Publications by authors named "Hao-Jan Liang"

15 Publications

  • Page 1 of 1

Lipid changes in extrapulmonary organs and serum of rats after chronic exposure to ambient fine particulate matter.

Sci Total Environ 2021 Aug 10;784:147018. Epub 2021 Apr 10.

Institute of Environmental and Occupational Health Sciences, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan.

Fine particulate matter (PM) is able to pass through the respiratory barrier to enter the circulatory system and can consequently spread to the whole body to cause toxicity. Although our previous studies have revealed significantly altered levels of phosphorylcholine-containing lipids in the lungs of rats after chronic inhalation exposure to PM, the effects of PM on phosphorylcholine-containing lipids in the extrapulmonary organs have not yet been elucidated. In this study, we examined the lipid effects of chronic PM exposure on various organs and serum by using a rat inhalation model followed by a mass spectrometry-based lipidomic approach. Male Sprague-Dawley rats were continuously exposed at the whole body level to nonfiltered and nonconcentrated ambient air from the outside environment of Taipei city for 8 months, while the control rats inhaled filtered air simultaneously. After exposure, serum samples and various organs, including the testis, pancreas, heart, liver, kidney, spleen, and epididymis, were collected for lipid extraction and analysis to examine the changes in phosphorylcholine-containing lipids after exposure. The results from the partial least squares discriminant analysis models demonstrated that the lipid profiles in the PM exposure group were different from those in the control group in the rat testis, pancreas, heart, liver, kidney and serum. The greatest PM-induced lipid effects were observed in the testes. Decreased lyso-phosphatidylcholines (PCs) as well as increased unsaturated diacyl-PCs and sphingomyelins in the testes may be related to maintaining the membrane integrity of spermatozoa, antioxidation, and cell signaling. Additionally, our results showed that decreased PC(16:0/18:1) was observed in both the serum and testes. In conclusion, exposure to chronic environmental concentrations of PM caused lipid perturbation, especially in the testes of rats. This study highlighted the susceptibility of the testes and suggested possible molecular events for future study.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147018DOI Listing
August 2021

Lipid responses to environmental perfluoroalkyl substance exposure in a Taiwanese Child cohort.

Environ Pollut 2021 Aug 24;283:117007. Epub 2021 Mar 24.

Institute of Environmental and Occupational Health Sciences, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan. Electronic address:

Although recent epidemiologic studies have focused on some of the health effects of perfluoroalkyl substance (PFASs) exposure in humans, the associations between PFASs exposure and the lipidome in children are still unclear. The purpose of this study was to assess lipid changes in children to understand possible molecular events of environmental PFASs exposure and suggest potential health effects. A total of 290 Taiwanese children (8-10 years old) were included in this study. Thirteen PFASs were analyzed in their serum by high-performance liquid chromatography-tandem mass spectrometry (LC-MS). MS-based lipidomic approaches were applied to examine lipid patterns in the serum of children exposed to different levels of PFASs. LC coupling with triple quadrupole MS technology was conducted to analyze phosphorylcholine-containing lipids. Multivariate analyses, such as partial least squares analysis along with univariate analyses, including multiple linear regression, were used to analyze associations between s exposure and unique lipid patterns. Our results showed that different lipid patterns were discovered in children exposed to different levels of specific PFASs, such as PFTrDA, PFOS, and PFDA. These changes in lipid levels may be involved in hepatic lipid metabolism, metabolic disorders, and PFASs-membrane interactions. This study showed that lipidomics is a powerful approach to identify critical PFASs that cause metabolite perturbation in the serum of children and suggest possible adverse health effects of these chemicals in children.
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http://dx.doi.org/10.1016/j.envpol.2021.117007DOI Listing
August 2021

Longitudinal change of metabolite profile and its relation to multiple risk factors for the risk of developing hepatitis B-related hepatocellular carcinoma.

Mol Carcinog 2020 11 10;59(11):1269-1279. Epub 2020 Sep 10.

