Dual effects of sodium tungstate on adipocyte biology: inhibition of adipogenesis and stimulation of cellular oxygen consumption

Carmona, Mamen; Amigó, Montserrat; Barceló-Batllori, Sílvia; Julià, Marta; Esteban, Yaiza; Moreno, Sílvia; Gomis, Ramón

doi:10.1038/ijo.2009.34

Cited by 9 publications

(14 citation statements)

References 43 publications

(47 reference statements)

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“…The function of the neurofilament family of proteins is regulated by MAPK and STAT3. We have demonstrated that sodium tungstate regulates both factors in the hypothalamus, as shown by our icv studies, and in other tissues [28], [34]. GFAP, a characterized marker of intermediate filaments in glial cells, is also regulated by sodium tungstate, as seen in proteomic and immunohistochemistry studies.…”

Section: Discussionsupporting

confidence: 59%

Anti-Obesity Sodium Tungstate Treatment Triggers Axonal and Glial Plasticity in Hypothalamic Feeding Centers

et al. 2012

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ObjectiveThis 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.MethodsAdult 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.ResultsSodium 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.ConclusionsAltogether, 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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Section: Discussionsupporting

confidence: 59%

Anti-Obesity Sodium Tungstate Treatment Triggers Axonal and Glial Plasticity in Hypothalamic Feeding Centers

et al. 2012

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“…During adipogenesis, expression of LIP decreases (Tang et al, 2003), whereas inhibition of adipocyte differentiation results in increased expression of LIP (Carmona et al, 2009;Zhou et al, 2010). Moreover, LIP acts as a dominant-negative inhibitor of the pro-adipogenic LAP isoform of C/EBPβ (Yeh et al, 1995b;Hamm et al, 2001;Bae and Kim, 2005) and interferes with terminal adipocyte differentiation (Calkhoven et al, 2000).…”

Section: C/ebpβ In Adipocytesmentioning

confidence: 99%

Instruction of mesenchymal cell fate by the transcription factor C/EBPβ

Smink¹,

Leutz²

2012

Gene

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“…Tissues were homogenized and centrifuged, and supernatants were collected. Protein isolation from cell culture was performed as previously described [21]. Proteins were quantified and subjected to western blot separation in an 8% acrylamide gel and transferred to polyvinylidene fluoride (PVDF) membranes.…”

Section: Protein Extraction and Western Blotmentioning

confidence: 99%

“…Sodium tungstate is a new and promising compound with anti-obesity and antidiabetic effects [19,20]. Sodium tungstate blocks adipocyte differentiation and increases mitochondrial oxygen consumption in vitro [21]. In vivo, sodium tungstate enhances thermogenesis in brown adipose tissue and lipid oxidation in white adipose tissue of diet-induced obese animals [19,22,23].…”

Section: Introductionmentioning

confidence: 99%

Sodium tungstate regulates food intake and body weight through activation of the hypothalamic leptin pathway

Amigó-Correig

Barceló-Batllori

Piquer

et al. 2011

Diabetes, Obesity and Metabolism

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Aims: Sodium tungstate is an anti‐obesity drug targeting peripheral tissues. In vivo, sodium tungstate reduces body weight gain and food intake through increasing energy expenditure and lipid oxidation, but it also modulates hypothalamic gene expression when orally administered, raising the possibility of a direct effect of sodium tungstate on the central nervous system. Methods: Sodium tungstate was administered intraperitoneally (ip) to Wistar rats, and its levels were measured in cerebrospinal fluid through mass spectrometry. Body weight gain and food intake were monitored for 24 h after its administration in the third ventricle. Hypothalamic protein was obtained and subjected to western blot. In vitro, hypothalamic N29/4 cells were treated with 100 µM sodium tungstate or 1 nM leptin, and protein and neural gene expression were analysed. Results: Sodium tungstate crossed the blood–brain barrier, reaching a concentration of 1.31 ± 0.07 mg/l in cerebrospinal fluid 30 min after ip injection. When centrally administered, sodium tungstate decreased body weight gain and food intake and increased the phosphorylation state of the main kinases and proteins involved in leptin signalling. In vitro, sodium tungstate increased the phosphorylation of janus kinase‐2 (JAK2) and extracellular signal‐regulated kinase‐1/2 (ERK1/2), but the activation of each kinase did not depend on each other. It regulated c‐myc gene expression through the JAK2/STAT system and c‐fos and AgRP (agouti‐related peptide) gene expression through the ERK1/2 pathway simultaneously and independently. Conclusions: Sodium tungstate increased the activity of several kinases involved in the leptin signalling system in an independent way, making it a suitable and promising candidate as a leptin‐mimetic compound in order to manage obesity.

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Dual effects of sodium tungstate on adipocyte biology: inhibition of adipogenesis and stimulation of cellular oxygen consumption

Cited by 9 publications

References 43 publications

Anti-Obesity Sodium Tungstate Treatment Triggers Axonal and Glial Plasticity in Hypothalamic Feeding Centers

Anti-Obesity Sodium Tungstate Treatment Triggers Axonal and Glial Plasticity in Hypothalamic Feeding Centers

Instruction of mesenchymal cell fate by the transcription factor C/EBPβ

Sodium tungstate regulates food intake and body weight through activation of the hypothalamic leptin pathway

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