Phosphatidylethanolamine N-methyltransferase (PEMT) knockout mice have hepatic steatosis and abnormal hepatic choline metabolite concentrations despite ingesting a recommended dietary intake of choline.
Choline is an essential nutrient for humans and is derived from the diet as well as from de novo synthesis involving methylation of phosphatidylethanolamine catalysed by the enzyme phosphatidylethanolamine N -methyltransferase (PEMT). This is the only known pathway that produces new choline molecules. We used mice with a disrupted Pemt-2 gene (which encodes PEMT; Pemt (-/-)) that have previously been shown to possess no hepatic PEMT enzyme. Male, female and pregnant Pemt (-/-) and wild-type mice ( n =5-6 per diet group) were fed diets of different choline content (deficient, control, and supplemented). Livers were collected and analysed for choline metabolites, steatosis, and apoptotic [terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labelling (TUNEL)] positive cells. We found that, in livers of Pemt (-/-) mice fed any of the diets, there was hepatic steatosis and significantly higher occurrence of TUNEL positive cells compared with wild-type controls. In male, female and pregnant mice, liver phosphatidylcholine concentrations were significantly decreased in Pemt (-/-) choline deficient and in Pemt (-/-) choline control groups but returned to normal in Pemt (-/-) choline supplemented groups. Phosphocholine concentrations in liver were significantly diminished in knockout mice even when choline was supplemented to above dietary requirements. These results show that PEMT normally supplies a significant portion of the daily choline requirement in the mouse and, when this pathway is knocked out, mice are unable to attain normal concentrations of all choline metabolites even with a supplemental source of dietary choline.
Zhu
Xiaonan
X
Department of Nutrition, CB #7461, School of Public Health, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7400, USA.
Song
Jiannan
J
Mar
Mei-Heng
MH
Edwards
Lloyd J
LJ
Zeisel
Steven H
SH
D000818:Animals; D017209:Apoptosis; D002794:Choline / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D053938:DNA Fragmentation; D004032:Diet; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D050918:Phosphatidylethanolamine N-Methyltransferase; D011247:Pregnancy; D014280:Triglycerides / Q000378:metabolism
D014280:Triglycerides; D008780:Methyltransferases; C494489:PEMT protein, human; D050918:Phosphatidylethanolamine N-Methyltransferase; D002794:Choline