Multiplatform Metabolomics Investigation of Antiadipogenic Effects on 3T3-L1 Adipocytes by a Potent Diarylheptanoid

Dan Du, Haiwei Gu, Danijel Djukovic, Lisa Bettcher, Meng Gong, Wen Zheng, Liqiang Hu, Xinyu Zhang, Renke Zhang, Dongfang Wang, Daniel Raftery

    Research output: Contribution to journalArticle

    3 Citations (Scopus)

    Abstract

    Obesity is fast becoming a serious health problem worldwide. Of the many possible antiobesity strategies, one interesting approach focuses on blocking adipocyte differentiation and lipid accumulation to counteract the rise in fat storage. However, there is currently no drug available for the treatment of obesity that works by inhibiting adipocyte differentiation. Here we use a broad-based metabolomics approach to interrogate and better understand metabolic changes that occur during adipocyte differentiation. In particular, we focus on changes induced by the antiadipogenic diarylheptanoid, which was isolated from a traditional Chinese medicine Dioscorea zingiberensis and identified as (3R,5R)-3,5-dihydroxy-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptane (1). Targeted aqueous metabolic profiling indicated that a total of 14 metabolites involved in the TCA cycle, glycolysis, amino acid metabolism, and purine catabolism participate in regulating energy metabolism, lipogenesis, and lipolysis in adipocyte differentiation and can be modulated by diarylheptanoid 1. As indicated by lipidomics analysis, diarylheptanoid 1 restored the quantity and degree of unsaturation of long-chain free fatty acids and restored the levels of 171 lipids mainly from 10 lipid classes in adipocytes. In addition, carbohydrate metabolism in diarylheptanoid-1-treated adipocytes further demonstrated the delayed differentiation process by flux analysis. Our results provide valuable information for further understanding the metabolic adjustment in adipocytes subjected to diarylheptanoid 1 treatment. Moreover, this study offers new insight into developing antiadipogenic leading compounds based on metabolomics.

    Original languageEnglish (US)
    Pages (from-to)2092-2101
    Number of pages10
    JournalJournal of Proteome Research
    Volume17
    Issue number6
    DOIs
    StatePublished - Jun 1 2018

    Fingerprint

    Diarylheptanoids
    Metabolomics
    Adipocytes
    Lipids
    Obesity
    Medical problems
    Metabolites
    Nonesterified Fatty Acids
    Dioscorea
    Metabolism
    Medicine
    Lipogenesis
    Lipolysis
    Chinese Traditional Medicine
    Carbohydrate Metabolism
    Glycolysis
    Fats
    Fluxes
    Energy Metabolism
    Amino Acids

    Keywords

    • 3T3-L1 adipocyte
    • antiadipogenic
    • diarylheptanoids
    • Dioscorea zingiberensis
    • GC-MS
    • LC-MS
    • metabolic flux
    • metabolomics

    ASJC Scopus subject areas

    • Biochemistry
    • Chemistry(all)

    Cite this

    Multiplatform Metabolomics Investigation of Antiadipogenic Effects on 3T3-L1 Adipocytes by a Potent Diarylheptanoid. / Du, Dan; Gu, Haiwei; Djukovic, Danijel; Bettcher, Lisa; Gong, Meng; Zheng, Wen; Hu, Liqiang; Zhang, Xinyu; Zhang, Renke; Wang, Dongfang; Raftery, Daniel.

    In: Journal of Proteome Research, Vol. 17, No. 6, 01.06.2018, p. 2092-2101.

    Research output: Contribution to journalArticle

    Du, D, Gu, H, Djukovic, D, Bettcher, L, Gong, M, Zheng, W, Hu, L, Zhang, X, Zhang, R, Wang, D & Raftery, D 2018, 'Multiplatform Metabolomics Investigation of Antiadipogenic Effects on 3T3-L1 Adipocytes by a Potent Diarylheptanoid', Journal of Proteome Research, vol. 17, no. 6, pp. 2092-2101. https://doi.org/10.1021/acs.jproteome.8b00028
    Du, Dan ; Gu, Haiwei ; Djukovic, Danijel ; Bettcher, Lisa ; Gong, Meng ; Zheng, Wen ; Hu, Liqiang ; Zhang, Xinyu ; Zhang, Renke ; Wang, Dongfang ; Raftery, Daniel. / Multiplatform Metabolomics Investigation of Antiadipogenic Effects on 3T3-L1 Adipocytes by a Potent Diarylheptanoid. In: Journal of Proteome Research. 2018 ; Vol. 17, No. 6. pp. 2092-2101.
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    abstract = "Obesity is fast becoming a serious health problem worldwide. Of the many possible antiobesity strategies, one interesting approach focuses on blocking adipocyte differentiation and lipid accumulation to counteract the rise in fat storage. However, there is currently no drug available for the treatment of obesity that works by inhibiting adipocyte differentiation. Here we use a broad-based metabolomics approach to interrogate and better understand metabolic changes that occur during adipocyte differentiation. In particular, we focus on changes induced by the antiadipogenic diarylheptanoid, which was isolated from a traditional Chinese medicine Dioscorea zingiberensis and identified as (3R,5R)-3,5-dihydroxy-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptane (1). Targeted aqueous metabolic profiling indicated that a total of 14 metabolites involved in the TCA cycle, glycolysis, amino acid metabolism, and purine catabolism participate in regulating energy metabolism, lipogenesis, and lipolysis in adipocyte differentiation and can be modulated by diarylheptanoid 1. As indicated by lipidomics analysis, diarylheptanoid 1 restored the quantity and degree of unsaturation of long-chain free fatty acids and restored the levels of 171 lipids mainly from 10 lipid classes in adipocytes. In addition, carbohydrate metabolism in diarylheptanoid-1-treated adipocytes further demonstrated the delayed differentiation process by flux analysis. Our results provide valuable information for further understanding the metabolic adjustment in adipocytes subjected to diarylheptanoid 1 treatment. Moreover, this study offers new insight into developing antiadipogenic leading compounds based on metabolomics.",
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