Anti-obesity sodium tungstate treatment triggers axonal and glial plasticity in hypothalamic feeding centers

This study aims at exploring the effects of sodium tungstate treatment on hypothalamic plasticity, which is known to have an important role in the control of energy metabolism. Adult lean and high-fat diet-induced obese mice were orally treated with sodium tungstate. Arcuate and paraventricular nucl...

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Veröffentlicht in:PloS one 2012-07, Vol.7 (7), p.e39087-e39087
Hauptverfasser: Amigó-Correig, Marta, Barceló-Batllori, Sílvia, Soria, Guadalupe, Krezymon, Alice, Benani, Alexandre, Pénicaud, Luc, Tudela, Raúl, Planas, Anna Maria, Fernández, Eduardo, Carmona, Maria del Carmen, Gomis, Ramon
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creator Amigó-Correig, Marta
Barceló-Batllori, Sílvia
Soria, Guadalupe
Krezymon, Alice
Benani, Alexandre
Pénicaud, Luc
Tudela, Raúl
Planas, Anna Maria
Fernández, Eduardo
Carmona, Maria del Carmen
Gomis, Ramon
description This study aims at exploring the effects of sodium tungstate treatment on hypothalamic plasticity, which is known to have an important role in the control of energy metabolism. Adult lean and high-fat diet-induced obese mice were orally treated with sodium tungstate. Arcuate and paraventricular nuclei and lateral hypothalamus were separated and subjected to proteomic analysis by DIGE and mass spectrometry. Immunohistochemistry and in vivo magnetic resonance imaging were also performed. Sodium tungstate treatment reduced body weight gain, food intake, and blood glucose and triglyceride levels. These effects were associated with transcriptional and functional changes in the hypothalamus. Proteomic analysis revealed that sodium tungstate modified the expression levels of proteins involved in cell morphology, axonal growth, and tissue remodeling, such as actin, CRMP2 and neurofilaments, and of proteins related to energy metabolism. Moreover, immunohistochemistry studies confirmed results for some targets and further revealed tungstate-dependent regulation of SNAP25 and HPC-1 proteins, suggesting an effect on synaptogenesis as well. Functional test for cell activity based on c-fos-positive cell counting also suggested that sodium tungstate modified hypothalamic basal activity. Finally, in vivo magnetic resonance imaging showed that tungstate treatment can affect neuronal organization in the hypothalamus. Altogether, these results suggest that sodium tungstate regulates proteins involved in axonal and glial plasticity. The fact that sodium tungstate could modulate hypothalamic plasticity and networks in adulthood makes it a possible and interesting therapeutic strategy not only for obesity management, but also for other neurodegenerative illnesses like Alzheimer's disease.
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Adult lean and high-fat diet-induced obese mice were orally treated with sodium tungstate. Arcuate and paraventricular nuclei and lateral hypothalamus were separated and subjected to proteomic analysis by DIGE and mass spectrometry. Immunohistochemistry and in vivo magnetic resonance imaging were also performed. Sodium tungstate treatment reduced body weight gain, food intake, and blood glucose and triglyceride levels. These effects were associated with transcriptional and functional changes in the hypothalamus. Proteomic analysis revealed that sodium tungstate modified the expression levels of proteins involved in cell morphology, axonal growth, and tissue remodeling, such as actin, CRMP2 and neurofilaments, and of proteins related to energy metabolism. Moreover, immunohistochemistry studies confirmed results for some targets and further revealed tungstate-dependent regulation of SNAP25 and HPC-1 proteins, suggesting an effect on synaptogenesis as well. Functional test for cell activity based on c-fos-positive cell counting also suggested that sodium tungstate modified hypothalamic basal activity. Finally, in vivo magnetic resonance imaging showed that tungstate treatment can affect neuronal organization in the hypothalamus. Altogether, these results suggest that sodium tungstate regulates proteins involved in axonal and glial plasticity. 