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Cited by 69Mangiferin and Mango ExtractsNatural Antidiabetic Agents StudiesMetabolism, Diabetes, and Cancer

Mangiferin stimulates carbohydrate oxidation and protects against metabolic disorders induced by high-fat diets

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Apontes, Pasha, Liu, Zhongbo, Su, Kai, Benard, Outhiriaradjou, Youn, Dou Y., Li, Xisong, Li, Wei, Mirza, Raihan H. +6 more·2014·Diabetes
DOI 10.2337/db14-0006PMC PMC4207399
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Abstract

Excessive dietary fat intake causes systemic metabolic toxicity, manifested in weight gain, hyperglycemia, and insulin resistance. In addition, carbohydrate utilization as a fuel is substantially inhibited. Correction or reversal of these effects during high-fat diet (HFD) intake is of exceptional interest in light of widespread occurrence of diet-associated metabolic disorders in global human populations. Here we report that mangiferin (MGF), a natural compound (the predominant constituent of Mangifera indica extract from the plant that produces mango), protected against HFD-induced weight gain, increased aerobic mitochondrial capacity and thermogenesis, and improved glucose and insulin profiles. To obtain mechanistic insight into the basis for these effects, we determined that mice exposed to an HFD combined with MGF exhibited a substantial shift in respiratory quotient from fatty acid toward carbohydrate utilization. MGF treatment significantly increased glucose oxidation in muscle of HFD-fed mice without changing fatty acid oxidation. These results indicate that MGF redirects fuel utilization toward carbohydrates. In cultured C2C12 myotubes, MGF increased glucose and pyruvate oxidation and ATP production without affecting fatty acid oxidation, confirming in vivo and ex vivo effects. Furthermore, MGF inhibited anaerobic metabolism of pyruvate to lactate but enhanced pyruvate oxidation. A key target of MGF appears to be pyruvate dehydrogenase, determined to be activated by MGF in a variety of assays. These findings underscore the therapeutic potential of activation of carbohydrate utilization in correction of metabolic syndrome and highlight the potential of MGF to serve as a model compound that can elicit fuel-switching effects.

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  • Mangiferin administration to mice increased glucose and pyruvate oxidation and ATP production without impacting fatty acid oxidation.

    “The outcomes demonstrated heightened glucose and pyruvate oxidation and increased ATP production without impacting fatty acid oxidation.”

    From Mangifera indica L., By-Products, and Mangiferin on Cardio-Metabolic and Other Health Conditions: A Systematic Review (2023) · cites this paper as [76]

    The Results section, “MGF Promotes Carbohydrate Utilization” (page unavailable), reports increased glucose oxidation in muscle from high-fat-diet-fed mice without a significant change in palmitate oxidation. The increased pyruvate oxidation and ATP production were measured in cultured C2C12 myotubes, not demonstrated in mice; the claim extends those findings to the animals. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • For PI3K/Akt, MGF changes Akt Thr308/Ser473 and downstream GSK3β and mTORC1, leading to reduced protein synthesis and survival signaling in tumor cells, whereas in metabolic tissues, they support GLUT4 translocation and glycogen synthesis.

    “For PI3K/Akt, changes in Akt Thr308/Ser473, and downstream GSK3β and mTOR complex 1 lead to reduced protein synthesis and survival signaling in tumor cells, whereas in metabolic tissues, they support GLUT4 translocation and glycogen synthesis (16,47-54).”

    From Mangiferin in human disease: Multifaceted mechanisms and applications (Review) (2026) · cites this paper as [51]

    The Results section on carbohydrate utilization reports increased GLUT4 mRNA and glucose utilization in muscle with MGF treatment. It does not establish GLUT4 translocation or glycogen synthesis, and the passages found do not link these effects to Akt Thr308/Ser473, GSK3β, or mTORC1. They also do not address protein synthesis or survival signaling in tumor cells. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • Treatment with mangiferin in overweight patients with hyperlipidemia stimulated carbohydrate oxidation and improved glucose and insulin profiles.

    “In addition, treatment with mangiferin in overweight patients with hyperlipidemia stimulated carbohydrate oxidation and improved glucose and insulin profiles (88).”

    From Mangiferin: An effective therapeutic agent against several disorders (Review) (2018) · cites this paper as [88]

    The Abstract and Results (‘MGF Promotes Carbohydrate Utilization’) report improved glucose and insulin profiles and increased glucose oxidation with mangiferin, but these findings are from high-fat-diet-fed mice, not overweight patients with hyperlipidemia. The claim incorrectly presents the animal findings as a human treatment result. (LLM, conf=0.91)

    Experimental — accuracy not yet measured

  • Mangiferin (400 mg/kg) administered with a high fat diet to C57BL6/J mice for 16 weeks protects against HFD-induced weight gain, promotes aerobic mitochondrial capacity and increases thermogenesis.

    “Apontes et al (88) administered mangiferin (400 mg/kg) and a high fat diet (HFD) to C57BL6/J mice for 16 weeks, demonstrating that mangiferin protects against HFD-induced weight gain, promotes aerobic mitochondrial capacity and increases thermogenesis.”

    From Mangiferin: An effective therapeutic agent against several disorders (Review) (2018) · cites this paper as [88]

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Cited by

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Authors
Apontes, P., Liu, Z., Su, K., Benard, O., Youn, D. Y., Li, X., Li, W., Mirza, R. H., Bastie, C. C., Jelicks, L. A., Pessin, J. E., Muzumdar, R. H., Sauve, A. A., & Chi, Y.
Affiliations
  • Albert Einstein College of Medicine (US)
  • Weill Cornell Medicine (US)
Corresponding author
Chi, Yuling
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
2014-10-13
Volume
63
Issue
11
Pages
3626-3636
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/db14-0006
PMC
PMC4207399
OpenAlex
W2144559975
Cited by
69
References
4
Citations by year
2026: 1 · 2025: 5 · 2024: 5 · 2023: 5 · 2022: 4 · 2021: 6 · 2020: 9 · 2019: 5 · 2018: 7 · 2017: 8 · 2016: 9 · 2015: 5
FWCI
15.77
Type
journal article
Language
en
Open access
Locations
  • Diabetes (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Diabetes Association (1-11-JF-06)
  • American Heart Association (0735066N)
  • National Institutes of Health
  • School of Medicine, Indiana University
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK041296, R01DK098439, R01DK081412, P30DK072476)
Topics
  • Health Sciences › Medicine › Complementary and alternative medicine › Mangiferin and Mango Extracts
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
mangiferin, high-fat diet, carbohydrate oxidation, metabolic syndrome, insulin resistance, pyruvate oxidation, pyruvate dehydrogenase, fuel switching, respiratory quotient, mitochondrial capacity, thermogenesis, weight gain, glucose oxidation, lactic acid production, myotubes, mango
MeSH terms
Animals, Energy Metabolism, Ketone Oxidoreductases, Mice, Inbred C57BL, Oxidation-Reduction, Pyruvic Acid, Xanthones, Carbohydrate Metabolism, Lipid Metabolism, Mice, Diet, High-Fat

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