These authors contributed equally.
Steatohepatitis/Metabolic Liver Disease
Excess S-adenosylmethionine reroutes phosphatidylethanolamine towards phosphatidylcholine and triglyceride synthesis
Article first published online: 14 AUG 2013
Copyright © 2013 by the American Association for the Study of Liver Diseases
Volume 58, Issue 4, pages 1296–1305, October 2013
How to Cite
Martínez-Uña, M., Varela-Rey, M., Cano, A., Fernández-Ares, L., Beraza, N., Aurrekoetxea, I., Martínez-Arranz, I., García-Rodríguez, J. L., Buqué, X., Mestre, D., Luka, Z., Wagner, C., Alonso, C., Finnell, R. H., Lu, S. C., Martínez-Chantar, M. L., Aspichueta, P. and Mato, J. M. (2013), Excess S-adenosylmethionine reroutes phosphatidylethanolamine towards phosphatidylcholine and triglyceride synthesis. Hepatology, 58: 1296–1305. doi: 10.1002/hep.26399
See Editorial on Page 1207
Potential conflict of interest: Nothing to report.
Supported by NIH RO1AT1576, RO1AT004896 (M.L.M-C., S.C.L., J.M.M.), RO1DK051719 (S.C.L., J.M.M.), R01DK080010, R01DK15289 (C.W.), Spanish Plan Nacional I+D SAF 2011-29851 (J.M.M.), ETORTEK-2010 Gobierno Vasco (P.A., M.L.M.-C, J.M.M.), PI11/01588, Sanidad Gobierno Vasco 2008, Educación Gobierno Vasco 2011 (M.L.M.-C), 2012 (J.M.M.), Sanidad Gobierno Vasco 2012 (M.V.R.), Basque Goverment IT-336-10 (to P.A. and X.B.), Saiotek S-PE11UN033 (P.A.), BBVA Foundation (to J.M.M., R.H.F.). Ciberehd is funded by ISCiii.
- Issue published online: 1 OCT 2013
- Article first published online: 14 AUG 2013
- Accepted manuscript online: 16 MAR 2013 02:17AM EST
- Manuscript Accepted: 10 MAR 2013
- Manuscript Received: 16 NOV 2012
Additional Supporting Information may be found in the online version of this article.
|hep26399-sup-0001-suppfig1.tif||4790K||Supporting Figure 1. Metabolic context in Gnmt-/- mice. 3-month-old wild type (WT) and Gnmt-/- (KO) mice were fasted 3 hours before experiments were performed. (a) Glucose and insulin tolerance tests were assayed after oral administration of glucose (2mg/kg) or intraperitoneal injection of insulin (1U/kg). (b) Serum fatty acid (FA) concentrations. (c) Food intake. (d) Body weight. (e) Percentage of liver weight (f). Percentage of white adipose tissue (WAT). Values are mean±SEM of 4 animals per group. Statistical differences between Gnmt-/- and WT mice are denoted by **p<0.01; ***p<0.001 (Student's t test) and by two-way ANOVA.|
|hep26399-sup-0002-suppfig2.tif||5429K||Supporting Figure 2. Gnmt ablation increases phosphatidylcholine content in serum HDL fractions. 3-month-old wild type (WT) and Gnmt-/- (KO) mice were fasted 2 hours before experiments were performed. (a) Phosphatidylcholine content in serum lipoprotein fractions was quantified by a commercially available kit (Spinreact, Spain). Lipoprotein fractions were separated by AKTA fast-protein liquid chromatography using a Superose 6TM 10/300 column (GE Healthcare, Sweden). (b) Representative hematoxylin and eosin staining from 3-month-old wild type (WT), Gnmt-/- (KO) and MDD-treated Gnmt-/-(KO-MDD) mice. Values are mean±SEM of 4 animals per group. Statistical differences between Gnmt-/- and WT mice are denoted by *p<0.05; **p<0.01; ***p<0.001 (Student's t test).|
|hep26399-sup-0003-suppfig3.tif||4790K||Supporting Figure 3. Gnmt ablation increases hepatic flux from PE to PC in 8 month-old Gnmt-/- mice. 8-month-old wild type (WT) and Gnmt-/- (KO) mice were fasted 2 hours before experiments were performed. (a) Hepatocytes were isolated and incubated with [3H]ethanolamine for 4 hours, and the radioactivity incorporated into PC was expressed as a percentage of the radiolabel incorporated into PC plus PE. Microsomes were isolated from WT and Gnmt-/- mice liver, and PE and PC levels quantified after lipid extraction and separation by TLC. (b) Liver PE and PC were quantified as mentioned before and liver PC/PE ratio was calculated. (c) Liver DG and (d) TG were quantified as mentioned before. (e) Hepatic TG secretion rate was measured after inhibition of VLDL metabolism with 1 g/kg poloxamer (P-407). Values are mean±SEM of 4 animals per group. Statistical differences between Gnmt-/- and WT mice are denoted by *p<0.05; **p<0.01; ***p<0.001 (Student's t test).|
|hep26399-sup-0004-supptab1.doc||314K||Table 1 Supporting Lipidomic analysis of livers from Gnmt -/-, Gnmt -/--MDD, and Gnmt -/-Plin2 -/- mice|
|hep26399-sup-0005-supptab2.doc||179K||Table 2 Supporting Sequences of the primers used|
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