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Metabolic Pathway Analysis of Biochanin A Administration On Obesity‐Induced Metabolic Dysfunction
Author(s) -
Hong MoonJu,
Park HeeSook,
Kim SoonHee,
Jeong NamJoo,
Kim MyungSunny
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.655.7
Subject(s) - biochanin a , lipid metabolism , metabolomics , endocrinology , metabolic pathway , medicine , metabolism , steatosis , insulin resistance , chemistry , pyrimidine metabolism , metabolome , isoflavones , biology , biochemistry , metabolite , obesity , purine , daidzein , genistein , enzyme , chromatography
Metabolomics is a powerful technology used in biomarker discovery and assessing the physiological effects in neutraceuticals and pharmaceuticals. Modulation of the metabolic responses associated with obesity may help prevent or improve obesity‐induced metabolic dysfunctions. Recently, we reported that biochanin A (BA), dietary bioactive isoflavone that is most commonly found in red clover, peanuts, alfalfa sprouts and soy ameliorates impaired lipid homeostasis in obesity‐induced hepatic steatosis. In this study, capillary electrophoresis‐MS (CE‐MS)‐based metabolic was used to elucidate the physiological function of biochanin A in obesity‐induced insulin resistance and hepatic steatosis. C57BL/6 mice were fed a normal chow diet (NC), a high‐fat diet (HFD), and a HFD supplemented with 0.05% BA for 12 weeks. The metabolites analysis of frozen liver tissues homogenized and centrifuged and then subjected metabolomics analysis using CE‐MS. Identified 257 possible metabolites and 110 metabolites were quantified. A Partial least squares discriminant analysis (PLS‐DA) scores plot showed that cluster of BA treatment group shift the HFD group toward the NC group. A loading plot was generated to detect the metabolites responsible for the differentiation in the score plots. In the metabolic pathway analysis of significantly altered metabolites, it showed that the changed metabolites were responsible for glutathione metabolism, glycine, serine and threonine metabolism, arginine and proline metabolism, purine metabolism (−log(p) > 4.5 or pathway impact (pathway impact > 0.1) between the NC and HFD group. Among these metabolites, the increased metabolites involved in glutathione metabolism and decreased purine metabolism in obese mice were reversed by BA administration with HFD. BA administration also promoted the recovery of metabolites involved in fatty acid oxidation, synthesis of phosphatidylcholine, triglycerol metabolism, and glucose metabolism in the livers of obese mice. The glutathione and purine metabolism showed positive correlations with insulin resistance and inflammatory makers of serum, such as abnormal blood glucose, insulin levels, homeostasis model assessment insulin resistance index (HOMA‐IR), monocyte chemoattractant protein (MCP)‐1, plasminogen activator inhibitor (PAI)‐1 in diet‐induced obese mice. Taken together, these results showed that BA ameliorates metabolic dysfunction such as insulin resistance and inflammation by regulating glutathione and purine metabolism. Thus, BA may be a potential therapeutic agent for the prevention of obesity‐mediated metabolic dysfunction. Moreover, metabolomics approach of pharmaceuticals can explain the molecular insight in nutritional research. Support or Funding Information This study was supported by the grant of Korea Food Research Institute