Betaine attenuates alcoholic steatosis by restoring phosphatidylcholine generation via the phosphatidylethanolamine methyltransferase pathway

Kusum Kharbanda, Mark E Mailliard, Cheryl R. Baldwin, Harriet C. Beckenhauer, Michael Floyd Sorrell, Dean J. Tuma

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

Background/Aims: 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.

Original languageEnglish (US)
Pages (from-to)314-321
Number of pages8
JournalJournal of Hepatology
Volume46
Issue number2
DOIs
StatePublished - Feb 1 2007

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Phosphatidylethanolamine N-Methyltransferase
Betaine
Phosphatidylcholines
S-Adenosylhomocysteine
S-Adenosylmethionine
Ethanol
Betaine-Homocysteine S-Methyltransferase
Homocysteine
Enzymes
Methylation
Wistar Rats
Diet
Gene Expression
Liver

Keywords

  • Alcohol
  • Apoptosis
  • Betaine
  • Liver
  • Methylation
  • Phosphatidylethanolamine methyltransferases
  • S-adenosylhomocysteine
  • S-adenosylmethionine

ASJC Scopus subject areas

  • Hepatology

Cite this

Betaine attenuates alcoholic steatosis by restoring phosphatidylcholine generation via the phosphatidylethanolamine methyltransferase pathway. / Kharbanda, Kusum; Mailliard, Mark E; Baldwin, Cheryl R.; Beckenhauer, Harriet C.; Sorrell, Michael Floyd; Tuma, Dean J.

In: Journal of Hepatology, Vol. 46, No. 2, 01.02.2007, p. 314-321.

Research output: Contribution to journalArticle

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AB - Background/Aims: 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.

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