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Kenji Yamada, Hironori Kobayashi, Ryosuke Bo, Jamiyan Purevsuren, Yuichi Mushimoto, Tomoo Takahashi, Yuki Hasegawa, Takeshi Taketani, Seiji Fukuda, Seiji Yamaguchi
INTRODUCTION: We evaluated the effects of bezafibrate (BEZ) on β-oxidation in fibroblasts obtained from patients with glutaric acidemia type II (GA2) of various clinical severities using an in vitro probe (IVP) assay. METHODS: Cultured fibroblasts from 12 patients with GA2, including cases of the neonatal-onset type both with and without congenital anomalies (the prenatal- and neonatal-onset forms, respectively), the infantile-onset, and the myopathic forms, were studied...
August 30, 2016: Brain & Development
Christina Boeck, Alexandra Maria Koenig, Katharina Schury, Martha Leonie Geiger, Alexander Karabatsiakis, Sarah Wilker, Christiane Waller, Harald Gündel, Jörg Michael Fegert, Enrico Calzia, Iris-Tatjana Kolassa
The experience of maltreatment during childhood is associated with chronic low-grade inflammation in adulthood. However, the molecular mechanisms underlying this pro-inflammatory phenotype remain unclear. Mitochondria were recently found to principally coordinate inflammatory processes via both inflammasome activation and inflammasome-independent pathways. To this end, we hypothesized that alterations in immune cell mitochondrial functioning and oxidative stress might be at the interface between the association of maltreatment experiences during childhood and inflammation...
September 2016: Mitochondrion
Elaine Cowan, Praveen Kumar, Kerry J Burch, David J Grieve, Brian D Green, Stewart F Graham
INTRODUCTION: Obestatin is a controversial gastrointestinal peptide purported to have metabolic actions. OBJECTIVES: This study investigated whether treatment with a stable obestatin analogue (PEG-OB(Cys(10), Cys(13))) changed plasma metabolite levels firstly in lean and subsequently in diet-induced obesity (DIO) C57BL6/J mice. METHODS: Untargeted LC-HRMS metabolomics experiments were carried out in ESI + mode with plasma extracts from both groups of animals...
2016: Metabolomics: Official Journal of the Metabolomic Society
Cynthia Roy, Pierre-Yves Tremblay, Jean-François Bienvenu, Pierre Ayotte
Metabolomics is an "omic" technique being increasingly used in epidemiological and clinical studies. We developed a method combining untargeted metabolomics with the quantitative determination of eight amino acids (AA) and eight acylcarnitines (AC) in plasma using ultra-high pressure liquid chromatography (UHPLC), electrospray ionization (ESI) and quadrupole time-of-flight mass spectrometry (QTOFMS). Separation of metabolites is performed by ion-pair reverse phase UHPLC using a HSS T3 column (2.1×100mm, 100Å, 1...
August 1, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Lian-qun Jia, Bi-xian Zhen, Xu Ying, Guan-lin Yang
OBJECTIVE: To explore metabolite profiling changes in serum of rats with pi-qi deficiency syndrome (PQDS) and pi-yang deficiency syndrome (PYDS) based on liquid chromatograph-mass spectrometer (LC-MS) technique, and to explore the essence of Pi-deficiency syndrome (PDS) from small molecule metabolite level. METHODS: Totally 21 male SD rats of SPF grade were randomly divided into three groups, the normal control group, the PQDS group, and the PYDS group, 7 in each group...
March 2016: Chinese Journal of Integrated Traditional and Western Medicine
Osama Y Al-Dirbashi, Nathan McIntosh, Pranesh Chakraborty
BACKGROUND: Newborn screening for propionic acidemia and methylmalonic acidurias using the marker propionylcarnitine (C3) is neither sensitive nor specific. Using C3 to acetylcarnitine (C3/C2) ratio, together with conservative C3 cut-offs, can improve screening sensitivity, but the false positive rate remains high. Incorporating the marker 2-methylcitric acid has been suggested, to improve the positive predictive value for these disorders without compromising the sensitivity. METHODS: Between July 2011 and December 2012 at the Newborn Screening Ontario laboratory, all neonatal dried blood spot samples that were reported as screen positive for propionic acidemia or methylmalonic acidurias based on elevated C3 and C3/C2 ratio were analyzed for 2-methylcitric acid, using liquid chromatography tandem mass spectrometry...
May 22, 2016: Journal of Medical Screening
Z Fišar, J Hroudová, N Singh, A Kopřivová, D Macečková
Some therapeutic and/or adverse effects of drugs may be related to their effects on mitochondrial function. The effects of simvastatin, resveratrol, coenzyme Q10, acetylcysteine, and acetylcarnitine on Complex I-, Complex II-, or Complex IV-linked respiratory rate were determined in isolated brain mitochondria. The protective effects of these biologically active compounds on the calcium-induced decrease of the respiratory rate were also studied. We observed a significant inhibitory effect of simvastatin on mitochondrial respiration (IC50 = 24...