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This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Adult lean and high-fat diet-induced obese mice were orally treated with sodium tungstate. Arcuate and paraventricular nuclei and lateral hypothalamus were separated and subjected to proteomic analysis by DIGE and mass spectrometry. Immunohistochemistry and in vivo magnetic resonance imaging were also performed. Sodium tungstate treatment reduced body weight gain, food intake, and blood glucose and triglyceride levels. These effects were associated with transcriptional and functional changes in the hypothalamus. Proteomic analysis revealed that sodium tungstate modified the expression levels of proteins involved in cell morphology, axonal growth, and tissue remodeling, such as actin, CRMP2 and neurofilaments, and of proteins related to energy metabolism. Moreover, immunohistochemistry studies confirmed results for some targets and further revealed tungstate-dependent regulation of SNAP25 and HPC-1 proteins, suggesting an effect on synaptogenesis as well. Functional test for cell activity based on c-fos-positive cell counting also suggested that sodium tungstate modified hypothalamic basal activity. Finally, in vivo magnetic resonance imaging showed that tungstate treatment can affect neuronal organization in the hypothalamus. Altogether, these results suggest that sodium tungstate regulates proteins involved in axonal and glial plasticity. The fact that sodium tungstate could modulate hypothalamic plasticity and networks in adulthood makes it a possible and interesting therapeutic strategy not only for obesity management, but also for other neurodegenerative illnesses like Alzheimer's disease.</description><subject>Actin</subject><subject>Alzheimer's disease</subject><subject>Animals</subject><subject>Axonal plasticity</subject><subject>Axons - drug effects</subject><subject>Biology</subject><subject>Blood glucose</subject><subject>Body weight</subject><subject>Body weight gain</subject><subject>Brain</subject><subject>c-Fos protein</subject><subject>Cell morphology</subject><subject>Compostos de tungstè</subject><subject>Control methods</subject><subject>Cytology</subject><subject>Diabetes</subject><subject>Diabetis</subject><subject>Diet, High-Fat</subject><subject>Disease control</subject><subject>Drug therapy</subject><subject>Energy metabolism</subject><subject>Energy Metabolism - drug effects</subject><subject>Expressió gènica</subject><subject>Food and Nutrition</subject><subject>Food intake</subject><subject>Gene expression</subject><subject>Glial plasticity</subject><subject>High fat diet</subject><subject>Hypothalamus</subject><subject>Hypothalamus (lateral)</subject><subject>Hypothalamus - 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drug effects</topic><topic>Biology</topic><topic>Blood glucose</topic><topic>Body weight</topic><topic>Body weight gain</topic><topic>Brain</topic><topic>c-Fos protein</topic><topic>Cell morphology</topic><topic>Compostos de tungstè</topic><topic>Control methods</topic><topic>Cytology</topic><topic>Diabetes</topic><topic>Diabetis</topic><topic>Diet, High-Fat</topic><topic>Disease control</topic><topic>Drug therapy</topic><topic>Energy metabolism</topic><topic>Energy Metabolism - drug effects</topic><topic>Expressió gènica</topic><topic>Food and Nutrition</topic><topic>Food intake</topic><topic>Gene expression</topic><topic>Glial plasticity</topic><topic>High fat diet</topic><topic>Hypothalamus</topic><topic>Hypothalamus (lateral)</topic><topic>Hypothalamus - drug effects</topic><topic>Hypothalamus - physiology</topic><topic>Illnesses</topic><topic>Immunohistochemistry</topic><topic>In vivo methods and tests</topic><topic>Intercellular Signaling Peptides and Proteins</topic><topic>Kinases</topic><topic>Life Sciences</topic><topic>Magnetic resonance</topic><topic>Magnetic resonance imaging</topic><topic>Malaltia d'Alzheimer</topic><topic>Male</topic><topic>Mass spectrometry</topic><topic>Mass spectroscopy</topic><topic>Medicine</topic><topic>Metabolism</topic><topic>Metabolisme</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Obese</topic><topic>Muscle proteins</topic><topic>Nerve Tissue Proteins - 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Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Recercat</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Amigó-Correig, Marta</au><au>Barceló-Batllori, Sílvia</au><au>Soria, Guadalupe</au><au>Krezymon, Alice</au><au>Benani, Alexandre</au><au>Pénicaud, Luc</au><au>Tudela, Raúl</au><au>Planas, Anna