Carnitine, acylcarnitine and amino acid profiles analyzed by tandem mass spectrometry in a surfactant/virus mouse model of acute hepatic encephalopathy

ObjectivesTo identify metabolic markers that can classify patients with osteoarthritis (OA) into subgroups.DesignA case-only study design was utilised.ParticipantsPatients were recruited from those who underwent total knee or hip replacement surgery due to primary OA between November 2011 and December 2013 in St. Clare's Mercy Hospital and Health Science Centre General Hospital in St. John's, capital of Newfoundland and Labrador (NL), Canada. 38 men and 42 women were included in the study. The mean age was 65.2±8.7 years.Outcome measuresSynovial fluid samples were collected at the time of their joint surgeries. Metabolic profiling was performed on the synovial fluid samples by the targeted metabolomics approach, and various analytic methods were utilised to identify metabolic markers for classifying subgroups of patients with OA. Potential confounders such as age, sex, body mass index (BMI) and comorbidities were considered in the analysis.ResultsTwo distinct patient groups, A and B, were clearly identified in the 80 patients with OA. Patients in group A had a significantly higher concentration on 37 of 39 acylcarnitines, but the free carnitine was significantly lower in their synovial fluids than in those of patients in group B. The latter group was further subdivided into two subgroups, that is, B1 and B2. The corresponding metabolites that contributed to the grouping were 86 metabolites including 75 glycerophospholipids (6 lysophosphatidylcholines, 69 phosphatidylcholines), 9 sphingolipids, 1 biogenic amine and 1 acylcarnitine. The grouping was not associated with any known confounders including age, sex, BMI and comorbidities. The possible biological processes involved in these clusters are carnitine, lipid and collagen metabolism, respectively.ConclusionsThe study demonstrated that OA consists of metabolically distinct subgroups. Identification of these distinct subgroups will help to unravel the pathogenesis and develop targeted therapies for OA.

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“…Elevated acylcarnitine levels have been detected in obesity, 22 type-2 diabetes, 23 cardiovascular disease 24 and encephalopathy. 25 …”

Section: Discussionmentioning

confidence: 99%

Classification of osteoarthritis phenotypes by metabolomics analysis

et al. 2014

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“…During the past decade we have investigated the effects of Tox exposure on fat and carbohydrate metabolism in neonatal mouse livers as part of our long-term study of Tox potentiation of influenza B-induced mortality [2,4]. Mice exposed dermally to Tox daily for 12 consecutive days exhibit significant stimulation of peroxisomal fatty-acid β-oxidation (FAO) [5] and inhibition of mitochondrial FAO [6], elevated synthesis of fatty acylcarnitines [7] and significant reductions in glycogen content [2]. In spite of these metabolic disturbances, the young mice have no apparent adverse health effects from Tox exposure.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

The pesticide adjuvant, Toximul™, alters hepatic metabolism through effects on downstream targets of PPARα

Upham

Acott²,

O’Regan³

et al. 2007

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Previous studies demonstrated that chronic dermal exposure to the pesticide adjuvant (surfactant), Toximul (Tox), has significant detrimental effects on hepatic lipid metabolism. This study demonstrated that young mice dermally exposed to Tox for 12 days have significant increases in expression of peroxisomal acyl-CoA oxidase (mRNA and protein), bifunctional enzyme (mRNA) and thiolase (mRNA), as well as the P450 oxidizing enzymes Cyp4A10 and Cyp4A14 (mRNA and protein). Tox produced a similar pattern of increases in wild type adult female mice but did not induce these responses in PPARalpha-null mice. These data support the hypothesis that Tox, a heterogeneous blend of nonionic and anionic surfactants, modulates hepatic metabolism at least in part through activation of PPARalpha. Notably, all three groups of Tox-treated mice had increased relative liver weights due to significant accumulation of lipid. This could be endogenous in nature and/or a component(s) of Tox or a metabolite thereof. The ability of Tox and other hydrocarbon pollutants to induce fatty liver despite being PPARalpha agonists indicates a novel consequence of exposure to this class of chemicals, and may provide a new understanding of fatty liver in populations with industrial exposure.

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Current literature in mass spectrometry

2008

J. Mass Spectrom.

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In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of mass spectrometry. Each bibliography is divided into 11 sections: 1 Reviews; 2 Instrumental Techniques & Methods; 3 Gas Phase Ion Chemistry; 4 Biology/Biochemistry: Amino Acids, Peptides & Proteins; Carbohydrates; Lipids; Nucleic Acids; 5 Pharmacology/Toxicology; 6 Natural Products; 7 Analysis of Organic Compounds; 8 Analysis of Inorganics/Organometallics; 9 Surface Analysis; 10 Environmental Analysis; 11 Elemental Analysis. Within each section, articles are listed in alphabetical order with respect to author (6 Weeks journals ‐ Search completed at 5th. Dec. 2007)

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Carnitine, acylcarnitine and amino acid profiles analyzed by tandem mass spectrometry in a surfactant/virus mouse model of acute hepatic encephalopathy

Cited by 7 publications

References 28 publications

Classification of osteoarthritis phenotypes by metabolomics analysis

Classification of osteoarthritis phenotypes by metabolomics analysis

The pesticide adjuvant, Toximul™, alters hepatic metabolism through effects on downstream targets of PPARα

Current literature in mass spectrometry

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