2016: Folia Biologica (Praha)
Jessica A M Bastiaansen, Matthew E Merritt, Arnaud Comment
Cardiac dysfunction is often associated with a shift in substrate preference for ATP production. Hyperpolarized (HP) (13)C magnetic resonance spectroscopy (MRS) has the unique ability to detect real-time metabolic changes in vivo due to its high sensitivity and specificity. Here a protocol using HP [1-(13)C]pyruvate and [1-(13)C]butyrate is used to measure carbohydrate versus fatty acid metabolism in vivo. Metabolic changes in fed and fasted Sprague Dawley rats (n = 36) were studied at 9.4 T after tail vein injections...
2016: Scientific Reports
Marieke G Schooneman, Riekelt H Houtkooper, Carla E M Hollak, Ronald J A Wanders, Frédéric M Vaz, Maarten R Soeters, Sander M Houten
AIM: Acylcarnitines are fatty acid oxidation (FAO) intermediates, which have been implicated in diet-induced insulin resistance. Elevated acylcarnitine levels are found in obese, insulin resistant humans and rodents, and coincide with lower free carnitine. We hypothesized that increasing free carnitine levels by administration of the carnitine precursor γ-butyrobetaine (γBB) could facilitate FAO, thereby improving insulin sensitivity. METHODS: C57BL/6N mice were fed with a high fat or chow diet with or without γBB supplementation (n=10 per group)...
August 2016: Biochimica et Biophysica Acta
Cecilia Maldonado, Natalia Guevara, Cecilia Queijo, Raquel González, Pietro Fagiolino, Marta Vázquez
Blood carnitine and/or acetylcarnitine deficiencies are postulated in the literature as possible causes of higher ammonia levels. The aim of this study was to investigate if the use of valproic acid, the age of the patients, or certain central nervous system pathologies can cause carnitine and/or acetylcarnitine deficiency leading to increased ammonia levels. Three groups of patients were studied: (A) epileptic under phenytoin monotherapy (n = 31); (B) with bipolar disorder under valproic acid treatment (n = 28); (C) elderly (n = 41)...
2016: BioMed Research International
Jaroslaw Piszcz, Emily G Armitage, Alessia Ferrarini, Francisco J Rupérez, Agnieszka Kulczynska, Lukasz Bolkun, Janusz Kloczko, Adam Kretowski, Alina Urbanowicz, Michal Ciborowski, Coral Barbas
In chronic lymphocytic leukaemia (CLL), the clinical course of patients is heterogeneous. Some present an aggressive disease onset and require immediate therapy, while others remain without treatment for years. Current disease staging systems developed by Rai and Binet may be useful in forecasting patient survival time, but do not discriminate between stable and progressive forms of the disease in the early stages. Recently ample attention has been directed towards identifying new disease prognostic markers capable of predicting clinical aggressiveness at diagnosis...
April 19, 2016: Oncotarget
William E Kraus, Carl F Pieper, Kim M Huffman, Dana K Thompson, Virginia B Kraus, Miriam C Morey, Harvey J Cohen, Eric Ravussin, Leanne M Redman, James R Bain, Robert D Stevens, Christopher B Newgard
BACKGROUND: Older age and obesity are associated with metabolic dysregulation; the mechanism by which these factors impact metabolism across the lifespan is important, but relatively unknown. We evaluated a panel of amino acids (AAs) and acylcarnitines (ACs) to identify effects of age and adiposity (body mass index) on circulating small-molecule metabolites in a meta-analysis of six diverse study populations. METHODS: Targeted metabolic profiling was performed in six independent studies, representing 739 subjects with a broad range of age, body mass index, health states, and ethnic origin...
March 16, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Yonghai Lu, Ning Li, Liang Gao, Yong-Jiang Xu, Chong Huang, Kangkang Yu, Qingxia Ling, Qi Cheng, Shengsen Chen, Mengqi Zhu, Jinling Fang, Mingquan Chen, Choon Nam Ong
The identification of serum biomarkers to improve the diagnosis and prognosis of hepatocellular carcinoma has been elusive to date. In this study, we took a mass spectroscopic approach to characterize metabolic features of the liver in hepatocellular carcinoma patients to discover more sensitive and specific biomarkers for diagnosis and progression. Global metabolic profiling of 50 pairs of matched liver tissue samples from hepatocellular carcinoma patients was performed. A series of 62 metabolites were found to be altered significantly in liver tumors; however, levels of acetylcarnitine correlated most strongly with tumor grade and could discriminate between hepatocellular carcinoma tumors and matched normal tissues...
