Specificity and rate of human and mouse liver and plasma phosphatidylcholine synthesis analyzed in vivo

Pynn, Christopher J.; Henderson, Neil; Clark, Howard; Koster, Grielof; Bernhard, Wolfgang; Postle, Anthony D.

doi:10.1194/jlr.d011916

Cited by 124 publications

(142 citation statements)

References 41 publications

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“…The unsaturated nature of normal liver PC composition is well-established (24), founded on PC synthesised via N-methylation of liver phosphatidylethanolamine (26) that supports the hepatic synthesis of VLDL (26). In control animals, as anticipated, we found the liver tissue PC molecular species composition is already a mostly unsaturated lipid pool consistent with previous work (24,26). The accumulated PC content that accompanies GM-CSF ablation resulted in a fractional super enrichment of PC16:0/18:2, PC16:0/22:6 and PC18:0/22:6 with an apparent fall in saturated and monunsaturated molecular species ( Figure 3A).…”

Section: Liverssupporting

confidence: 80%

“…Lipidomic analyses including calculations of absolute rates of lung tissue PC synthesis were undertaken as described (19,23,24).…”

Section: Methodsmentioning

confidence: 99%

“…Indeed, lung itself may be second only to the liver in the secretion of PUFA-rich lipoprotein into the circulation, albeit as HDL destined for liver recycling rather than VLDL. Liver amasses, through a mix of synthesis de novo via the N-methylation pathway (24) and salvage from lipoprotein remnants including HDL (32), PUFA-rich PC for VLDL construction prior to distribution via the circulation (32). More saturated hepatic PC species predominantly synthesised through the CDPcholine pathway (24) are segregated and preferentially secreted with the bile (40).…”

Section: Shg Microscopymentioning

confidence: 99%

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Hepatic Steatosis Accompanies Pulmonary Alveolar Proteinosis

Hunt

Malur

Monfort

et al. 2017

Am J Respir Cell Mol Biol

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Maintenance of tissue-specific organ lipid compositions characterises mammalian lipid homeostasis. Lung and liver synthesise mixed phosphatidylcholine (PC) molecular species subsequently "tailored" for function. Lungs progressively enrich disaturated PC (DSPC) directed to lamellar body (LB) surfactant stores prior to secretion. Liver accumulates polyunsaturated PC directed to VLDL assembly and secretion, or triglyceride stores. In each tissue, selective PC species enrichment mechanisms lie at the heart of effective homeostasis. We tested potential coordination between these spatially separated, but possibly complementary phenomena under a major derangement of lung PC metabolism, Pulmonary Alveolar Proteinosis (PAP), which overwhelms homeostasis leading to excessive surfactant accumulation. Using static and dynamic lipidomics techniques we compared (i) tissue PC compositions and contents and (ii) in lungs, the absolute rates of synthesis from both control mice and the GM-CSF knockout model of PAP. Significant DSPC accumulation in BALF, Alveolar Macrophage (AM) and lavaged lung tissue occurred alongside increased PC synthesis consistent with reported defects in AM surfactant turnover. However, microscopy using oil red O staining, CARS, SHG and TEM also revealed neutral lipid droplet accumulations in alveolar lipofibroblasts of GM-CSF KO animals suggesting lipid homeostasis deficits extend beyond AMs. PAP plasma PC composition was significantly PUFA-enriched but content was unchanged and hepatic PUFA-enriched PC content increased by 50% with an accompanying micro/macrovesicular steatosis and a fibrotic damage pattern consistent with NAFLD. These data suggest a hepato-pulmonary axis of PC metabolism coordination with wider implications for understanding and managing lipid pathologies where compromise of one organ has unexpected consequences for another.

