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

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Multiplatform Metabolomics Investigation of Antiadipogenic Effects on 3T3-L1 Adipocytes by a Potent Diarylheptanoid
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2018-05-03 , DOI: 10.1021/acs.jproteome.8b00028
Dan Du _{1,

2} , Haiwei Gu _{1,

2,

3} , Danijel Djukovic ₂ , Lisa Bettcher ₂ , Meng Gong ₁ , Wen Zheng ₁ , Liqiang Hu ₁ , Xinyu Zhang ₂ , Renke Zhang ₂ , Dongfang Wang ₂ , Daniel Raftery _{2,

4}

Affiliation

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.

中文翻译：

有效二芳基庚烷类化合物对 3T3-L1 脂肪细胞抗脂肪形成作用的多平台代谢组学研究

肥胖正在迅速成为全世界一个严重的健康问题。在许多可能的抗肥胖策略中，一种有趣的方法侧重于阻止脂肪细胞分化和脂质积累，以抵消脂肪储存的增加。然而，目前还没有可用于通过抑制脂肪细胞分化来治疗肥胖的药物。在这里，我们使用基础广泛的代谢组学方法来询问并更好地了解脂肪细胞分化过程中发生的代谢变化。我们特别关注抗脂肪生成二芳基庚烷类化合物引起的变化，该物质是从传统中药薯蓣中分离出来的，并被鉴定为(3 R ,5 R )-3,5-二羟基-1-(3,4-二羟基苯基)- 7-(4-羟基苯基)-庚烷( 1 )。靶向水性代谢分析表明，共有 14 种涉及 TCA 循环、糖酵解、氨基酸代谢和嘌呤分解代谢的代谢物参与调节脂肪细胞分化中的能量代谢、脂肪生成和脂肪分解，并且可以受到二芳基庚烷类化合物的调节1。脂质组学分析表明，二芳基庚烷1恢复了脂肪细胞中长链游离脂肪酸的数量和不饱和度，并恢复了主要来自10类脂质的171种脂质的水平。此外，二芳基庚烷-1处理的脂肪细胞中的碳水化合物代谢通过通量分析进一步证明了延迟的分化过程。我们的结果为进一步了解二芳基庚烷1处理后脂肪细胞的代谢调整提供了有价值的信息。此外，这项研究为开发基于代谢组学的抗脂肪形成先导化合物提供了新的见解。

更新日期：2018-05-04

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