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Cited by 64Mangiferin and Mango ExtractsNatural Antidiabetic Agents StudiesMetabolism, Diabetes, and Cancer

Dual mode action of mangiferin in mouse liver under high fat diet

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Lim, Jihyeon, Liu, Zhongbo, Apontes, Pasha, Feng, Daorong, Pessin, Jeffrey E., Sauve, Anthony A., Angeletti, Ruth H., Chi, Yuling·2014·PLoS ONE
DOI 10.1371/journal.pone.0090137PMC PMC3943915
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Abstract

Chronic over-nutrition is a major contributor to the spread of obesity and its related metabolic disorders. Development of therapeutics has been slow compared to the speedy increase in occurrence of these metabolic disorders. We have identified a natural compound, mangiferin (MGF) (a predominant component of the plants of Anemarrhena asphodeloides and Mangifera indica), that can protect against high fat diet (HFD) induced obesity, hyperglycemia, insulin resistance and hyperlipidemia in mice. However, the molecular mechanisms whereby MGF exerts these beneficial effects are unknown. To understand MGF mechanisms of action, we performed unbiased quantitative proteomic analysis of protein profiles in liver of mice fed with HFD utilizing 15N metabolically labeled liver proteins as internal standards. We found that out of 865 quantified proteins 87 of them were significantly differentially regulated by MGF. Among those 87 proteins, 50% of them are involved in two major processes, energy metabolism and biosynthesis of metabolites. Further classification indicated that MGF increased proteins important for mitochondrial biogenesis and oxidative activity including oxoglutarate dehydrogenase E1 (Dhtkd1) and cytochrome c oxidase subunit 6B1 (Cox6b1). Conversely, MGF reduced proteins critical for lipogenesis such as fatty acid stearoyl-CoA desaturase 1 (Scd1) and acetyl-CoA carboxylase 1 (Acac1). These mass spectrometry data were confirmed and validated by western blot assays. Together, data indicate that MGF upregulates proteins pivotal for mitochondrial bioenergetics and downregulates proteins controlling de novo lipogenesis. This novel mode of dual pharmacodynamic actions enables MGF to enhance energy expenditure and inhibit lipogenesis, and thereby correct HFD induced liver steatosis and prevent adiposity. This provides a molecular basis supporting development of MGF or its metabolites into therapeutics to treat metabolic disorders.

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  • Out of 865 quantified proteins, 87 are differentially regulated by mangiferin in C57BL6/J mice fed mixed granules containing mangiferin and HFD for 18 weeks.

    “It was demonstrated that out of 865 quantified proteins, 87 of them are differentially regulated by mangiferin.”

    From Mangiferin: An effective therapeutic agent against several disorders (Review) (2018) · cites this paper as [89]

  • Mangiferin decreases expression of proteins critical for lipogenesis, including fatty acid stearoyl-CoA desaturase 1 and acetyl-CoA carboxylase 1.

    “In addition, mangiferin decreases the expression of proteins that are critical for lipogenesis, including fatty acid stearoyl-CoA desaturase 1 and acetyl-CoA carboxylase 1 (89).”

    From Mangiferin: An effective therapeutic agent against several disorders (Review) (2018) · cites this paper as [89]

  • Of these proteins, approximately 50% are involved in energy metabolism and metabolite biosynthesis.

    “Of these proteins, ~50% are involved in energy metabolism and metabolite biosynthesis.”

    From Mangiferin: An effective therapeutic agent against several disorders (Review) (2018) · cites this paper as [89]

  • Mangiferin increases expression of proteins crucial for mitochondrial biogenesis and oxidative activity, including oxoglutarate dehydrogenase E1 and cytochrome c oxidase subunit 6B1.

    “Further classification indicated that mangiferin increases the expression of proteins that are crucial for mitochondrial biogenesis and oxidative activity, including oxoglutarate dehydrogenase E1 and cytochrome c oxidase subunit 6B1.”

    From Mangiferin: An effective therapeutic agent against several disorders (Review) (2018) · cites this paper as [89]

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Authors
Lim, J., Liu, Z., Apontes, P., Feng, D., Pessin, J. E., Sauve, A. A., Angeletti, R. H., & Chi, Y.
Affiliations
  • Albert Einstein College of Medicine (US)
  • Weill Cornell Medicine (US)
Corresponding author
  • Lim, Jihyeon
  • Liu, Zhongbo
  • Chi, Yuling
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2014-03-05
Volume
9
Issue
3
Pages
e90137
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0090137
PMC
PMC3943915
OpenAlex
W2011857209
Cited by
64
References
5
Citations by year
2025: 1 · 2024: 7 · 2023: 6 · 2022: 3 · 2021: 4 · 2020: 8 · 2019: 3 · 2018: 7 · 2017: 10 · 2016: 8 · 2015: 4 · 2014: 3
FWCI
17.92
Type
journal article
Language
en
Update notices
correction (2014-06-17)
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • American Diabetes Association (1-11-JF-06)
  • American Heart Association (0735066N)
  • National Institutes of Health (DK41296, RO1-DK-49688)
  • National Institute of General Medical Sciences (R01GM106072)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK041296, R01-DK49688, R01DK049688, DK-49688, R01DK098439, DK41296, P60DK020541)
  • National Center for Research Resources (S10RR021056, S10RR015859)
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, obesity, hepatic steatosis, mitochondrial biogenesis, de novo lipogenesis, energy metabolism, quantitative proteomics, insulin resistance, hyperlipidemia, 2-oxoglutarate dehydrogenase, cytochrome c oxidase, stearoyl-CoA desaturase 1, acetyl-CoA carboxylase 1, Anemarrhena asphodeloides, mango, natural compounds
MeSH terms
Animals, Cells, Cultured, Energy Metabolism, Lipids, Liver, Mice, Inbred C57BL, Mitochondria, Obesity, Organ Size, Anti-Obesity Agents, Proteome, Xanthones, Lipid Metabolism, Metabolic Networks and Pathways, Diet, High-Fat

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