Stable Isotopic Tracer Phospholipidomics Reveals Contributions of Key Phospholipid Biosynthetic Pathways to Low Hepatocyte Phosphatidylcholine to Phosphatidylethanolamine Ratio Induced by Free Fatty Acids
There is a strong association between hepatocyte phospholipid homeostasis and non-alcoholic fatty liver disease (NAFLD). The phosphatidylcholine to phosphatidylethanolamine ratio (PC/PE) often draws special attention as genetic and dietary disruptions to this ratio can provoke steatohepatitis and ot...
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| Published in | Metabolites Vol. 11; no. 3; p. 188 |
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| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
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22.03.2021
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| Abstract | There is a strong association between hepatocyte phospholipid homeostasis and non-alcoholic fatty liver disease (NAFLD). The phosphatidylcholine to phosphatidylethanolamine ratio (PC/PE) often draws special attention as genetic and dietary disruptions to this ratio can provoke steatohepatitis and other signs of NAFLD. Here we demonstrated that excessive free fatty acid (1:2 mixture of palmitic and oleic acid) alone was able to significantly lower the phosphatidylcholine to phosphatidylethanolamine ratio, along with substantial alterations to phospholipid composition in rat hepatocytes. This involved both a decrease in hepatocyte phosphatidylcholine (less prominent) and an increase in phosphatidylethanolamine, with the latter contributing more to the lowered ratio. Stable isotopic tracer phospholipidomic analysis revealed several previously unidentified changes that were triggered by excessive free fatty acid. Importantly, the enhanced cytidine diphosphate (CDP)-ethanolamine pathway activity appeared to be driven by the increased supply of preferred fatty acid substrates. By contrast, the phosphatidylethanolamine N-methyl transferase (PEMT) pathway was restricted by low endogenous methionine and consequently low S-adenosylmethionine, which resulted in a concomitant decrease in phosphatidylcholine and accumulation of phosphatidylethanolamine. Overall, our study identified several previously unreported links in the relationship between hepatocyte free fatty acid overload, phospholipid homeostasis, and the development of NAFLD. |
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| AbstractList | There is a strong association between hepatocyte phospholipid homeostasis and non-alcoholic fatty liver disease (NAFLD). The phosphatidylcholine to phosphatidylethanolamine ratio (PC/PE) often draws special attention as genetic and dietary disruptions to this ratio can provoke steatohepatitis and other signs of NAFLD. Here we demonstrated that excessive free fatty acid (1:2 mixture of palmitic and oleic acid) alone was able to significantly lower the phosphatidylcholine to phosphatidylethanolamine ratio, along with substantial alterations to phospholipid composition in rat hepatocytes. This involved both a decrease in hepatocyte phosphatidylcholine (less prominent) and an increase in phosphatidylethanolamine, with the latter contributing more to the lowered ratio. Stable isotopic tracer phospholipidomic analysis revealed several previously unidentified changes that were triggered by excessive free fatty acid. Importantly, the enhanced cytidine diphosphate (CDP)-ethanolamine pathway activity appeared to be driven by the increased supply of preferred fatty acid substrates. By contrast, the phosphatidylethanolamine N-methyl transferase (PEMT) pathway was restricted by low endogenous