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

Despite considerable knowledge of viral pathogenesis, the pathophysiological changes related to the multifactorial, multistep process of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) development remains unclear. Longitudinal metabolomics study can reveal biological process for disease progression. We performed metabolite profiling with longitudinal prediagnostic plasma samples from two nested case-control studies of hepatitis B surface antigen carriers participating in ultrasound screening for HCC, one within a government employee cohort (870 samples from 109 HCC cases and 107 controls) and the other within a hospital-based cohort (266 samples from 63 HCC cases and 114 controls). Of the 34 measured metabolites, tyrosine, isoleucine, and glutamine were consistently associated with HCC. In analyses combining longitudinal data, a high metabolic risk score based on the three amino acids was robustly associated with increased risk of HCC (OR = 3.71, 95% confidence interval: 2.53-5.42), even after adjustment for clinical factors, or when assessed for different times up to ≥8 years before diagnosis. Similar association was observed in an independent, prospective analysis comprising 633 randomly selected individuals of the government employee cohort. More importantly, this metabolite signature was longitudinally influenced by HBV-infection phase and involved in gradual progression to liver fibrosis and cirrhosis. Furthermore, mediation analysis showed that the score mediated substantial proportions of the associations of key viral factors, insulin resistance, and diabetes status with HCC risk. Our results suggest that an amino-acid dysregulation metabotype may play a role in HBV-related HCC development, and may also be linked to common pathways that mediate increased HCC risks.
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http://dx.doi.org/10.1002/mc.23255DOI Listing
November 2020

Brain lipid profiles in the spontaneously hypertensive rat after subchronic real-world exposure to ambient fine particulate matter.

Sci Total Environ 2020 Mar 18;707:135603. Epub 2019 Nov 18.

Institute of Environmental Health, College of Public Health, National Taiwan University, Taiwan; Department of Public Health, National Taiwan University, Taiwan. Electronic address:

Recent studies have illustrated an association between ambient fine particulate matter (PM) exposure and neuronal toxicity in epidemiological studies and animal models. However, the possible molecular effects on brains under real-world exposure to PM remain unclear. In this pilot study, male spontaneously hypertensive rats were whole-bodily exposed to ambient air from the outdoor environment of Taipei City for 3 months, while the control rats inhaled HEPA-filtered air. The PM-induced phosphatidylcholine and sphingomyelin profiles in the hippocampus, cortex, medulla, cerebellum, and olfactory bulb were assessed by mass spectrometry (MS)-based lipidomics. Partial least squares discriminant analysis (PLS-DA) and the Wilcoxon rank sum test were used to examine the lipid changes between the exposed and control groups. The PLS-DA models showed that phosphatidylcholine and sphingomyelin profiles of the PM exposure group were different from those of the control group in each brain region except the cortex. More lipid changes were found in the hippocampus, while fewer lipid changes were observed in the olfactory bulb. The lipid alteration in the hippocampus may strengthen membrane integrity, modulate signaling pathways, and avoid accumulation of lipofuscin to counter the PM-induced stress. The lipid changes in the cortex and medulla may respond to PM-induced injury and inflammation; while the lipid changes in the cerebellum were associated with neuron protection. This study suggests that the MS-based lipidomics is a powerful approach to discriminate the brain lipid profiles even at the environmental level of ambient PM and has the potential to suggest possible adverse health effects in long-term PM exposure studies.
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http://dx.doi.org/10.1016/j.scitotenv.2019.135603DOI Listing
March 2020

Metabolomic Analysis of Platelets of Patients With Aspirin Non-Response.

Front Pharmacol 2019 10;10:1107. Epub 2019 Oct 10.

Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.

Aspirin is the most commonly used antiplatelet agent for the prevention of cardiovascular diseases. However, a certain proportion of patients do not respond to aspirin therapy. The mechanisms of aspirin non-response remain unknown. The unique metabolomes in platelets of patients with coronary artery disease (CAD) with aspirin non-response may be one of the causes of aspirin resistance. We enrolled 29 patients with CAD who were aspirin non-responders, defined as a study subject who were taking aspirin with a platelet aggregation time less than 193 s by PFA-100, and 31 age- and sex-matched patients with CAD who were responders. All subjects had been taking 100 mg of aspirin per day for more than 1 month. Hydrophilic metabolites from the platelet samples were extracted and analyzed by nuclear magnetic resonance (NMR). Both 1D H and 2D J-resolved NMR spectra were obtained followed by spectral processing and multivariate statistical analysis, such as partial least squares discriminant analysis (PLS-DA). Eleven metabolites were identified. The PLS-DA model could not distinguish aspirin non-responders from responders. Those with low serum glycine level had significantly shorter platelet aggregation time (mean, 175.0 s) compared with those with high serum glycine level (259.5 s). However, this association became non-significant after correction for multiple tests. The hydrophilic metabolic profile of platelets was not different between aspirin non-responders and responders. An association between lower glycine levels and higher platelet activity in patients younger than 65 years suggests an important role of glycine in the pathophysiology of aspirin non-response.
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http://dx.doi.org/10.3389/fphar.2019.01107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797853PMC
October 2019

Metabolic adaptation to feed restriction on the green sturgeon (Acipenser medirostris) fingerlings.

