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RESUMEN La obesidad es un importante factor de riesgo cardiovascular. No obstante, no todas las personas obesas tienen un perfil metabólico alterado ni todas las personas normo-peso poseen un perfil metabólico normal. Objetivo: determinar la prevalencia de diferentes fenotipos metabólicos asocia-dos al estado nutricional en Chile. Métodos: se incluyeron 1.733 participantes de la Encuesta Nacional de Salud 2009-2010. El estado nutricional (obesidad o normo-peso) fue determinado a través del IMC mientras que la condición metabólica (saludable o no) en base a cuatro parámetros: glicemia, presión arterial, colesterol HDL y triglicéridos. Con estos parámetros de determinaron 4 fenotipos, entre ellos, MUNO: metabólicamente no saludable no obeso y MHO: obeso metabólicamente saludable. Resultados: La prevalencia de MHO fue de 3,3% mientras que un 17,4% presentaba MUNO. Adicionalmente, la prevalencia de MHO disminuyó en la medida que aumentó la edad y la mayor proporción de individuos metabólicamente saludables se encontraba en el grupo de altos ingresos y con un nivel educacional superior (técnico-universitario). Conclusión: Se evidencia una baja prevalencia de MHO, así como también una alta prevalencia de individuos MUNO en la población chilena. Futuras acciones preventivas deberían no sólo considerar el estado nutricional sino también la condición metabólica de la población.
ABSTRACT Obesity is an important cardiovascular risk factor. However, not all obese individuals have an unhealthy metabolic pro-file and vice versa. Therefore, the aim of this study was to determine the prevalence of different metabolic phenotypes by nutritional status in Chile. Methods: 1,733 individuals from the National Health Survey 2009-10 were included in this study. Nutritional status (obesity or normal-weight) was determined by BMI whereas metabolic profile was determined through four parameters: Glycaemia, blood pressure, HDL cholesterol and triglycerides. Four metabolic phenotypes were derived, among them: MUNO: metabolically unhealthy and non-obese and MHO: metabolically healthy obesity. Results: The prevalence of MHO in the Chilean population was 3.3% while the prevalence of MUNO was 17.4%. Moreover, the prevalence of MHO decreased as age increased and a greater proportion of metabolically healthy individuals were in the highest gross income group and in the technical-university educational level. Conclusion: This study shows a low prevalence of MHO and a higher prevalence of MUNO in the Chilean population. Future preventive actions should take into account not only the nutritional status, but also the metabolic profile of the population.
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Humans , Phenotype , Cardiovascular Diseases , Obesity, Metabolically Benign , Obesity , Chile , Prevalence , Risk FactorsABSTRACT
Objective Urinary metabolomics associated with the histological progression of liver fibrosis (LF) and pulmonary fibrosis (PF) were utilized to explore common differential metabolites and their associated changes, and to explain the scientific connotation of the traditional Chinese medicine (TCM) theory of "homotherapy for heteropathy". Methods HE staining was used to monitor the histopathological changes in rats with LF and PF. Urinary metabolic profiling was performed by UPLC-Q-TOF/MS to analyze the metabolic profiles of LF and PF, as well as to clarify the common differential metabolites and their dynamic changes in LF and PF progression. Results Similar pathologic processes and trajectories of the PLS-DA score plots were observed in both the LF and PF models. Furthermore, 16 differential urine metabolites were found both in LF and PF. Among these, nine metabolites, including adrenochrome and 5-L-glutamyl-taurine, were key biomarkers which affect the development of LF and PF through oxidative damage, inflammation, and release of profibrogenic cytokines. Conclusion Metabonomic analysis revealed that LF and PF share common differential metabolites with the same changing trends and explained the scientific connotation of the TCM theory of "homotherapy for heteropathy".
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The metabolic profile of bile acids (MPBA) is an indicator that reflecting the varieties, contents and variations of biological bile acids (BAs). Many kinds of detection techniques can be used to detect different kinds of BAs in different tissues. By using various detection techniques, the MPBA has been applied in various diseases such as hepatobiliary diseases, gastrointestinal diseases, metabolic diseases and nervous system diseases and so on. In this paper, we reviewed the process of BAs synthesis and metabolism and analyzed the detection techniques of BAs in different tissues and the corresponding MPBA. At the same time, we summarized the application of BAs metabolism in related diseases. The MPBA provides a reference for the diagnosis and treatment of some diseases and it has certain advantages in disease diagnosis and curative effects evaluation, which worth further study.