methionine and consequently low S-adenosylmethionine, which resulted in a concomitant decrease in phosphatidylcholine and accumulation of phosphatidylethanolamine. Overall, our study identified several previously unreported links in the relationship between hepatocyte free fatty acid overload, phospholipid homeostasis, and the development of NAFLD. There is a strong association between hepatocyte phospholipid homeostasis and non-alcoholic fatty liver disease (NAFLD). The phosphatidylcholine to phosphatidylethanolamine ratio (PC/PE) often draws special attention as genetic and dietary disruptions to this ratio can provoke steatohepatitis and other signs of NAFLD. Here we demonstrated that excessive free fatty acid (1:2 mixture of palmitic and oleic acid) alone was able to significantly lower the phosphatidylcholine to phosphatidylethanolamine ratio, along with substantial alterations to phospholipid composition in rat hepatocytes. This involved both a decrease in hepatocyte phosphatidylcholine (less prominent) and an increase in phosphatidylethanolamine, with the latter contributing more to the lowered ratio. Stable isotopic tracer phospholipidomic analysis revealed several previously unidentified changes that were triggered by excessive free fatty acid. Importantly, the enhanced cytidine diphosphate (CDP)-ethanolamine pathway activity appeared to be driven by the increased supply of preferred fatty acid substrates. By contrast, the phosphatidylethanolamine N -methyl transferase (PEMT) pathway was restricted by low endogenous methionine and consequently low S -adenosylmethionine, which resulted in a concomitant decrease in phosphatidylcholine and accumulation of phosphatidylethanolamine. Overall, our study identified several previously unreported links in the relationship between hepatocyte free fatty acid overload, phospholipid homeostasis, and the development of NAFLD. There is a strong association between hepatocyte phospholipid homeostasis and non-alcoholic fatty liver disease (NAFLD). The phosphatidylcholine to phosphatidylethanolamine ratio (PC/PE) often draws special attention as genetic and dietary disruptions to this ratio can provoke steatohepatitis and other signs of NAFLD. Here we demonstrated that excessive free fatty acid (1:2 mixture of palmitic and oleic acid) alone was able to significantly lower the phosphatidylcholine to phosphatidylethanolamine ratio, along with substantial alterations to phospholipid composition in rat hepatocytes. This involved both a decrease in hepatocyte phosphatidylcholine (less prominent) and an increase in phosphatidylethanolamine, with the latter contributing more to the lowered ratio. Stable isotopic tracer phospholipidomic analysis revealed several previously unidentified changes that were triggered by excessive free fatty acid. Importantly, the enhanced cytidine diphosphate (CDP)-ethanolamine pathway activity appeared to be driven by the increased supply of preferred fatty acid substrates. By contrast, the phosphatidylethanolamine -methyl transferase (PEMT) pathway was restricted by low endogenous methionine and consequently low -adenosylmethionine, which resulted in a concomitant decrease in phosphatidylcholine and accumulation of phosphatidylethanolamine. Overall, our study identified several previously unreported links in the relationship between hepatocyte free fatty acid overload, phospholipid homeostasis, and the development of NAFLD. There is a strong association between hepatocyte phospholipid homeostasis and non-alcoholic fatty liver disease (NAFLD). The phosphatidylcholine to phosphatidylethanolamine ratio (PC/PE) often draws special attention as