Anti-obesity sodium tungstate treatment triggers axonal and glial plasticity in hypothalamic feeding centers.
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.
Diabetes and Obesity Laboratory, Institut d'investigacions Biomèdiques August Pi i Sunyer, Endocrinology and Nutrition Unit-Hospital Clínic, Barcelona, Spain.
Marta
M
Amigó-Correig
Sílvia
S
Barceló-Batllori
Guadalupe
G
Soria
Alice
A
Krezymon
Alexandre
A
Benani
Luc
L
Pénicaud
Raúl
R
Tudela
Anna Maria
AM
Planas
Eduardo
E
Fernández
Maria del Carmen
Mdel C
Carmona
Ramon
R
Gomis
D000818:Animals; D001369:Axons / Q000187:drug effects*; D059305:Diet, High-Fat; D004734:Energy Metabolism / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009419:Nerve Tissue Proteins / Q000187:drug effects; D009457:Neuroglia / Q000187:drug effects*; D009473:Neuronal Plasticity / Q000187:drug effects*; D009765:Obesity / Q000188:drug therapy*; D011499:Protein Processing, Post-Translational; D017973:Tungsten Compounds / Q000627:therapeutic use*
D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D017973:Tungsten Compounds; C095114:collapsin response mediator protein-2; C025399:sodium tungstate(VI)