title: Plasma phosphatidylcholine alterations in cystic fibrosis patients: impaired metabolism and correlation with lung function and inflammation.
abstract: BACKGROUND
  Liver impairment, ranging from steatosis to cirrhosis, is frequent in cystic fibrosis (CF) patients and is becoming increasingly significant due to their improved life expectancy. One aspect of hepatic alterations is caused by increased fecal loss of the essential nutrient choline, following enterohepatic bile phosphatidylcholine (PC) cycle impairment. Hepatic PC synthesis, both de novo and via phosphatidylethanolamine-N-methyl-transferase (PEMT), is essential for very low-density lipoprotein (VLDL) secretion. VLDL-PC in particular contributes to the organism's supply with polyunsaturated fatty acids (LC-PUFA), namely arachidonic (C20:4) and docosahexaenoic acid (C22:6). Consequently, choline deprivation and altered hepatic PC metabolism may affect plasma PC homeostasis and extrahepatic organ function.
  
  
  OBJECTIVE
  To investigate relationships between altered plasma choline and PC homeostasis and markers of lung function and inflammation in CF. To assess alterations in hepatic choline and PC metabolism of CF patients.
  
  
  METHODS
  Quantification of plasma/serum choline and PC species in adult CF patients compared to controls. Correlation of PC with forced expiratory vital capacity (FEV1) and interleukin 6 (IL-6) concentrations. Analysis of choline and PC metabolism in CF compared to controls, using deuterated choline ([D₉-methyl]-choline) labeling in vivo.
  
  
  RESULTS
  Mean choline and PC concentrations in CF patients were lower than in controls. Choline and PC concentrations as well as fractions of C22:6-PC and C20:4-PC correlated directly with FEV1, but inversely with IL-6. Plasma concentrations of deuterated PC were decreased for both pathways, whereas only in PC synthesized via PEMT precursor enrichment was decreased.
  
  
  CONCLUSIONS
  In CF patients, hepatic and plasma homeostasis of choline and PC correlate with lung function and inflammation. Impaired hepatic PC metabolism, exemplarily shown in three CF patients, provides an explanation for such correlations. Larger studies are required to understand the link between hepatic PC metabolism and overall clinical performance of CF patients, and the perspective of choline substitution of these patients.
authors: Department of Neonatology, Faculty of Medicine, Eberhard-Karls-University, Tübingen, Germany.
authors: Judith
authors: J
authors: Grothe
authors: Joachim
authors: J
authors: Riethmüller
authors: Sandra M
authors: SM
authors: Tschürtz
authors: Marco
authors: M
authors: Raith
authors: Chris J
authors: CJ
authors: Pynn
authors: Dieter
authors: D
authors: Stoll
authors: Wolfgang
authors: W
authors: Bernhard
mesh_terms: D000328:Adult; D016718:Arachidonic Acid / Q000737:chemistry / Q000378:metabolism; D001622:Betaine / Q000097:blood; D002794:Choline / Q000097:blood / Q000378:metabolism; D003550:Cystic Fibrosis / Q000378:metabolism / Q000473:pathology*; D003903:Deuterium / Q000737:chemistry; D004281:Docosahexaenoic Acids / Q000737:chemistry / Q000378:metabolism; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000097:blood; D007553:Isotope Labeling; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000502:physiology*; D008297:Male; D010713:Phosphatidylcholines / Q000097:blood* / Q000378:metabolism; D050918:Phosphatidylethanolamine N-Methyltransferase / Q000378:metabolism; D055815:Young Adult
chemical_list: D015850:Interleukin-6; D010713:Phosphatidylcholines; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D001622:Betaine; D003903:Deuterium; D050918:Phosphatidylethanolamine N-Methyltransferase; D002794:Choline