genetic and dietary disruptions to this ratio can provoke steatohepatitis and other signs of NAFLD. Here we demonstrated that excessive free fatty acid (1:2 mixture of palmitic and oleic acid) alone was able to significantly lower the phosphatidylcholine to phosphatidylethanolamine ratio, along with substantial alterations to phospholipid composition in rat hepatocytes. This involved both a decrease in hepatocyte phosphatidylcholine (less prominent) and an increase in phosphatidylethanolamine, with the latter contributing more to the lowered ratio. Stable isotopic tracer phospholipidomic analysis revealed several previously unidentified changes that were triggered by excessive free fatty acid. Importantly, the enhanced cytidine diphosphate (CDP)-ethanolamine pathway activity appeared to be driven by the increased supply of preferred fatty acid substrates. By contrast, the phosphatidylethanolamine N-methyl transferase (PEMT) pathway was restricted by low endogenous methionine and consequently low S-adenosylmethionine, which resulted in a concomitant decrease in phosphatidylcholine and accumulation of phosphatidylethanolamine. Overall, our study identified several previously unreported links in the relationship between hepatocyte free fatty acid overload, phospholipid homeostasis, and the development of NAFLD.There is a strong association between hepatocyte phospholipid homeostasis and non-alcoholic fatty liver disease (NAFLD). The phosphatidylcholine to phosphatidylethanolamine ratio (PC/PE) often draws special attention as genetic and dietary disruptions to this ratio can provoke steatohepatitis and other signs of NAFLD. Here we demonstrated that excessive free fatty acid (1:2 mixture of palmitic and oleic acid) alone was able to significantly lower the phosphatidylcholine to phosphatidylethanolamine ratio, along with substantial alterations to phospholipid composition in rat hepatocytes. This involved both a decrease in hepatocyte phosphatidylcholine (less prominent) and an increase in phosphatidylethanolamine, with the latter contributing more to the lowered ratio. Stable isotopic tracer phospholipidomic analysis revealed several previously unidentified changes that were triggered by excessive free fatty acid. Importantly, the enhanced cytidine diphosphate (CDP)-ethanolamine pathway activity appeared to be driven by the increased supply of preferred fatty acid substrates. By contrast, the phosphatidylethanolamine N-methyl transferase (PEMT) pathway was restricted by low endogenous methionine and consequently low S-adenosylmethionine, which resulted in a concomitant decrease in phosphatidylcholine and accumulation of phosphatidylethanolamine. Overall, our study identified several previously unreported links in the relationship between hepatocyte free fatty acid overload, phospholipid homeostasis, and the development of NAFLD. |
| Author | Peng, Kang-Yu Murphy, Andrew J Barlow, Christopher K Weir, Jacquelyn M Meikle, Peter J Febbraio, Mark A Kammoun, Helene Mellett, Natalie A |
| AuthorAffiliation | 2 Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC 3010, Australia 4 Hematopoiesis & Leukocyte Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia; helene.kammoun@mcri.edu.au (H.K.); Andrew.Murphy@baker.edu.au (A.J.M.) 1 Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia; Kang-Yu.Peng@hri.org.au (K.-Y.P.); chris.barlow@monash.edu (C.K.B.); Natalie.Mellett@baker.edu.au (N.A.M.); jacquio77@gmail.com (J.M.W.) 3 Proteomics and Metabolomics Facility and the Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia 6 Baker Department of Cardiometabolic Health, University of Melbourne, Parkville, VIC 3010, Australia 5 Cellular & Molecular Metabolism Laboratory, Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, Australia; mark.febbraio@monash.edu |