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Tanreqing (TRQ), a traditional Chinese medicine (TCM) formula, can alleviate liver injury and improve liver function. Its pharmacological mechanisms of actions are still unclear due to its complex components and multi-target natures. Metabolomic study is an effective approach to investigating drug pharmacological actions, new diagnostic markers, and potential mechanisms of actions. In the present study, a new strategy was used to evaluate the protective effect of TRQ capsule against carbon tetrachloride (CCl)-induced hepatotoxicity in rats, by analyzing metabolic profiling of endogenous bile acids (BAs) along with biochemical and histological analyses. BAs concentrations were determined by ultra-performance liquid chromatography coupled with quadrupole mass spectrometry (UPLC-MS). Principal component analysis and partial least squares discriminant analysis were then employed to analyze the UPLC-MS results and compare the hepatoprotective effect of TRQ capsule in different groups at the doses of 0.36, 1.44, and 2.88 g·kg body weight, respectively. Moreover, our results suggested that taurocholic acid (TCA) and taurohyodesoxycholic acid (THDCA) were the most important biochemical markers, which were indicative of CCl-induced acute hepatic damage and hepatoprotective effect of TRQ capsule. Therefore, this new strategy would be an excellent alternative method for evaluating hepatoprotective effect and proposing potential mechanisms of action for other drugs as well.
Subject(s)
Animals , Female , Male , Rats , Alanine Transaminase , Blood , Aspartate Aminotransferases , Blood , Bile Acids and Salts , Blood , Metabolism , Biomarkers , Blood , Carbon Tetrachloride , Pharmacology , Chemical and Drug Induced Liver Injury , Drug Therapy , Metabolism , Pathology , Chromatography, Liquid , Drugs, Chinese Herbal , Chemistry , Pharmacology , Therapeutic Uses , Liver , Pathology , Mass Spectrometry , Metabolome , Metabolomics , Rats, Wistar , Taurocholic Acid , Blood , Taurodeoxycholic Acid , BloodABSTRACT
Objective To study the characteristics of hyperphenylalaninemia (HPA) and the differences in blood and urine metabolic index and their correlation.Methods A total of 137 patients with HPA diagnosed by the Pediatric Inherit Metabolism and Endocrine Department,Guangdong Women and Children's Hospital,Guangzhou Medical University from January 2014 to June 2017,were enrolled.Tandem mass spectrometry (MS/MS),gas chromatography/ mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) were used to analyze the concentration of blood and urine metabolites in children,and the patients were divided into different groups according to the drug load test of tetrahydrobiopterin (BH4) and dihydrobiopterindine reductase (DHPR) deficiency.The HPA metabolite analysis of horizontal concentration by statistical differences and correlation analysis were performed.Results Among the 137 cases of HPA,there were 101 cases (73.7％) of phenylalanine hydroxylase deficiency (PAH),and among them 21 cases (15.3％) were classic phenylketonuria (PKU),37 cases were mild PKU (27.0％),43 cases (31.4％) wcrc mild HPA.Thcrc were 22 cases (16.1％) with BH4 reaction,and 79 cases (57.7％) of non-reactive type.Besides,there were 36 cases (26.3％) of tetrahydrobiopterin deficiency (BH4 D),of which 6-pyruvoyl tetrahydropterin synthase deficiency (PTPS) in 34 cases (24.8％) and dihydrobiopterindine reductase deficiency (DHPR) in 2 cases (1.5％).Urinary phenylacetic acid (r =0.673,P ＜ 0.01),phenyllactic acid (r =0.736,P ＜ 0.01),phenylpyruvic acid (r =0.642,P ＜ 0.01) were significantly correlated with blood phenylalanine (Phe) concentration,and the neopterin (N) (r =0.442,P ＜ 0.01) and biopterin (B) (r =0.398,P ＜ 0.01) had low correlation.Urinary phenylacetic acid,phenyllactic acid and phenylpyruvic acid had no correlation with urinary pterin.There were significant differences among PTPS deficiency group,BH4 response type,and non-reactive type(all P ＜ 0.05),but no significant difference between the BH4 reaction type and the non-reactive group (P ＞ 0.05).Conclusions Through the analysis of the different types of HPA metabolic profiles,it can help to master the incidence and characteristics in the region,within a certain concentration range of blood Phe,the phenylacetic acid,phenyllactic acid,phenylpyruvic acid should not be tested by GC-MS alone.Uterine erythropoietin analysis of BH4D classification and identification of BH4 reaction,non-reactive PKU have a supporting role,so master the metabolic index of various types of concentration and relevance of HPA,it can provide basis for early diagnosis,accurate treatment and follow-up.