Sci Total Environ 2019 Sep 11;684:78-88. Epub 2019 May 11.

Department of Animal Science, University of California, Davis 95616, USA.

Food restriction may cause severe biological effects on wildlife and lead to population decline and extinction. The objective of the current study was to examine the metabolic effects on green sturgeon in response to feed restriction. Green sturgeon fingerlings were fed for two weeks at 12.5, 25, 50 and 100% of the optimum feeding rate (OFR), which corresponded to 0.25, 0.50, 1.00, and 2.00% body weight per day. We characterized the changes in hydrophilic and hydrophobic metabolites from extracts of muscle, liver, and kidney using nuclear magnetic resonance spectroscopy followed by multivariate statistical analysis. The results of principal component analysis (PCA) score plots from the analyses of hydrophilic metabolites showed that they exhibited a greater response to feed restriction than hydrophobic metabolites. In general, the hydrophilic metabolites in tissues from fish fed ≦25% of the OFR were separated from those fed 100% of the OFR in the PCA score plots. Among the three types of tissues examined, the overall metabolite changes showed a greater response to feed restriction in kidney tissue than in liver or muscle tissues. Numerous glucogenic amino acids in muscle and most amino acids in the kidney were decreased under feed restriction conditions. A significant decrease in ketone bodies (3-hydroxyisobutyrate) was observed in the muscle. Most fatty acids except for glycerol, phospholipid and cholesterol in the liver and kidney tissues were decreased under feed restriction conditions. Creatine phosphate, taurine and glycine were also significantly increased in tissues under feed restriction conditions. In conclusion, this study suggests that the manipulation of feed restriction under the current conditions perturbed metabolites related to energy metabolism, osmolality regulation, and antioxidation capacity in the sturgeon.
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http://dx.doi.org/10.1016/j.scitotenv.2019.05.044DOI Listing
September 2019

Mass spectrometry-based lipidomics to explore the biochemical effects of naphthalene toxicity or tolerance in a mouse model.

PLoS One 2018 1;13(10):e0204829. Epub 2018 Oct 1.

Institute of Environmental Health, College of Public Health, National Taiwan University, Taipei, Taiwan.

Naphthalene causes mouse airway epithelial injury. However, repeated exposures of naphthalene result in mouse airway tolerance. Previous results showed that toxicity or tolerance was correlated with changes of phosphorylcholine-containing lipids. In this study, a mass spectrometry-based lipidomic approach was applied to examine the effects of naphthalene-induced injury or tolerance in the male ICR mice. The injury model was vehicle x 7 plus 300 mg/kg naphthalene while the tolerant one was 200 mg/kg daily x 7 followed by 300 mg/kg naphthalene on day 8. The lung, liver, kidney, and serum samples were collected for profiles of phosphorylcholine-containing lipids including phosphatidylcholines (PCs) and sphingomyelins (SMs). A partial least-square-discriminate analysis model showed different lung phosphorylcholine-containing lipid profiles from the injured, tolerant, and control groups. Perturbation of diacyl-PCs and plasmenylcholines may be associated with enhanced membrane flexibility and anti-oxidative mechanisms in the lungs of tolerant mice. Additionally, alterations of lyso-PCs and SMs may be responsible for pulmonary dysfunction and inflammation in the lungs of injured mice. Moreover, serum PC(16:0/18:1) has potential to reflect naphthalene-induced airway injuries. Few phosphorylcholine-containing lipid alterations were found in the mouse livers and kidneys across different treatments. This study revealed the changes in lipid profiles associated with the perturbations caused by naphthalene tolerance and toxicity; examination of lipids in serum may assist biomarker development with the potential for application in the human population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0204829PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166967PMC
March 2019

LC-MS-based lipidomics to examine acute rat pulmonary responses after nano- and fine-sized ZnO particle inhalation exposure.

Nanotoxicology 2018 06 11;12(5):439-452. Epub 2018 Apr 11.

a Institute of Environmental Health, College of Public Health , National Taiwan University , Taipei , Taiwan.

