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

Abstract

OBJECTIVE:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Marta Amigó-Correig, Sílvia Barceló-Batllori, Guadalupe Soria, Alice Krezymon, Alexandre Benani, Luc Pénicaud, Raúl Tudela, Anna Maria Planas, Eduardo Fernández, Maria del Carmen Carmona, Ramon Gomis
• Journal: PloS one (PLoS One) Vol. 7 Issue 7 Pg. e39087 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 22802935 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Intercellular Signaling Peptides and Proteins
• Nerve Tissue Proteins
• Tungsten Compounds
• collapsin response mediator protein-2
• sodium tungstate(VI)

Topics

• Animals
• Axons (drug effects)
• Diet, High-Fat
• Energy Metabolism (drug effects)
• Hypothalamus (drug effects, physiology)
• Intercellular Signaling Peptides and Proteins
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Obese
• Nerve Tissue Proteins (drug effects)
• Neuroglia (drug effects)
• Neuronal Plasticity (drug effects)
• Obesity (drug therapy)
• Protein Processing, Post-Translational
• Tungsten Compounds (therapeutic use)