Velloso, Licio A.
author_sort Fioravante, Milena
collection PubMed
description BACKGROUND: The consumption of large amounts of dietary fats can trigger an inflammatory response in the hypothalamus and contribute to the dysfunctional control of caloric intake and energy expenditure commonly present in obesity. The objective of this study was to identify chemokine-related transcripts that could be involved in the early stages of diet-induced hypothalamic inflammation. METHODS: We used immunoblot, PCR array, real-time PCR, immunofluorescence staining, glucose and insulin tolerance tests, and determination of general metabolic parameters to evaluate markers of inflammation, body mass variation, and glucose tolerance in mice fed a high-fat diet. RESULTS: Using a real-time PCR array, we identified leukemia inhibitory factor as a chemokine/cytokine undergoing a rapid increase in the hypothalamus of obesity-resistant and a rapid decrease in the hypothalamus of obesity-prone mice fed a high-fat diet for 1 day. We hypothesized that the increased hypothalamic expression of leukemia inhibitory factor could contribute to the protective phenotype of obesity-resistant mice. To test this hypothesis, we immunoneutralized hypothalamic leukemia inhibitory factor and evaluated inflammatory and metabolic parameters. The immunoneutralization of leukemia inhibitory factor in the hypothalamus of obesity-resistant mice resulted in increased body mass gain and increased adiposity. Body mass gain was mostly due to increased caloric intake and reduced spontaneous physical activity. This modification in the phenotype was accompanied by increased expression of inflammatory cytokines in the hypothalamus. In addition, the inhibition of hypothalamic leukemia inhibitory factor was accompanied by glucose intolerance and insulin resistance. CONCLUSION: Hypothalamic expression of leukemia inhibitory factor may protect mice from the development of diet-induced obesity; the inhibition of this protein in the hypothalamus transforms obesity-resistant into obesity-prone mice. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12974-017-0956-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-55814542017-09-06 Inhibition of hypothalamic leukemia inhibitory factor exacerbates diet-induced obesity phenotype Fioravante, Milena Bombassaro, Bruna Ramalho, Albina F. Dragano, Nathalia R. Morari, Joseane Solon, Carina Tobar, Natalia Ramos, Celso D. Velloso, Licio A. J Neuroinflammation Research BACKGROUND: The consumption of large amounts of dietary fats can trigger an inflammatory response in the hypothalamus and contribute to the dysfunctional control of caloric intake and energy expenditure commonly present in obesity. The objective of this study was to identify chemokine-related transcripts that could be involved in the early stages of diet-induced hypothalamic inflammation. METHODS: We used immunoblot, PCR array, real-time PCR, immunofluorescence staining, glucose and insulin tolerance tests, and determination of general metabolic parameters to evaluate markers of inflammation, body mass variation, and glucose tolerance in mice fed a high-fat diet. RESULTS: Using a real-time PCR array, we identified leukemia inhibitory factor as a chemokine/cytokine undergoing a rapid increase in the hypothalamus of obesity-resistant and a rapid decrease in the hypothalamus of obesity-prone mice fed a high-fat diet for 1 day. We hypothesized that the increased hypothalamic expression of leukemia inhibitory factor could contribute to the protective phenotype of obesity-resistant mice. To test this hypothesis, we immunoneutralized hypothalamic leukemia inhibitory factor and evaluated inflammatory and metabolic parameters. The immunoneutralization of leukemia inhibitory factor in the hypothalamus of obesity-resistant mice resulted in increased body mass gain and increased adiposity. Body mass gain was mostly due to increased caloric intake and reduced spontaneous physical activity. This modification in the phenotype was accompanied by increased expression of inflammatory cytokines in the hypothalamus. In addition, the inhibition of hypothalamic leukemia inhibitory factor was accompanied by glucose intolerance and insulin resistance. CONCLUSION: Hypothalamic expression of leukemia inhibitory factor may protect mice from the development of diet-induced obesity; the inhibition of this protein in the hypothalamus transforms obesity-resistant into obesity-prone mice. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12974-017-0956-9) contains supplementary material, which is available to authorized users. BioMed Central 2017-09-02 /pmc/articles/PMC5581454/ /pubmed/28865476 http://dx.doi.org/10.1186/s12974-017-0956-9 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Fioravante, Milena
Bombassaro, Bruna
Ramalho, Albina F.
Dragano, Nathalia R.
Morari, Joseane
Solon, Carina
Tobar, Natalia
Ramos, Celso D.
Velloso, Licio A.
Inhibition of hypothalamic leukemia inhibitory factor exacerbates diet-induced obesity phenotype
title Inhibition of hypothalamic leukemia inhibitory factor exacerbates diet-induced obesity phenotype
title_full Inhibition of hypothalamic leukemia inhibitory factor exacerbates diet-induced obesity phenotype
title_fullStr Inhibition of hypothalamic leukemia inhibitory factor exacerbates diet-induced obesity phenotype
title_full_unstemmed Inhibition of hypothalamic leukemia inhibitory factor exacerbates diet-induced obesity phenotype
title_short Inhibition of hypothalamic leukemia inhibitory factor exacerbates diet-induced obesity phenotype
title_sort inhibition of hypothalamic leukemia inhibitory factor exacerbates diet-induced obesity phenotype
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581454/
https://www.ncbi.nlm.nih.gov/pubmed/28865476
http://dx.doi.org/10.1186/s12974-017-0956-9
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