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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Autor*in:	Kang-Yu Peng [verfasserIn] Christopher K Barlow [verfasserIn] Helene Kammoun [verfasserIn] Natalie A Mellett [verfasserIn] Jacquelyn M Weir [verfasserIn] Andrew J Murphy [verfasserIn] Mark A Febbraio [verfasserIn] Peter J Meikle [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	lipidomics free fatty acid steatosis flux analysis CDP-choline pathway CDP-ethanolamine pathway

Übergeordnetes Werk:	In: Metabolites - MDPI AG, 2012, 11(2021), 3, p 188
Übergeordnetes Werk:	volume:11 ; year:2021 ; number:3, p 188

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/metabo11030188

Katalog-ID:	DOAJ062917331

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245	1	0	\|a 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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520			\|a 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 <i<N</i<-methyl transferase (PEMT) pathway was restricted by low endogenous methionine and consequently low <i<S</i<-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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allfields	10.3390/metabo11030188 doi (DE-627)DOAJ062917331 (DE-599)DOAJ5ce77a6cc4864340ad96bdf2249349c3 DE-627 ger DE-627 rakwb eng QR1-502 Kang-Yu Peng verfasserin aut Stable Isotopic Tracer Phospholipidomics Reveals Contributions of Key Phospholipid Biosynthetic Pathways to Low Hepatocyte Phosphatidylcholine to Phosphatidylethanolamine Ratio Induced by Free Fatty Acids 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 <i<N</i<-methyl transferase (PEMT) pathway was restricted by low endogenous methionine and consequently low <i<S</i<-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. lipidomics free fatty acid steatosis flux analysis CDP-choline pathway CDP-ethanolamine pathway Microbiology Christopher K Barlow verfasserin aut Helene Kammoun verfasserin aut Natalie A Mellett verfasserin aut Jacquelyn M Weir verfasserin aut Andrew J Murphy verfasserin aut Mark A Febbraio verfasserin aut Peter J Meikle verfasserin aut In Metabolites MDPI AG, 2012 11(2021), 3, p 188 (DE-627)718627164 (DE-600)2662251-8 22181989 nnns volume:11 year:2021 number:3, p 188 https://doi.org/10.3390/metabo11030188 kostenfrei https://doaj.org/article/5ce77a6cc4864340ad96bdf2249349c3 kostenfrei https://www.mdpi.com/2218-1989/11/3/188 kostenfrei https://doaj.org/toc/2218-1989 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021 3, p 188
spelling	10.3390/metabo11030188 doi (DE-627)DOAJ062917331 (DE-599)DOAJ5ce77a6cc4864340ad96bdf2249349c3 DE-627 ger DE-627 rakwb eng QR1-502 Kang-Yu Peng verfasserin aut Stable Isotopic Tracer Phospholipidomics Reveals Contributions of Key Phospholipid Biosynthetic Pathways to Low Hepatocyte Phosphatidylcholine to Phosphatidylethanolamine Ratio Induced by Free Fatty Acids 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 <i<N</i<-methyl transferase (PEMT) pathway was restricted by low endogenous methionine and consequently low <i<S</i<-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. lipidomics free fatty acid steatosis flux analysis CDP-choline pathway CDP-ethanolamine pathway Microbiology Christopher K Barlow verfasserin aut Helene Kammoun verfasserin aut Natalie A Mellett verfasserin aut Jacquelyn M Weir verfasserin aut Andrew J Murphy verfasserin aut Mark A Febbraio verfasserin aut Peter J Meikle verfasserin aut In Metabolites MDPI AG, 2012 11(2021), 3, p 188 (DE-627)718627164 (DE-600)2662251-8 22181989 nnns volume:11 year:2021 number:3, p 188 https://doi.org/10.3390/metabo11030188 kostenfrei https://doaj.org/article/5ce77a6cc4864340ad96bdf2249349c3 kostenfrei https://www.mdpi.com/2218-1989/11/3/188 kostenfrei https://doaj.org/toc/2218-1989 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021 3, p 188
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allfieldsGer	10.3390/metabo11030188 doi (DE-627)DOAJ062917331 (DE-599)DOAJ5ce77a6cc4864340ad96bdf2249349c3 DE-627 ger DE-627 rakwb eng QR1-502 Kang-Yu Peng verfasserin aut Stable Isotopic Tracer Phospholipidomics Reveals Contributions of Key Phospholipid Biosynthetic Pathways to Low Hepatocyte Phosphatidylcholine to Phosphatidylethanolamine Ratio Induced by Free Fatty Acids 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 <i<N</i<-methyl transferase (PEMT) pathway was restricted by low endogenous methionine and consequently low <i<S</i<-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. lipidomics free fatty acid steatosis flux analysis CDP-choline pathway CDP-ethanolamine pathway Microbiology Christopher K Barlow verfasserin aut Helene Kammoun verfasserin aut Natalie A Mellett verfasserin aut Jacquelyn M Weir verfasserin aut Andrew J Murphy verfasserin aut Mark A Febbraio verfasserin aut Peter J Meikle verfasserin aut In Metabolites MDPI AG, 2012 11(2021), 3, p 188 (DE-627)718627164 (DE-600)2662251-8 22181989 nnns volume:11 year:2021 number:3, p 188 https://doi.org/10.3390/metabo11030188 kostenfrei https://doaj.org/article/5ce77a6cc4864340ad96bdf2249349c3 kostenfrei https://www.mdpi.com/2218-1989/11/3/188 kostenfrei https://doaj.org/toc/2218-1989 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021 3, p 188