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Section: Liverssupporting

confidence: 80%

“…Lipidomic analyses including calculations of absolute rates of lung tissue PC synthesis were undertaken as described (19,23,24).…”

Section: Methodsmentioning

confidence: 99%

Section: Shg Microscopymentioning

confidence: 99%

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Hepatic Steatosis Accompanies Pulmonary Alveolar Proteinosis

Hunt

Malur

Monfort

et al. 2017

Am J Respir Cell Mol Biol

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“…The discrepancy may be explained by the higher number of subjects in our study as well as differences in the regulation of PC production pathways. There are two different pathways for the formation of PCs with an enzyme specificity depending on the fatty acid species (Pynn et al, 2011).…”

Section: Correlations With Bfdmentioning

confidence: 99%

“…Phosphatidylcholine may be a source of fatty acids for triacylglycerols (van der Veen et al, 2012), which may explain why they often co-occur in the models. PC 32:0 was included in the model of VAT, whereas PC-O 36:5 and PC O-34:2 were included in the model of A:G ratio, possibly indicating tissue and fatty acid specific enzyme activity (Pynn et al, 2011;Raclot et al, 2001). For example, enzymes converting esterified fatty acids are known to vary between tissues (Kotronen et al, 2010).…”

Section: Added Value Of Metabolomics Analysismentioning

confidence: 99%

Gender-Dependent Associations of Metabolite Profiles and Body Fat Distribution in a Healthy Population with Central Obesity: Towards Metabolomics Diagnostics

Szymańska

Bouwman

Strassburg

et al. 2012

OMICS: A Journal of Integrative Biology

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Gender-dependent associations of metabolite profiles and body fat distribution in a healthy population with central obesity: towards metabolomics diagnostics Szymanska, E.; Bouwman, J.; Strassburg, K.; Vervoort, J.; Kangas, A.J.; Soininen, P.; AlaKorpela, M.; Westerhuis, J.A.; van Duynhoven, J.P.M.; Mela, D.J.; Macdonald, I.A.; Vreeken, R.J.; Smilde, A.K.; Jacobs, D.M. Published in: Omics DOI:10.1089/omi.2012.0062 Link to publication Citation for published version (APA):Szymaska, E., Bouwman, J., Strassburg, K., Vervoort, J., Kangas, A. J., Soininen, P., ... Jacobs, D. M. (2012). Gender-dependent associations of metabolite profiles and body fat distribution in a healthy population with central obesity: towards metabolomics diagnostics. Omics, 16(12), 652-667. DOI: 10.1089/omi.2012.0062 General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. AbstractObesity is a risk factor for cardiovascular diseases and type 2 diabetes especially when the fat is accumulated to central depots. Novel biomarkers are crucial to develop diagnostics for obesity and related metabolic disorders. We evaluated the associations between metabolite profiles (136 lipid components, 12 lipoprotein subclasses, 17 low-molecular-weight metabolites, 12 clinical markers) and 28 phenotype parameters (including different body fat distribution parameters such as android (A), gynoid (G), abdominal visceral (VAT), subcutaneous (SAT) fat) in 215 plasma/serum samples from healthy overweight men (n = 32) and women (n = 83) with central obesity.(Partial) correlation analysis and partial least squares (PLS) regression analysis showed that only specific metabolites were associated to A:G ratio, VAT, and SAT, respectively. These association patterns were gender dependent. For example, insulin, cholesterol, VLDL, and certain triacylglycerols (TG 54:1-3) correlated to VAT in women, while in men VAT was associated with TG 50:1-5, TG 55:1, phosphatidylcholine (PC 32:0), and VLDL ((X)L). Moreover, multiple regression analysis revealed that waist circumference and total fat were sufficient to predict VAT and SAT in women. In contrast, only VAT but not SAT could be predicted in men and only when plasma metabolites were included, with PC 32:0 being most strongly associated with VAT. These findings collectively highlight the p...

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Lipidomics Perspective: From Molecular Lipidomics to Validated Clinical Diagnostics

Ekroos

2012

Lipidomics

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Specificity and rate of human and mouse liver and plasma phosphatidylcholine synthesis analyzed in vivo

Cited by 124 publications

References 41 publications

Hepatic Steatosis Accompanies Pulmonary Alveolar Proteinosis

Hepatic Steatosis Accompanies Pulmonary Alveolar Proteinosis

Gender-Dependent Associations of Metabolite Profiles and Body Fat Distribution in a Healthy Population with Central Obesity: Towards Metabolomics Diagnostics

Lipidomics Perspective: From Molecular Lipidomics to Validated Clinical Diagnostics

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