Betaine attenuates alcoholic steatosis by restoring phosphatidylcholine generation via the phosphatidylethanolamine methyltransferase pathway.
OBJECTIVE
Previous studies in our laboratory implicated ethanol-induced decreases in hepatocellular S-adenosylmethionine to S-adenosylhomocysteine (SAM:SAH) ratios in lowering the activity of phosphatidylethanolamine methyltransferase (PEMT), which is associated with the generation of steatosis. Further in vitro studies showed that betaine supplementation could correct these alterations in the ratio as well as attenuate alcoholic steatosis. Therefore, we sought to determine whether the protective effect of betaine is via its effect on PEMT activity.


METHODS
Male Wistar rats were fed the Lieber DeCarli control or ethanol diet with or without 1% betaine supplementation for 4 weeks.


RESULTS
We observed that ethanol feeding resulted in decreased phosphatidylcholine (PC) production by a PEMT-catalyzed reaction. Betaine supplementation corrected the ethanol-induced decrease in hepatic SAM:SAH ratios and by normalizing PC production via the PEMT-mediated pathway, significantly reduced fatty infiltration associated with ethanol consumption. This restoration of hepatocellular SAM:SAH ratio by betaine supplementation was associated with increases in the activity, enzyme mass and gene expression of the enzyme, betaine homocysteine methyltransferase (BHMT), that remethylates homocysteine.


CONCLUSIONS
Betaine, by virtue of promoting an alternate remethylation pathway, restores SAM:SAH ratios that, in turn, correct the defective cellular methylation reaction catalyzed by PEMT resulting in protection against the generation of alcoholic steatosis.
Kharbanda
Kusum K
KK
VA Alcohol Research Center, Department of Veterans Affairs Medical Center, Omaha, NE 68105, USA. kkharbanda@unmc.edu
Mailliard
Mark E
ME
Baldwin
Cheryl R
CR
Beckenhauer
Harriet C
HC
Sorrell
Michael F
MF
Tuma
Dean J
DJ
D000818:Animals; D001622:Betaine / Q000008:administration & dosage*; D004032:Diet; D000431:Ethanol / Q000633:toxicity; D005235:Fatty Liver, Alcoholic / Q000201:enzymology / Q000517:prevention & control*; D008082:Lipotropic Agents / Q000008:administration & dosage*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D010713:Phosphatidylcholines / Q000378:metabolism*; D050918:Phosphatidylethanolamine N-Methyltransferase / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012435:S-Adenosylhomocysteine / Q000032:analysis; D012436:S-Adenosylmethionine / Q000032:analysis; D014280:Triglycerides / Q000032:analysis
D008082:Lipotropic Agents; D010713:Phosphatidylcholines; D014280:Triglycerides; D000431:Ethanol; D001622:Betaine; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D050918:Phosphatidylethanolamine N-Methyltransferase