allfieldsSound	10.3390/metabo11030188 doi (DE-627)DOAJ062917331 (DE-599)DOAJ5ce77a6cc4864340ad96bdf2249349c3 DE-627 ger DE-627 rakwb eng QR1-502 Kang-Yu Peng verfasserin aut Stable Isotopic Tracer Phospholipidomics Reveals Contributions of Key Phospholipid Biosynthetic Pathways to Low Hepatocyte Phosphatidylcholine to Phosphatidylethanolamine Ratio Induced by Free Fatty Acids 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 <i<N</i<-methyl transferase (PEMT) pathway was restricted by low endogenous methionine and consequently low <i<S</i<-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. lipidomics free fatty acid steatosis flux analysis CDP-choline pathway CDP-ethanolamine pathway Microbiology Christopher K Barlow verfasserin aut Helene Kammoun verfasserin aut Natalie A Mellett verfasserin aut Jacquelyn M Weir verfasserin aut Andrew J Murphy verfasserin aut Mark A Febbraio verfasserin aut Peter J Meikle verfasserin aut In Metabolites MDPI AG, 2012 11(2021), 3, p 188 (DE-627)718627164 (DE-600)2662251-8 22181989 nnns volume:11 year:2021 number:3, p 188 https://doi.org/10.3390/metabo11030188 kostenfrei https://doaj.org/article/5ce77a6cc4864340ad96bdf2249349c3 kostenfrei https://www.mdpi.com/2218-1989/11/3/188 kostenfrei https://doaj.org/toc/2218-1989 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021 3, p 188
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callnumber-first	Q - Science
author	Kang-Yu Peng
spellingShingle	Kang-Yu Peng misc QR1-502 misc lipidomics misc free fatty acid misc steatosis misc flux analysis misc CDP-choline pathway misc CDP-ethanolamine pathway misc Microbiology 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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topic_title	QR1-502 Stable Isotopic Tracer Phospholipidomics Reveals Contributions of Key Phospholipid Biosynthetic Pathways to Low Hepatocyte Phosphatidylcholine to Phosphatidylethanolamine Ratio Induced by Free Fatty Acids lipidomics free fatty acid steatosis flux analysis CDP-choline pathway CDP-ethanolamine pathway
topic	misc QR1-502 misc lipidomics misc free fatty acid misc steatosis misc flux analysis misc CDP-choline pathway misc CDP-ethanolamine pathway misc Microbiology
topic_unstemmed	misc QR1-502 misc lipidomics misc free fatty acid misc steatosis misc flux analysis misc CDP-choline pathway misc CDP-ethanolamine pathway misc Microbiology
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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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title_full	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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title_sort	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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title_auth	Stable Isotopic Tracer Phospholipidomics Reveals Contributions of Key Phospholipid Biosynthetic Pathways to Low Hepatocyte Phosphatidylcholine to Phosphatidylethanolamine Ratio Induced by Free Fatty Acids
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 <i<N</i<-methyl transferase (PEMT) pathway was restricted by low endogenous methionine and consequently low <i<S</i<-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.
abstractGer	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 <i<N</i<-methyl transferase (PEMT) pathway was restricted by low endogenous methionine and consequently low <i<S</i<-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.
abstract_unstemmed	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 <i<N</i<-methyl transferase (PEMT) pathway was restricted by low endogenous methionine and consequently low <i<S</i<-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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title_short	Stable Isotopic Tracer Phospholipidomics Reveals Contributions of Key Phospholipid Biosynthetic Pathways to Low Hepatocyte Phosphatidylcholine to Phosphatidylethanolamine Ratio Induced by Free Fatty Acids
url	https://doi.org/10.3390/metabo11030188 https://doaj.org/article/5ce77a6cc4864340ad96bdf2249349c3 https://www.mdpi.com/2218-1989/11/3/188 https://doaj.org/toc/2218-1989
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By contrast, the phosphatidylethanolamine <i<N</i<-methyl transferase (PEMT) pathway was restricted by low endogenous methionine and consequently low <i<S</i<-adenosylmethionine, which resulted in a concomitant decrease in phosphatidylcholine and accumulation of phosphatidylethanolamine. 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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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