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A metabolic profiling analysis method for metabolomic studies of rice leaf was established based on HSS T3 combined with XBridge Amide Q-TOF LC/MS by comparing the influences of different extraction methods in rice leaves of metabolites. The extraction and separation of rice leaf metabolites using three different methods including methanol-chloroform-water,methanol-chloroform-ammonia,methanol-methyl tert-butyl ether -water and different chromatographic systems were compared by the numbers of peaks, identified metabolites and the metabolic pathways. The results showed that the method of methanol-chloroform-water reached the highest coverage rate of metabolites in rice leaves,and the maximum number of unique metabolites including prephenic acid, luteolin, α-linolenic acid, aconitic acid, gibberellin A12 aldehyde, isovitexin, L-Glutamate were detected. Metabolites with different polarity in rice leaf could be detected by HSS T3 and XBridge Amide. A total of 16 kinds of organic acids, 17 kinds of nucleotides, 21 kinds of amino acids, 66 kinds of fatty acids,11 kinds of phospholipids and 7 kinds of sphingolipids were identified. XBridge Amide had an absolute advantage in detecting phospholipids and sphingolipids. The metabolic pathways involved purine metabolism, pyrimidine metabolism, tricarboxylic acid cycle, arginine metabolism, fatty acid metabolism, phospholipid metabolism, sphingolipid metabolism, phenylalanine metabolism and vitamin B2 synthesis. It showed certain complementarity between the two columns in identifying metabolites and involved the metabolic pathways. The established method is expected to be useful for the metabolomic studies of rice.
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Tanreqing (TRQ), a traditional Chinese medicine (TCM) formula, can alleviate liver injury and improve liver function. Its pharmacological mechanisms of actions are still unclear due to its complex components and multi-target natures. Metabolomic study is an effective approach to investigating drug pharmacological actions, new diagnostic markers, and potential mechanisms of actions. In the present study, a new strategy was used to evaluate the protective effect of TRQ capsule against carbon tetrachloride (CCl)-induced hepatotoxicity in rats, by analyzing metabolic profiling of endogenous bile acids (BAs) along with biochemical and histological analyses. BAs concentrations were determined by ultra-performance liquid chromatography coupled with quadrupole mass spectrometry (UPLC-MS). Principal component analysis and partial least squares discriminant analysis were then employed to analyze the UPLC-MS results and compare the hepatoprotective effect of TRQ capsule in different groups at the doses of 0.36, 1.44, and 2.88 g·kg body weight, respectively. Moreover, our results suggested that taurocholic acid (TCA) and taurohyodesoxycholic acid (THDCA) were the most important biochemical markers, which were indicative of CCl-induced acute hepatic damage and hepatoprotective effect of TRQ capsule. Therefore, this new strategy would be an excellent alternative method for evaluating hepatoprotective effect and proposing potential mechanisms of action for other drugs as well.
