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Int. J. Mol. Sci. 2018, 19(1), 201; doi:10.3390/ijms19010201

Mangiferin Accelerates Glycolysis and Enhances Mitochondrial Bioenergetics

Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Einstein Stable Isotope and Metabolomics Core, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Author to whom correspondence should be addressed.
Received: 1 December 2017 / Revised: 23 December 2017 / Accepted: 27 December 2017 / Published: 9 January 2018
(This article belongs to the Special Issue Natural and Semi-Synthetic Small Molecules in Drug Discovery)
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One of the main causes of hyperglycemia is inefficient or impaired glucose utilization by skeletal muscle, which can be exacerbated by chronic high caloric intake. Previously, we identified a natural compound, mangiferin (MGF) that improved glucose utilization in high fat diet (HFD)-induced insulin resistant mice. To further identify the molecular mechanisms of MGF action on glucose metabolism, we conducted targeted metabolomics and transcriptomics studies of glycolyic and mitochondrial bioenergetics pathways in skeletal muscle. These data revealed that MGF increased glycolytic metabolites that were further augmented as glycolysis proceeded from the early to the late steps. Consistent with an MGF-stimulation of glycolytic flux there was a concomitant increase in the expression of enzymes catalyzing glycolysis. MGF also increased important metabolites in the tricarboxylic acid (TCA) cycle, such as α-ketoglutarate and fumarate. Interestingly however, there was a reduction in succinate, a metabolite that also feeds into the electron transport chain to produce energy. MGF increased succinate clearance by enhancing the expression and activity of succinate dehydrogenase, leading to increased ATP production. At the transcriptional level, MGF induced mRNAs of mitochondrial genes and their transcriptional factors. Together, these data suggest that MGF upregulates mitochondrial oxidative capacity that likely drives the acceleration of glycolysis flux. View Full-Text
Keywords: mangiferin; glucose; glycolysis; TCA cycle; mitochondrial bioenergetics; metabolomics; transcriptomics mangiferin; glucose; glycolysis; TCA cycle; mitochondrial bioenergetics; metabolomics; transcriptomics

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Liu, Z.; Apontes, P.; Fomenko, E.V.; Chi, N.; Schuster, V.L.; Kurland, I.J.; Pessin, J.E.; Chi, Y. Mangiferin Accelerates Glycolysis and Enhances Mitochondrial Bioenergetics. Int. J. Mol. Sci. 2018, 19, 201.

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