Zinc oxide (ZnO) nano- and fine-sized particles are associated with respiratory toxicity in humans, but the underlying molecular mechanisms remain unclear. Our previous nuclear magnetic resonance-based metabolomic study demonstrated that changes in phosphorylcholine-containing lipids (PC-CLs) in the respiratory system were associated with ZnO particle-induced respiratory toxicity. However, the details of the lipid species associated with adverse effects and possible biomarker signatures have not been identified. Thus, a liquid chromatography-mass spectrometry (LC-MS)-based lipidomics platform was applied to examine the alterations of PC-CL species in the lungs of rats treated with a series of concentrations of nano-sized (35 nm) or fine-sized (250 nm) ZnO particles via inhalation. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and the Mann-Whitney U (MWU) test with false discovery rate (FDR) control were conducted to explore the perturbed lipid species and to discriminate a potential pulmonary biomarker signature after ZnO particle exposure. The PCA and PLS-DA models revealed that the fine-sized ZnO particle-treated groups and the high-concentration nano-sized group were separated from the control groups as well as from the low and moderate nano-sized groups. The results from the MWU test further suggested that after FDR adjustment, numerous PC-CL species were altered in the high-concentration and moderate-concentration fine-sized groups. Furthermore, our results suggested that lipids involved in anti-oxidation, membrane conformation, and cellular signal transduction were altered in response to ZnO-induced oxidative stress and inflammation. One lipid, PC(18:0/18:1), exhibited good performance (AUC > 0.8) of discriminative ability in distinguishing ZnO particle exposure from the control. These findings not only provide a foundation for the exploration of possible ZnO particle-mediated mechanisms but also suggest a lipid biomarker for ZnO particle exposure.
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http://dx.doi.org/10.1080/17435390.2018.1458918DOI Listing
June 2018

Nuclear magnetic resonance- and mass spectrometry-based metabolomics to study maleic acid toxicity from repeated dose exposure in rats.

J Appl Toxicol 2017 Dec 10;37(12):1493-1506. Epub 2017 Jul 10.

Institute of Environmental Health, College of Public Health, National Taiwan University, No. 17, ShiuJou Rd., Taipei, 10055, Taiwan.

Maleic acid (MA), a chemical intermediate used in many consumer and industrial products, was intentionally adulterated in a variety of starch-based foods and instigated food safety incidents in Asia. We aim to elucidate possible mechanisms of MA toxicity after repeated exposure by (1) determining the changes of metabolic profile using H nuclear magnetic resonance spectroscopy and multivariate analysis, and (2) investigating the occurrence of oxidative stress using liquid chromatography tandem mass spectrometry by using Sprague-Dawley rat urine samples. Adult male rats were subjected to a 28 day subchronic study (0, 6, 20 and 60 mg kg ) via oral gavage. Urine was collected twice a day on days 0, 7, 14, 21 and 28; organs underwent histopathological examination. Changes in body weight and relative kidney weights in medium- and high-dose groups were significantly different compared to controls. Morphological alterations were evident in the kidneys and liver. Metabolomic results demonstrated that MA exposure increases the urinary concentrations of 8-hydroxy-2'-deoxyguanosine, 8-nitroguanine and 8-iso-prostaglandin F ; levels of acetoacetate, hippurate, alanine and acetate demonstrated time- and dose-dependent variations in the treatment groups. Findings suggest that MA consumption escalates oxidative damage, membrane lipid destruction and disrupt energy metabolism. These aforementioned changes in biomarkers and endogenous metabolites elucidate and assist in characterizing the possible mechanisms by which MA induces nephro- and hepatotoxicity.
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http://dx.doi.org/10.1002/jat.3500DOI Listing
December 2017

Use of nuclear magnetic resonance-based metabolomics to characterize the biochemical effects of naphthalene on various organs of tolerant mice.

PLoS One 2015 7;10(4):e0120429. Epub 2015 Apr 7.

Department of Pediatrics, National Taiwan University Hospital, Taipei 100, Taiwan; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei 100, Taiwan.

