Metabolic Variations between Low-Grade and High-Grade Gliomas-Profiling by 1H NMR Spectroscopy.

Altered cellular metabolism is one of the crucial hallmarks of glioma that deserves exploration, as the metabolites act as direct indicators of protein function and genetic variations. The current study focused on the metabolomic profiling of patients from whom glioma specimens were obtained for the identification of specific metabolites that could distinguish the low grade and high grade. In the current study, 1H NMR spectroscopy was carried out and the data were analyzed by partial least-squares discriminant analysis (PLS-DA) and orthogonal projection to latent structure with discriminant analysis (OPLS-DA). Pathway analysis was done to associate characteristic metabolites with the grades of sample using MetaboAnalyst 4.0 software based on the KEGG metabolic pathways database. Distinctive metabolic profiles among low- and high-grade gliomas with top 15 characteristic metabolites that could discriminate these grades were identified on the basis of their VIP scores from the OPLS-DA model. The major altered metabolic pathways include choline, taurine and hypotaurine, glutamate/glutamine, glutathione, and phenyl alanine/tyrosine, which were found to be consistent with the particular grade of a sample. Our study clearly demonstrated a characteristic metabolic profile of individual grades of glioma, suggesting that an altered metabolism is consistent with the specific grades of glioma appreciation and could lead to the development novel treatment strategies.

Connexin 30 mediated rewiring of glucose metabolism in rat C6 xenograft and grades of glioma.

Connexin 30 (Cx30), a tumour-suppressive gap junctional protein, impacts on insulin-like growth factor receptor 1-mediated progression and stemness of glioma. Of late, metabolic reprogramming, a recently adjudged hall mark of malignancy, could reasonably associated with the changes in gap junctional communication in glioma. This newly recognized hallmark of reprogramming of metabolism to maintain the rapid proliferation necessitates further probing to establish the stronger hall marks. Hence, the current study attempted to link the association between the expression of Cx30 with glucose uptake and glucose metabolism in glioma. We have transfected Cx30 in C6 glioma cells, characterized by a low level of intercellular communication and developed xenografts to study the status of glucose transporters (GLUTs), hexokinase 2 and Pyruvate dehydrogenase kinase 1 (PDK 1) along with human glioma tissues by RT-PCR and immunoblotting. The results showed a significant increase in the levels of GLUTs, hexokinase 2 and PDK 1 in C6-implanted rat xenografts and high grades compared to their respective controls, whereas Cx30-transfected C6-implanted rat xenograft and low grades show no significant change compared to that of controls supporting the association between Gap junctional communications and glucose metabolism. We strongly speculate the impact of Cx30 over the glucose metabolism that might provide therapeutic prospects and challenges for anti-glycolytic cancer therapy.