| AuthorAffiliation_xml | – name: 5 Cellular & Molecular Metabolism Laboratory, Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, Australia; mark.febbraio@monash.edu – name: 4 Hematopoiesis & Leukocyte Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia; helene.kammoun@mcri.edu.au (H.K.); Andrew.Murphy@baker.edu.au (A.J.M.) – name: 2 Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC 3010, Australia – name: 6 Baker Department of Cardiometabolic Health, University of Melbourne, Parkville, VIC 3010, Australia – name: 1 Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia; Kang-Yu.Peng@hri.org.au (K.-Y.P.); chris.barlow@monash.edu (C.K.B.); Natalie.Mellett@baker.edu.au (N.A.M.); jacquio77@gmail.com (J.M.W.) – name: 3 Proteomics and Metabolomics Facility and the Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia |
| Author_xml | – sequence: 1 givenname: Kang-Yu orcidid: 0000-0003-4024-4088 surname: Peng fullname: Peng, Kang-Yu – sequence: 2 givenname: Christopher K surname: Barlow fullname: Barlow, Christopher K – sequence: 3 givenname: Helene surname: Kammoun fullname: Kammoun, Helene – sequence: 4 givenname: Natalie A surname: Mellett fullname: Mellett, Natalie A – sequence: 5 givenname: Jacquelyn M surname: Weir fullname: Weir, Jacquelyn M – sequence: 6 givenname: Andrew J surname: Murphy fullname: Murphy, Andrew J – sequence: 7 givenname: Mark A surname: Febbraio fullname: Febbraio, Mark A – sequence: 8 givenname: Peter J orcidid: 0000-0002-2593-4665 surname: Meikle fullname: Meikle, Peter J |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33809964$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1016_j_bbalip_2024_159514 crossref_primary_10_5606_tftrd_2024_15287 crossref_primary_10_3389_fmicb_2023_1145430 crossref_primary_10_1016_j_cca_2022_12_014 |
| Cites_doi | 10.1016/j.bbalip.2012.08.016 10.1194/jlr.P035808 10.1194/jlr.M085613 10.1016/j.copbio.2012.10.015 10.1042/CS20110060 10.1016/j.chembiol.2018.10.008 10.1074/jbc.274.42.29683 10.3945/ajcn.113.066092 10.1152/ajpgi.2000.279.1.G178 10.1111/j.1530-0277.1997.tb04259.x 10.1073/pnas.091016398 10.1074/jbc.M703786200 10.1016/S0021-9258(19)42333-8 10.1002/hep.24607 10.1073/pnas.96.22.12737 10.1042/BST20140138 10.1016/S0022-2275(20)42084-X 10.1210/en.2005-1494 10.1016/j.cmet.2006.03.007 10.1074/jbc.M108911200 10.1002/hep.22239 10.1016/S1665-2681(19)31355-9 10.1194/jlr.D011916 10.2337/db11-0425 10.1146/annurev.nutr.28.061807.155438 10.1016/0005-2760(84)90203-0 10.1016/S0021-9258(19)41523-8 10.1016/S1043-2760(00)00323-4 10.1172/JCI115534 10.1038/nature09968 10.1016/j.tem.2017.11.009 10.1016/S0016-5085(98)70599-2 10.1016/j.dld.2012.09.002 10.1016/j.molmet.2014.04.010 10.1038/srep46658 10.1016/j.cbi.2006.11.004 10.1016/j.cmet.2013.07.004 10.1161/ATVBAHA.111.234096 10.1371/annotation/9dd8c2df-1921-45b4-b3ba-8919f9068aea 10.1139/o03-073 10.1074/jbc.M109.099333 10.1002/hep.20283 10.1016/j.copbio.2010.01.011 |
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| Keywords | CDP-choline pathway flux analysis phosphatidylethanolamine N-methyl transferase (PEMT) pathway free fatty acid CDP-ethanolamine pathway steatosis lipidomics |