May 15, 2016: Cancer Research
Eun Sook Jeong, Gabin Kim, Kyoung-Sik Moon, Yong-Bum Kim, Jung-Hwa Oh, Ho-Sook Kim, Jayoung Jeong, Jae-Gook Shin, Dong Hyun Kim
Colistin is a polypeptide antibiotic that effectively treats infections caused by multidrug-resistant Gram-negative bacteria, but its clinical use is limited due to nephrotoxicity. The purpose of the present study was to identify biomarkers of colistin-induced nephrotoxicity and to further characterize the mechanisms underlying this process by analyzing urinary metabolites using untargeted metabolomic approach. Rats receiving intraperitoneal administration of colistin sodium methanesulfonate (CMS) (25 or 50mg/kg) exhibited histopathological changes in the kidney and increased blood urea nitrogen levels...
April 25, 2016: Toxicology Letters
Aizhu Li, Xuejun Guo, Jiabin Xie, Xinyu Liu, Zhenzhu Zhang, Yubo Li, Yanjun Zhang
Corex Periplocae (the root of Periploca sepium Bge) has been widely used in clinics. Periplocin, as one of the components of cardiac glycosides in Corex Periplocae, easily triggers cardiotoxicity when used improperly. To evaluate the toxicity of Periplocin, we used UPLC-Q-TOF/MS to investigate metabolic profiles on neonatal rat cardiomyocytes exposed to high and low doses of Periplocin (0.2mmol/L, 0.4mmol/L). Finally, we identified 11 biomarkers associated with toxicity through multivariate statistical analysis...
May 10, 2016: Journal of Pharmaceutical and Biomedical Analysis
Miriam Hoene, Jia Li, Yanjie Li, Heike Runge, Xinjie Zhao, Hans-Ulrich Häring, Rainer Lehmann, Guowang Xu, Cora Weigert
Intracellular lipid pools are highly dynamic and tissue-specific. Physical exercise is a strong physiologic modulator of lipid metabolism, but most studies focus on changes induced by long-term training. To assess the acute effects of endurance exercise, mice were subjected to one hour of treadmill running, and (13)C16-palmitate was applied to trace fatty acid incorporation in soleus and gastrocnemius muscle and liver. The amounts of carnitine, FFA, lysophospholipids and diacylglycerol and the post-exercise increase in acetylcarnitine were pronouncedly higher in soleus than in gastrocnemius...
2016: Scientific Reports
Zhongkun Du, Yan Zhang, Guowei Wang, Jianbiao Peng, Zunyao Wang, Shixiang Gao
Triphenyl phosphate is a high production volume organophosphate flame retardant that has been detected in multiple environmental media at increasing concentrations. The environmental and health risks of triphenyl phosphate have drawn attention because of the multiplex toxicity of this chemical compound. However, few studies have paid close attention to the impacts of triphenyl phosphate on liver metabolism. We investigated hepatic histopathological, metabolomic and transcriptomic responses of zebrafish after exposure to 0...
2016: Scientific Reports
Nadine E Mascini, Menglin Cheng, Lu Jiang, Asif Rizwan, Helen Podmore, Dhaka R Bhandari, Andreas Römpp, Kristine Glunde, Ron M A Heeren
Although tumor hypoxia is associated with tumor aggressiveness and resistance to cancer treatment, many details of hypoxia-induced changes in tumors remain to be elucidated. Mass spectrometry imaging (MSI) is a technique that is well suited to study the biomolecular composition of specific tissue regions, such as hypoxic tumor regions. Here, we investigate the use of pimonidazole as an exogenous hypoxia marker for matrix-assisted laser desorption/ionization (MALDI) MSI. In hypoxic cells, pimonidazole is reduced and forms reactive products that bind to thiol groups in proteins, peptides, and amino acids...
March 15, 2016: Analytical Chemistry
Lucas Lindeboom, Yvonne M H Bruls, Petronella A van Ewijk, Matthijs K C Hesselink, Joachim E Wildberger, Patrick Schrauwen, Vera B Schrauwen-Hinderling
PURPOSE: Acetylcarnitine formation is suggested to be crucial in sustaining metabolic flexibility and glucose homeostasis. Recently, we introduced a method to detect acetylcarnitine in vivo with long TE (1) H-MRS. Differences in T1 relaxation time between lipids and acetylcarnitine can be exploited for additional lipid suppression in subjects with high myocellular lipid levels. METHODS: Acquisition of spectra with an inversion recovery sequence was alternated with standard signal acquisition to suppress short T1 metabolite signals...
February 17, 2016: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Rolf K Berge, Bodil Bjørndal, Elin Strand, Pavol Bohov, Carine Lindquist, Jan Erik Nordrehaug, Asbjørn Svardal, Jon Skorve, Ottar Nygård
BACKGROUND: Hepatic mitochondrial dysfunction plays an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Methyl donor supplementation has been shown to alleviate NAFLD, connecting the condition to the one-carbon metabolism. Thus, the objective was to investigate regulation of homocysteine (Hcy) and metabolites along the choline oxidation pathway during induction of hepatic steatosis by the fatty acid analogue tetradecylthiopropionic acid (TTP), an inhibitor of mitochondrial fatty acid oxidation...
2016: Lipids in Health and Disease
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