Maria</au><au>Fernández, Eduardo</au><au>Carmona, Maria del Carmen</au><au>Gomis, Ramon</au><au>Alquier, Thierry</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anti-obesity sodium tungstate treatment triggers axonal and glial plasticity in hypothalamic feeding centers</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-07-03</date><risdate>2012</risdate><volume>7</volume><issue>7</issue><spage>e39087</spage><epage>e39087</epage><pages>e39087-e39087</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>This study aims at exploring the effects of sodium tungstate treatment on hypothalamic plasticity, which is known to have an important role in the control of energy metabolism. Adult lean and high-fat diet-induced obese mice were orally treated with sodium tungstate. Arcuate and paraventricular nuclei and lateral hypothalamus were separated and subjected to proteomic analysis by DIGE and mass spectrometry. Immunohistochemistry and in vivo magnetic resonance imaging were also performed. Sodium tungstate treatment reduced body weight gain, food intake, and blood glucose and triglyceride levels. These effects were associated with transcriptional and functional changes in the hypothalamus. Proteomic analysis revealed that sodium tungstate modified the expression levels of proteins involved in cell morphology, axonal growth, and tissue remodeling, such as actin, CRMP2 and neurofilaments, and of proteins related to energy metabolism. Moreover, immunohistochemistry studies confirmed results for some targets and further revealed tungstate-dependent regulation of SNAP25 and HPC-1 proteins, suggesting an effect on synaptogenesis as well. Functional test for cell activity based on c-fos-positive cell counting also suggested that sodium tungstate modified hypothalamic basal activity. Finally, in vivo magnetic resonance imaging showed that tungstate treatment can affect neuronal organization in the hypothalamus. Altogether, these results suggest that sodium tungstate regulates proteins involved in axonal and glial plasticity. The fact that sodium tungstate could modulate hypothalamic plasticity and networks in adulthood makes it a possible and interesting therapeutic strategy not only for obesity management, but also for other neurodegenerative illnesses like Alzheimer's disease.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22802935</pmid><doi>10.1371/journal.pone.0039087</doi><tpages>e39087</tpages><orcidid>https://orcid.org/0000-0003-2046-0162</orcidid><orcidid>https://orcid.org/0000-0001-7420-651X</orcidid><orcidid>https://orcid.org/0000-0002-8344-0479</orcidid><oa>free_for_read</oa></addata></record>
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subjects Actin
Alzheimer's disease
Animals
Axonal plasticity
Axons - drug effects
Biology
Blood glucose
Body weight
Body weight gain
Brain
c-Fos protein
Cell morphology
Compostos de tungstè
Control methods
Cytology
Diabetes
Diabetis
Diet, High-Fat
Disease control
Drug therapy
Energy metabolism
Energy Metabolism - drug effects
Expressió gènica
Food and Nutrition
Food intake
Gene expression
Glial plasticity
High fat diet
Hypothalamus
Hypothalamus (lateral)
Hypothalamus - drug effects
Hypothalamus - physiology
Illnesses
Immunohistochemistry
In vivo methods and tests
Intercellular Signaling Peptides and Proteins
Kinases
Life Sciences
Magnetic resonance
Magnetic resonance imaging
Malaltia d'Alzheimer
Male
Mass spectrometry
Mass spectroscopy
Medicine
Metabolism
Metabolisme
Mice
Mice, Inbred C57BL
Mice, Obese
Muscle proteins
Nerve Tissue Proteins - drug effects
Neurofilaments
Neuroglia - drug effects
Neuronal Plasticity - drug effects
Neurosciences
NMR
Nuclear magnetic resonance
Nutrition
Obesitat
Obesity
Obesity - drug therapy
Paraventricular nucleus
Physiological aspects
Plastic properties
Plasticity
Protein Processing, Post-Translational
Proteins
Proteomics
Rates (Animals de laboratori)
Rats as laboratory animals
Resonance
Ressonància magnètica
Rodents
SNAP-25 protein
Sodium
Sodium tungstate
Synaptogenesis
Transcription
Triglycerides
Tungsten compounds
Tungsten Compounds - therapeutic use
Weight reduction
title Anti-obesity sodium tungstate treatment triggers axonal and glial plasticity in hypothalamic feeding centers
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