Naphthalene, the most common polycyclic aromatic hydrocarbon, causes airway epithelium injury in mice. Repeated exposure of mice to naphthalene induces airway epithelia that are resistant to further injury. Previous studies revealed that alterations in bioactivation enzymes and increased levels of gamma-glutamylcysteine synthase in the bronchioles protect tolerant mice from naphthalene and its reactive metabolites. In our current study, tolerance was induced in male ICR mice using a total of 7 daily intraperitoneal injections of naphthalene (200 mg/kg). Both naphthalene-tolerant and non-tolerant mice were challenged with a dose of 300 mg/kg naphthalene on day 8 to investigate metabolite differences. The lungs, liver, and kidneys were collected for histopathology 24 h after the challenge dose. Bronchial alveolar lavage fluid (BALF) and both hydrophilic and hydrophobic extracts from each organ were analyzed using nuclear magnetic resonance (NMR)-based metabolomics. The histological results showed no observable injuries to the airway epithelium of naphthalene-tolerant mice when compared with the control. In contrast, airway injuries were observed in mice given a single challenge dose (injury mice). The metabolomics analysis revealed that the energy metabolism in the lungs of tolerant and injury mice was significantly perturbed. However, antioxidant metabolites, such as glutathione and succinate, were significantly increased in the lungs of tolerant mice, suggesting a role for these compounds in the protection of organs from naphthalene-induced electrophilic metabolites and free radicals. Damage to the airway cellular membrane, as shown by histopathological results and increased acetone in the BALF and perturbation of hydrophobic lung extracts, including cholesterol, phosphorylcholine-containing lipids, and fatty acyl chains, were observed in injury mice. Consistent with our histopathological results, fewer metabolic effects were observed in the liver and kidney of mice after naphthalene treatments. In conclusion, NMR-based metabolomics reveals possible mechanisms of naphthalene tolerance and naphthalene-induced toxicity in the respiratory system of mice.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0120429PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388704PMC
April 2016

NMR- and MS-based metabolomics: various organ responses following naphthalene intervention.

Mol Biosyst 2014 Jul 7;10(7):1918-31. Epub 2014 May 7.

Graduate Institute of Toxicology, College of Medicine, National Taiwan University, No.1, Sec. 1, Jen-ai Rd., Taipei 100, Taiwan.

Naphthalene, a polycyclic aromatic hydrocarbon, is a ubiquitous environmental pollutant capable of causing illness. In this study, we deconvoluted the metabolites related to naphthalene intervention in various organs by using nuclear magnetic resonance (NMR) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Male ICR mice were intraperitoneally dosed with olive oil (vehicle), and a low dose and a high dose (100 and 200 mg kg(-1) body wt, respectively) of naphthalene. After 48 h, the lungs, liver, and kidneys were collected for analysing the metabolic responses. The metabolites were extracted and non-targeted profiled using NMR. Low NMR resolution limited the identification of the hydrophobic metabolites. Therefore, LC-MS/MS-based focus lipidomics was applied to profile phosphorylcholine-containing lipids and sphingolipids. Chemometric analysis revealed that succinate and lactate were significantly increased in the lungs, suggesting that energy metabolisms and antioxidation were increased following naphthalene treatment. In the liver, anti-oxidative stress-related metabolites increased, enabling the oxidative stress during naphthalene biotransformation and detoxification to be overcome. The elevation of glutathione protected kidneys from reactive-naphthalene-metabolite-induced injury. Significant alteration of hydrophobic metabolites (membrane constituents) revealed lung and liver were the target organs of naphthalene treatment. MS data demonstrated that phosphatidylcholine (PC) and ceramide species were significantly altered in the lungs and liver, whereas only PC was observed in the kidneys. Elevated numbers of unsaturated bonds and fatty acyl chains in both ceramides and PCs were determined to reduce cellular membrane rigidity and facilitating the trafficking of recovery elements into the cell for rejuvenation. To conclude, the complementary results of NMR- and MS-based metabolomics enabled the characterization of naphthalene-induced changes in various organs.
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http://dx.doi.org/10.1039/c4mb00090kDOI Listing
July 2014

Two-dimensional LC-MS/MS to enhance ceramide and phosphatidylcholine species profiling in mouse liver.

Biomed Chromatogr 2014 Sep 2;28(9):1284-93. Epub 2014 Apr 2.

Graduate Institute of Toxicology, College of Medicine, National Taiwan University, No. 1, Sec. 1, Jen-ai Rd, Taipei, 100, Taiwan; Institute of Environmental Health, College of Public Health, National Taiwan University, No. 17, Xu-zhou Rd, Taipei, 100, Taiwan.