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| References | Sundler (ref_22) 1974; 249 Bergman (ref_26) 2000; 11 Vance (ref_1) 2004; 82 Feldstein (ref_19) 2004; 40 Barak (ref_28) 1997; 21 DeLong (ref_15) 2002; 277 Mueller (ref_13) 2013; 24 ref_31 Li (ref_4) 2006; 3 Kalhan (ref_34) 2011; 121 Cano (ref_3) 2014; 42 Mato (ref_24) 2013; 12 Svedberg (ref_27) 1991; 88 Karpe (ref_25) 2011; 60 Lu (ref_37) 2001; 98 Weir (ref_41) 2013; 54 Chiappini (ref_7) 2017; 7 Pynn (ref_16) 2011; 52 Lu (ref_29) 2000; 279 DeLong (ref_14) 1999; 274 Donato (ref_20) 2007; 165 Niklas (ref_12) 2010; 21 Homan (ref_23) 1991; 32 Dahlhoff (ref_32) 2014; 3 Vance (ref_2) 2013; 1831 Mas (ref_5) 2013; 45 Sundler (ref_10) 1975; 250 Bleijerveld (ref_17) 2007; 282 Wu (ref_21) 2008; 47 Day (ref_33) 1998; 114 Fu (ref_8) 2011; 473 Audubert (ref_11) 1984; 792 Palomer (ref_9) 2018; 29 Caballero (ref_6) 2010; 285 Karaskov (ref_39) 2006; 147 Meikle (ref_40) 2011; 31 Peng (ref_42) 2018; 59 Mato (ref_36) 2008; 28 Ahrens (ref_35) 2013; 18 Cano (ref_30) 2011; 54 Yan (ref_18) 2013; 98 Foretz (ref_38) 1999; 96 Huynh (ref_43) 2019; 26 |
| References_xml | – volume: 1831 start-page: 543 year: 2013 ident: ref_2 article-title: Formation and Function of Phosphatidylserine and Phosphatidylethanolamine in Mammalian Cells publication-title: Biochim. Biophys. Acta doi: 10.1016/j.bbalip.2012.08.016 – volume: 54 start-page: 2898 year: 2013 ident: ref_41 article-title: Plasma Lipid Profiling in a Large Population-Based Cohort publication-title: J. Lipid Res. doi: 10.1194/jlr.P035808 – volume: 59 start-page: 1977 year: 2018 ident: ref_42 article-title: Mitochondrial Dysfunction-Related Lipid Changes Occur in Nonalcoholic Fatty Liver Disease Progression publication-title: J. Lipid Res. doi: 10.1194/jlr.M085613 – volume: 24 start-page: 54 year: 2013 ident: ref_13 article-title: Stable Isotope-Assisted Metabolomics to Detect Metabolic Flux Changes in Mammalian Cell Cultures publication-title: Curr. Opin. Biotechnol. doi: 10.1016/j.copbio.2012.10.015 – volume: 121 start-page: 179 year: 2011 ident: ref_34 article-title: Methionine and Protein Metabolism in Non-Alcoholic Steatohepatitis: Evidence for Lower Rate of Transmethylation of Methionine publication-title: Clin. Sci. doi: 10.1042/CS20110060 – volume: 26 start-page: 71 year: 2019 ident: ref_43 article-title: High-Throughput Plasma Lipidomics: Detailed Mapping of the Associations with Cardiometabolic Risk Factors publication-title: Cell Chem. Biol. doi: 10.1016/j.chembiol.2018.10.008 – volume: 274 start-page: 29683 year: 1999 ident: ref_14 article-title: Molecular Distinction of Phosphatidylcholine Synthesis between the CDP-Choline Pathway and Phosphatidylethanolamine Methylation Pathway publication-title: J. Biol. Chem. doi: 10.1074/jbc.274.42.29683 – volume: 98 start-page: 1459 year: 2013 ident: ref_18 article-title: Pregnancy Alters Choline Dynamics: Results of a Randomized Trial Using Stable Isotope Methodology in Pregnant and Nonpregnant Women publication-title: Am. J. Clin. Nutr. doi: 10.3945/ajcn.113.066092 – volume: 279 start-page: G178 year: 2000 ident: ref_29 article-title: Changes in Methionine Adenosyltransferase and S-Adenosylmethionine Homeostasis in Alcoholic Rat Liver publication-title: Am. J. Physiol. Gastrointest. Liver Physiol. doi: 10.1152/ajpgi.2000.279.1.G178 – volume: 21 start-page: 1100 year: 1997 ident: ref_28 article-title: The Effect of Betaine in Reversing Alcoholic Steatosis publication-title: Alcohol. Clin. Exp. Res. doi: 10.1111/j.1530-0277.1997.tb04259.x – volume: 98 start-page: 5560 year: 2001 ident: ref_37 article-title: Methionine Adenosyltransferase 1A Knockout Mice Are Predisposed to Liver Injury and Exhibit Increased Expression of Genes Involved in Proliferation publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.091016398 – volume: 282 start-page: 28362 year: 2007 ident: ref_17 article-title: The CDP-Ethanolamine Pathway and Phosphatidylserine Decarboxylation Generate Different Phosphatidylethanolamine Molecular Species publication-title: