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

Jihyeon Lim, Zhongbo Liu, Pasha Apontes, Daorong Feng, Jeffrey E. Pessin, Anthony A. Sauve, Ruth H. Angeletti, Yuling Chi

Research output: Contribution to journalArticle

35 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere90137
JournalPLoS One
Volume9
Issue number3
DOIs
StatePublished - Mar 5 2014

Fingerprint

High Fat Diet
high fat diet
Nutrition
Liver
mechanism of action
Fats
liver
mice
lipogenesis
metabolic diseases
Lipogenesis
proteins
Proteins
Energy Metabolism
energy metabolism
obesity
Metabolites
metabolites
Anemarrhena
process energy

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Dual mode action of mangiferin in mouse liver under high fat diet. / Lim, Jihyeon; Liu, Zhongbo; Apontes, Pasha; Feng, Daorong; Pessin, Jeffrey E.; Sauve, Anthony A.; Angeletti, Ruth H.; Chi, Yuling.

In: PLoS One, Vol. 9, No. 3, e90137, 05.03.2014.

Research output: Contribution to journalArticle

Lim, J, Liu, Z, Apontes, P, Feng, D, Pessin, JE, Sauve, AA, Angeletti, RH & Chi, Y 2014, 'Dual mode action of mangiferin in mouse liver under high fat diet', PLoS One, vol. 9, no. 3, e90137. https://doi.org/10.1371/journal.pone.0090137
Lim, Jihyeon ; Liu, Zhongbo ; Apontes, Pasha ; Feng, Daorong ; Pessin, Jeffrey E. ; Sauve, Anthony A. ; Angeletti, Ruth H. ; Chi, Yuling. / Dual mode action of mangiferin in mouse liver under high fat diet. In: PLoS One. 2014 ; Vol. 9, No. 3.
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