Method for liver tissue metabolic profiling study and its application in type 2 diabetic rats based on ultra performance liquid chromatography–mass spectrometry

Huang, Qiang; Yin, Peiyuan; Wang, Jing; Chen, Jing; Kong, Hongwei; Xu, Guowang

doi:10.1016/j.jchromb.2011.03.009

Cited by 40 publications

(30 citation statements)

References 35 publications

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“…These changes are consistent with increased deamination of amino acids used for gluconeogenesis [34]. The findings are also supported by a study in T2D rats and streptozotocin-induced diabetic rats (a type I diabetes model) [35,36]. The metabolic effect of the PPARγ activation and PPARδ activation in regulating metabolism in adipose tissue and insulin sensitivity was well-defined in vivo in white adipose tissue from ob/ob mice (mice homozygous for the obese spontaneous mutation of leptin gene) and in vitro in cultured 3T3-L1 adipocytes using 1 H NMR and MS metabolomics.…”

Section: Introductionsupporting

confidence: 80%

Metabolomic analyses for atherosclerosis, diabetes, and obesity

Virtue

Wang

et al. 2013

Biomark Res

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Insulin resistance associated with type 2 diabetes mellitus (T2DM), obesity, and atherosclerosis is a global health problem. A portfolio of abnormalities of metabolic and vascular homeostasis accompanies T2DM and obesity, which are believed to conspire to lead to accelerated atherosclerosis and premature death. The complexity of metabolic changes in the diseases presents challenges for a full understanding of the molecular pathways contributing to the development of these diseases. The recent advent of new technologies in this area termed “Metabolomics” may aid in comprehensive metabolic analysis of these diseases. Therefore, metabolomics has been extensively applied to the metabolites of T2DM, obesity, and atherosclerosis not only for the assessment of disease development and prognosis, but also for the biomarker discovery of disease diagnosis. Herein, we summarize the recent applications of metabolomics technology and the generated datasets in the metabolic profiling of these diseases, in particular, the applications of these technologies to these diseases at the cellular, animal models, and human disease levels. In addition, we also extensively discuss the mechanisms linking the metabolic profiling in insulin resistance, T2DM, obesity, and atherosclerosis, with a particular emphasis on potential roles of increased production of reactive oxygen species (ROS) and mitochondria dysfunctions.

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Section: Introductionsupporting

confidence: 80%

Metabolomic analyses for atherosclerosis, diabetes, and obesity

Virtue

Wang

et al. 2013

Biomark Res

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“…Validations of method, including linearity, precision, stability, and recovery, were also carried out (18), which indicates that this tissue metabolomics method is reliable. Furthermore, the PCA score plot ( Supplementary Fig.…”

Section: Metabolic Profiling Of Liver Tissuesmentioning

confidence: 94%

“…The details of the metabolic profiling method, including sample preparation, metabolite extraction, and LC/MS analysis, were reported in our previous study (18). Supplementary Fig.…”

Section: Metabolic Profiling Of Liver Tissuesmentioning

confidence: 99%

Metabolic Characterization of Hepatocellular Carcinoma Using Nontargeted Tissue Metabolomics

et al. 2013

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Hepatocellular carcinoma has a poor prognosis due to its rapid development and early metastasis. In this report, we characterized the metabolic features of hepatocellular carcinoma using a nontargeted metabolic profiling strategy based on liquid chromatography-mass spectrometry. Fifty pairs of liver cancer samples and matched normal tissues were collected from patients having hepatocellular carcinoma, including tumor tissues, adjacent noncancerous tissues, and distal noncancerous tissues, and 105 metabolites were filtered and identified from the tissue metabolome. The principal metabolic alternations in HCC tumors included elevated glycolysis, gluconeogenesis, and b-oxidation with reduced tricarboxylic acid cycle and D-12 desaturase. Furthermore, increased levels of glutathione and other antioxidative molecules, together with decreased levels of inflammatory-related polyunsaturated fatty acids and phospholipase A2, were observed. Differential metabolite levels in tissues were tested in 298 serum specimens from patients with chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Betaine and propionylcarnitine were confirmed to confer good diagnostic potential to distinguish hepatocellular carcinoma from chronic hepatitis and cirrhosis. External validation of cirrhosis and hepatocellular carcinoma serum specimens further showed that this combination biomarker is useful for diagnosis of hepatocellular carcinoma with a supplementary role to a-fetoprotein. Cancer Res; 73(16); 4992-5002. Ó2013 AACR.

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“…Here, we mainly tested MeOH and ACN at different percentages owing to their popularity in studies of metabolite extraction, such as untargeted metabolite extraction in liver tissue (Masson et al, 2010), a metabolic profiling study for type 2 diabetic rats (Huang et al, 2011) and comprehensive metabolomic analysis of human steatotic liver tissue (Garcia-Canaveras et al, 2011). The extracted metabolites using the optimal protocol cover the endogenous metabolites related to liver injury, which may be useful for metabolomics analysis of hepatotoxicity.…”

Section: Discussionmentioning

confidence: 99%

“…Five extraction solvents were chosen, designed and compared for liver metabolite extraction based on previous studies(Huang et al, 2011;Liu et al, 2015;Masson, Alves, Ebbels, Nicholson, & Want, 2010). Five extraction solvents were chosen, designed and compared for liver metabolite extraction based on previous studies(Huang et al, 2011;Liu et al, 2015;Masson, Alves, Ebbels, Nicholson, & Want, 2010).…”

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confidence: 99%

Optimization of extraction and analytical protocol for mass spectrometry‐based metabolomics analysis of hepatotoxicity

Yang

Zhao

et al. 2018

Biomedical Chromatography

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Drug-induced liver injury is a clinically leading side-effect of drugs. In the present study, a liquid chromatography mass spectrometry-based metabolomics protocol was optimized for extraction and analysis of endogenous metabolites from liver tissue during hepatotoxicity. Various extraction solutions, resuspension solutions, extraction folds and dissolution methods for the supernatant were compared using the number of extracted total ions, relative response and relative extraction efficiency of targeted metabolites from liver tissue. The polar and nonpolar endogenous metabolites associated with liver injury were analyzed by hydrophilic interaction chromatography and reversed-phase liquid chromatography with UPLC-QTOFMS. The results indicated that extraction with 10-fold 50% acetonitrile in water and the supernatant diluted (1:1) with 100% acetonitrile rather than resuspension was the optimal extraction protocol. Subsequently, the optimized method was able to examine the change in metabolites in mouse liver tissue resulting from treatment with a toxic natural product, toosendanin. Taken together, the optimized extraction and analytical protocol provides high reliability and reproducibility for polar and nonpolar metabolites in liver tissue and may be suitable for metabolomics analysis of liver injury induced by drugs or chemicals.

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Method for liver tissue metabolic profiling study and its application in type 2 diabetic rats based on ultra performance liquid chromatography–mass spectrometry

Cited by 40 publications

References 35 publications

Metabolomic analyses for atherosclerosis, diabetes, and obesity

Metabolomic analyses for atherosclerosis, diabetes, and obesity

Metabolic Characterization of Hepatocellular Carcinoma Using Nontargeted Tissue Metabolomics

Optimization of extraction and analytical protocol for mass spectrometry‐based metabolomics analysis of hepatotoxicity

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