A two-dimensional (2D) hydrophilic interaction liquid chromatography (HILIC) and reverse-phase (RP) liquid chromatography (LC) system coupled with triple-quadrupole mass spectrometry (MS) was developed to comprehensively profile ceramides and phosphatidylcholine in extracted biological samples. Briefly, the 2D HILIC-RPLC system used a silica HILIC column operated in the first dimension to distinguish the lipid classes and a BEH C18 column operated in the second dimension to separate the lipid species of the same class. The regression linearity of each lipid was satisfactory in both systems; however, the absolute matrix effect factor was reduced in 2D LC-MS/MS system. Limits of detection of 2D LC-MS/MS system were 2- to 3-fold lower compared with one-dimensional RPLC-MS/MS. The recovery from the sample ranged from 84.5 to 110%. To summarize, the developed method was proven to be accurate and producible, as relative standard deviations remained <20% at three spiked levels. The efficiency of this newly developed system was applied to measure changes of lipids in the liver of mice after naphthalene treatment. Orthogonal projection to latent structures-discriminant analysis discriminated the lipids from control and the treatment group. We concluded that 2D LC-MS/MS is a promising method to assist lipidomic studies of complex biological samples.
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http://dx.doi.org/10.1002/bmc.3162DOI Listing
September 2014

Characterization of the biochemical effects of naphthalene on the mouse respiratory system using NMR-based metabolomics.

J Appl Toxicol 2014 Dec 30;34(12):1379-88. Epub 2014 Jan 30.

Institute of Environmental Health, College of Public Health, National Taiwan University, Taipei, 10055, Taiwan, Republic of China.

Naphthalene is a ubiquitous environmental pollutant to which humans are exposed. Previous studies have demonstrated that naphthalene causes bronchiolar epithelial necrosis in the mouse distal airway, after parenteral administration. In this study, metabolic variations in the bronchoalveolar lavage fluid (BALF) and the lung tissues of naphthalene-treated mice and controls were examined using nuclear magnetic resonance (NMR)-based metabolomics to identify the toxic mechanism. Male ICR mice were treated with naphthalene [0, 50, 100 and 200 mg kg(-1), intraperitoneally (i.p.)]. After 24 h, BALF and lung tissues were collected and prepared for (1)H and J-resolved (JRES) NMR analysis after principal component analysis (PCA). PCA modeling of p-JRES spectra from the BALF, as well as hydrophilic and hydrophobic lung metabolites, enabled the high-dose group to be discriminated from the control group; increased levels of isopropanol, ethane, and acetone and lower levels of ethanol, acetate, formate, and glycerophosphocholine were detected in the BALF of mice treated with higher doses of naphthalene. Furthermore, increased isopropanol and phosphorylcholine-containing lipid levels and decreased succinate and glutamine levels were discovered in the lungs of naphthalene-exposed mice. These metabolic changes may be related to lipid peroxidation, disruptions of membrane components and imbalanced energy supply, and these results may partially explain the loss of cell membrane integrity in the airway epithelial cells of naphthalene-treated mice. We conclude that NMR-based metabolomic studies on BALF and lung tissues are a powerful tool to understand the mechanisms underlying respiratory toxicity.
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http://dx.doi.org/10.1002/jat.2970DOI Listing
December 2014

Association between the metabolome and low bone mineral density in Taiwanese women determined by (1)H NMR spectroscopy.

J Bone Miner Res 2014 Jan;29(1):212-22

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

Osteoporosis is related to the alteration of specific circulating metabolites. However, previous studies on only a few metabolites inadequately explain the pathogenesis of this complex syndrome. To date, no study has related the metabolome to bone mineral density (BMD), which would provide an overview of metabolism status and may be useful in clinical practice. This cross-sectional study involved 601 healthy Taiwanese women aged 40 to 55 years recruited from MJ Health Management Institution between 2009 and 2010. Participants were classified according to high (2nd tertile plus 3rd tertile) and low (1st tertile) BMD groups. The plasma metabolome was evaluated by proton nuclear magnetic resonance spectroscopy ((1) H NMR). Principal components analysis (PCA), partial least-squares discriminant analysis (PLS-DA), and logistic regression analysis were used to assess the association between the metabolome and BMD. The high and low BMD groups could be differentiated by PLS-DA but not PCA in postmenopausal women (Q(2)  = 0.05, ppermutation  = 0.04). Among postmenopausal women, elevated glutamine was significantly associated with low BMD (adjusted odds ratio [AOR] = 5.10); meanwhile, elevated lactate (AOR = 0.55), acetone (AOR = 0.51), lipids (AOR = 0.04), and very low-density lipoprotein (AOR = 0.49) protected against low BMD. To the best of our knowledge, this study is the first to identify a group of metabolites for characterizing low BMD in postmenopausal women using a (1) H NMR-based metabolomic approach. The metabolic profile may be useful for predicting the risk of osteoporosis in postmenopausal women at an early age.
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http://dx.doi.org/10.1002/jbmr.2018DOI Listing
January 2014
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