J. Biol. Chem. doi: 10.1074/jbc.M703786200 – volume: 249 start-page: 5102 year: 1974 ident: ref_22 article-title: Effect of Different Fatty Acids on Glycerolipid Synthesis in Isolated Rat Hepatocytes publication-title: J. Biol. Chem. doi: 10.1016/S0021-9258(19)42333-8 – volume: 54 start-page: 1975 year: 2011 ident: ref_30 article-title: Methionine Adenosyltransferase 1A Gene Deletion Disrupts Hepatic Very Low-Density Lipoprotein Assembly in Mice publication-title: Hepatology doi: 10.1002/hep.24607 – volume: 96 start-page: 12737 year: 1999 ident: ref_38 article-title: Sterol Regulatory Element Binding Protein-1c Is a Major Mediator of Insulin Action on the Hepatic Expression of Glucokinase and Lipogenesis-Related Genes publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.96.22.12737 – volume: 42 start-page: 1447 year: 2014 ident: ref_3 article-title: Deciphering Non-Alcoholic Fatty Liver Disease through Metabolomics: Figure 1 publication-title: Biochem. Soc. Trans. doi: 10.1042/BST20140138 – volume: 32 start-page: 231 year: 1991 ident: ref_23 article-title: Differential Effects of Eicosapentaenoic Acid and Oleic Acid on Lipid Synthesis and Secretion by HepG2 Cells publication-title: J. Lipid Res. doi: 10.1016/S0022-2275(20)42084-X – volume: 147 start-page: 3398 year: 2006 ident: ref_39 article-title: Chronic Palmitate but Not Oleate Exposure Induces Endoplasmic Reticulum Stress, Which May Contribute to INS-1 Pancreatic Beta-Cell Apoptosis publication-title: Endocrinology doi: 10.1210/en.2005-1494 – volume: 3 start-page: 321 year: 2006 ident: ref_4 article-title: The Ratio of Phosphatidylcholine to Phosphatidylethanolamine Influences Membrane Integrity and Steatohepatitis publication-title: Cell Metab. doi: 10.1016/j.cmet.2006.03.007 – volume: 277 start-page: 17217 year: 2002 ident: ref_15 article-title: Disruption of Choline Methyl Group Donation for Phosphatidylethanolamine Methylation in Hepatocarcinoma Cells publication-title: J. Biol. Chem. doi: 10.1074/jbc.M108911200 – volume: 47 start-page: 1905 year: 2008 ident: ref_21 article-title: Prevention of Free Fatty Acid-Induced Hepatic Lipotoxicity by 18beta-Glycyrrhetinic Acid through Lysosomal and Mitochondrial Pathways publication-title: Hepatology doi: 10.1002/hep.22239 – volume: 12 start-page: 183 year: 2013 ident: ref_24 article-title: S-Adenosylmethionine Metabolism and Liver Disease publication-title: Ann. Hepatol. doi: 10.1016/S1665-2681(19)31355-9 – volume: 52 start-page: 399 year: 2011 ident: ref_16 article-title: Specificity and Rate of Human and Mouse Liver and Plasma Phosphatidylcholine Synthesis Analyzed in Vivo publication-title: J. Lipid Res. doi: 10.1194/jlr.D011916 – volume: 60 start-page: 2441 year: 2011 ident: ref_25 article-title: Fatty Acids, Obesity, and Insulin Resistance: Time for a Reevaluation publication-title: Diabetes doi: 10.2337/db11-0425 – volume: 28 start-page: 273 year: 2008 ident: ref_36 article-title: Methionine Metabolism and Liver Disease publication-title: Annu. Rev. Nutr. doi: 10.1146/annurev.nutr.28.061807.155438 – volume: 792 start-page: 348 year: 1984 ident: ref_11 article-title: Fatty Acids Inhibit N-Methylation of Phosphatidylethanolamine in Rat Hepatocytes and Liver Microsomes publication-title: Biochim. Biophys. Acta doi: 10.1016/0005-2760(84)90203-0 – volume: 250 start-page: 3359 year: 1975 ident: ref_10 article-title: Regulation of Phospholipid Biosynthesis in Isolated Rat Hepatocytes. Effect of Different Substrates publication-title: J. Biol. Chem. doi: 10.1016/S0021-9258(19)41523-8 – volume: 11 start-page: 351 year: 2000 ident: ref_26 article-title: Free Fatty Acids and Pathogenesis of Type 2 