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. OBJECTIVES: 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. DESIGN: 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. CONCLUSION: 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.
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 nutrientcholine, 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. OBJECTIVES: 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 CFpatients. DESIGN: Quantification of plasma/serum choline and PC species in adult CFpatients 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 CFpatients 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. CONCLUSION: In CFpatients, hepatic and plasma homeostasis of choline and PC correlate with lung function and inflammation. Impaired hepatic PC metabolism, exemplarily shown in three CFpatients, provides an explanation for such correlations. Larger studies are required to understand the link between hepatic PC metabolism and overall clinical performance of CFpatients, and the perspective of choline substitution of these patients.
Authors: Wolfgang Bernhard; Christoph Maas; Anna Shunova; Michaela Mathes; Katrin Böckmann; Christine Bleeker; Julia Vek; Christian F Poets; Erwin Schleicher; Axel R Franz Journal: Eur J Nutr Date: 2017-06-20 Impact factor: 5.614
Authors: Jessica A Alvarez; Elizabeth Y Chong; Douglas I Walker; Joshua D Chandler; Ellen S Michalski; Ruth E Grossmann; Karan Uppal; Shuzhao Li; Jennifer K Frediani; Rabindra Tirouvanziam; ViLinh T Tran; Vin Tangpricha; Dean P Jones; Thomas R Ziegler Journal: Metabolism Date: 2017-02-11 Impact factor: 8.694
Authors: Joan I Schall; Maria R Mascarenhas; Asim Maqbool; Kelly A Dougherty; Okan Elci; Dah-Jyuu Wang; Talissa A Altes; Kevin A Hommel; Walter Shaw; Jeff Moore; Virginia A Stallings Journal: J Pediatr Gastroenterol Nutr Date: 2016-04 Impact factor: 2.839
Authors: Wolfgang Bernhard; Marco Raith; Vera Koch; Christoph Maas; Harald Abele; Christian F Poets; Axel R Franz Journal: Eur J Nutr Date: 2015-09-12 Impact factor: 5.614