Subject(s)
Animals , Female , Male , Rats , Alanine Transaminase , Blood , Aspartate Aminotransferases , Blood , Bile Acids and Salts , Blood , Metabolism , Biomarkers , Blood , Carbon Tetrachloride , Pharmacology , Chemical and Drug Induced Liver Injury , Drug Therapy , Metabolism , Pathology , Chromatography, Liquid , Drugs, Chinese Herbal , Chemistry , Pharmacology , Therapeutic Uses , Liver , Pathology , Mass Spectrometry , Metabolome , Metabolomics , Rats, Wistar , Taurocholic Acid , Blood , Taurodeoxycholic Acid , BloodABSTRACT
A method based on gas chromatography-mass spectrometry (GC-MS) was established to analyze the changes of intracellular metabolites and study the toxic mechanisms of different concentrations of particulate matter (PM2.5) effecting the lung tissues in mice.Nasal drip experiments of PM2.5 suspensions (0, 7.5, 20.0, 37.5 g/L) for mice were carried out, and the intracellular metabolites in lung tissues were extracted, pretreated and analyzed.Principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) were employed for pattern recognition, and an obvious distinction among different conditions was found.According to the PLS-DA loading diagram and variable important factor (VIP) value, 7 kinds of potential biomarkers, alanine, valine, leucine, ornithine, fumaric acid, citric acid and purine (p<0.01), were determined with significant differences between four different concentrations of PM2.5.Metabolic pathway analysis indicated that the oxidative stress reactions were enhanced, and the TCA cycle and the purine metabolism in lung cells were restrained after dripping PM2.5 to the lung tissues in mice.This study could provide a new perspective and theoretical basis for the further analysis on toxic mechanisms by PM2.5.
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Objective · To explore the change of metabolomic profiling after erlotinib (anepithelial growth factor receptor tyrosine kinase inhibitor)resistance of lung adenocarcinoma cells (PC9-ER), and find the differential metabolome associated witherlotinib resistance. Methods · Metabolic profiling of PC9-ER cells and homologous parent PC9 cells was acquired by the ultraperformance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The data were analyzed by multi-dimensional statistical methods, such as partial least squares projection to latent structures-discriminant analysis (PLS-DA), to select and identify differential metabolites associated with erlotinib resistance. Results · A total of 14 differential metabolites were identified in PC9-ER cells. Seven up-regulated metabolites included N-acetylspermidine, phosphatidylethanolamine, AMP, pantothenic acid,proline, glutamate, and histidine, while seven down-regulated metabolites included citrulline, phosphorylcholine, glutathione, cysteinylglycine, glutathione oxidized, NAD, and S-adenosylmethionine, mainly participating in glutathione metabolism, glutamate metabolism, ammonia recycling, and protein biosynthesis. Conclusion · Metabolic profiling of erlotinib-resistant lung adenocarcinoma cells was changed. The information of differential metabolites associated with erlotinib resistance could provide clues for new resistance mechanisms and potential metabolism-related drug targets.
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The term "omics" refers to any type of specific study that provides collective information on a biological system. Representative omics includes genomics, proteomics, and metabolomics, and new omics is constantly being added, such as lipidomics or glycomics. Each omics technique is crucial to the understanding of various biological systems and complements the information provided by the other approaches. The main strengths of metabolomics are that metabolites are closely related to the phenotypes of living organisms and provide information on biochemical activities by reflecting the substrates and products of cellular metabolism. The transcriptome does not always correlate with the proteome, and the translated proteome might not be functionally active. Therefore, their changes do not always result in phenotypic alterations. Unlike the genome or proteome, the metabolome is often called the molecular phenotype of living organisms and is easily translated into biological conditions and disease states. Here, we review the general strategies of mass spectrometry-based metabolomics. Targeted metabolome or lipidome analysis is discussed, as well as nontargeted approaches, with a brief explanation of the advantages and disadvantages of each platform. Biomedical applications that use mass spectrometry-based metabolomics are briefly introduced.
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Complement System Proteins , Genome , Genomics , Glycomics , Mass Spectrometry , Metabolism , Metabolome , Metabolomics , Phenotype , Proteome , Proteomics , TranscriptomeABSTRACT
Objective: To compare the metabolic profiling of Vladimiriae Radix (VR) before and after simmer processing and to screen out the characteristic constituents leading to some differences. Methods: The chromatogram data sets of the processed and unprocessed VR were obtained by HPLC-UV analysis; The metabolic profiling differences of VR before and after processing were compared by principal component analysis, partial least square-discriminant analysis, and hierarchical cluster analysis, then the characteristic constituents were screened out. Results: The metabolic profilings between processed and unprocessed VR were apparently different, and the data showed seven constituents among them mainly made the quality difference, including costunolide and dehydrocostus lactone. Conclusion: The processed and unprocessed VR have the significant differences on the metabolic profiling.