Diabetes Mellitus publication-title: Trends Endocrinol. Metab. doi: 10.1016/S1043-2760(00)00323-4 – volume: 88 start-page: 2054 year: 1991 ident: ref_27 article-title: Fatty Acids in the Portal Vein of the Rat Regulate Hepatic Insulin Clearance publication-title: J. Clin. Investig. doi: 10.1172/JCI115534 – volume: 473 start-page: 528 year: 2011 ident: ref_8 article-title: Aberrant Lipid Metabolism Disrupts Calcium Homeostasis Causing Liver Endoplasmic Reticulum Stress in Obesity publication-title: Nature doi: 10.1038/nature09968 – volume: 29 start-page: 178 year: 2018 ident: ref_9 article-title: Palmitic and Oleic Acid: The Yin and Yang of Fatty Acids in Type 2 Diabetes Mellitus publication-title: Trends Endocrinol. Metab. doi: 10.1016/j.tem.2017.11.009 – volume: 114 start-page: 842 year: 1998 ident: ref_33 article-title: Steatohepatitis: A Tale of Two “Hits”? publication-title: Gastroenterology doi: 10.1016/S0016-5085(98)70599-2 – volume: 45 start-page: 147 year: 2013 ident: ref_5 article-title: The Pro-Inflammatory Action of Tumour Necrosis Factor-α in Non-Alcoholic Steatohepatitis Is Independent of the NSMAF Gene Product publication-title: Dig. Liver Dis. doi: 10.1016/j.dld.2012.09.002 – volume: 3 start-page: 565 year: 2014 ident: ref_32 article-title: Methyl-Donor Supplementation in Obese Mice Prevents the Progression of NAFLD, Activates AMPK and Decreases Acyl-Carnitine Levels publication-title: Mol. Metab. doi: 10.1016/j.molmet.2014.04.010 – volume: 7 start-page: 46658 year: 2017 ident: ref_7 article-title: Metabolism Dysregulation Induces a Specific Lipid Signature of Nonalcoholic Steatohepatitis in Patients publication-title: Sci. Rep. doi: 10.1038/srep46658 – volume: 165 start-page: 106 year: 2007 ident: ref_20 article-title: A Human Hepatocellular in Vitro Model to Investigate Steatosis publication-title: Chem. Biol. Interact. doi: 10.1016/j.cbi.2006.11.004 – volume: 18 start-page: 296 year: 2013 ident: ref_35 article-title: DNA Methylation Analysis in Nonalcoholic Fatty Liver Disease Suggests Distinct Disease-Specific and Remodeling Signatures after Bariatric Surgery publication-title: Cell Metab. doi: 10.1016/j.cmet.2013.07.004 – volume: 31 start-page: 2723 year: 2011 ident: ref_40 article-title: Plasma Lipidomic Analysis of Stable and Unstable Coronary Artery Disease publication-title: Arter. Thromb. Vasc. Biol. doi: 10.1161/ATVBAHA.111.234096 – ident: ref_31 doi: 10.1371/annotation/9dd8c2df-1921-45b4-b3ba-8919f9068aea – volume: 82 start-page: 113 year: 2004 ident: ref_1 article-title: Phospholipid Biosynthesis in Mammalian Cells publication-title: Biochem. Cell Biol. doi: 10.1139/o03-073 – volume: 285 start-page: 18528 year: 2010 ident: ref_6 article-title: Specific Contribution of Methionine and Choline in Nutritional Nonalcoholic Steatohepatitis: Impact on Mitochondrial S-Adenosyl-l-Methionine and Glutathione publication-title: J. Biol. Chem. doi: 10.1074/jbc.M109.099333 – volume: 40 start-page: 185 year: 2004 ident: ref_19 article-title: Free Fatty Acids Promote Hepatic Lipotoxicity by Stimulating TNF-Alpha Expression via a Lysosomal Pathway publication-title: Hepatology doi: 10.1002/hep.20283 – volume: 21 start-page: 63 year: 2010 ident: ref_12 article-title: Metabolic Flux Analysis in Eukaryotes publication-title: Curr. Opin. Biotechnol. doi: 10.1016/j.copbio.2010.01.011 |
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| Title | Stable Isotopic Tracer Phospholipidomics Reveals Contributions of Key Phospholipid Biosynthetic Pathways to Low Hepatocyte Phosphatidylcholine to Phosphatidylethanolamine Ratio Induced by Free Fatty Acids |
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