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Betaine administration corrects ethanol-induced defective VLDL secretion

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Abstract

Our previous studies, demonstrating ethanol-induced alterations in phosphatidylcholine (PC) synthesis via the phosphatidylethanolamine methyltransferase (PEMT) pathway, implicated a defect in very low-density lipoprotein (VLDL) secretion in the pathogenesis of hepatic steatosis. The objective of this study was to determine whether VLDL secretion was reduced by chronic ethanol consumption and whether betaine supplementation, that restores PEMT activity and prevents the development of alcoholic steatosis, could normalize VLDL secretion. The VLDL secretion in rats fed with control, ethanol and the betaine supplemented diets was determined using Triton WR-1339 to inhibit plasma VLDL metabolism. We observed reduced VLDL production rates in chronic alcohol-fed rats compared to control animals. Supplementation of betaine in the ethanol diet increased VLDL production rate to values significantly higher than those observed in the control diet-fed rats. To conclude, chronic ethanol consumption impairs PC generation via the PEMT pathway resulting in diminished VLDL secretion which contributes to the development of hepatic steatosis. By increasing PEMT-mediated PC generation, betaine results in increased fat export from the liver and attenuates the development of alcoholic fatty liver.

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Fig. 1

Abbreviations

apo B:

Apolipoprotein B

PC:

Phosphatidylcholine

PEMT:

Phosphatidylethanolamine methyltransferase

SAM:

S-adenosylmethionine

SAH:

S-adenosylhomocysteine

TG:

Triglyceride

VLDL:

Very low-density lipoproteins

References

  1. Kharbanda KK, Mailliard ME, Baldwin CR et al (2007) Betaine attenuates alcoholic steatosis by restoring phosphatidylcholine generation via the phosphatidylethanolamine methyltransferase pathway. J Hepatol 46:314–321. doi:10.1016/j.jhep.2006.08.024

    Article  PubMed  CAS  Google Scholar 

  2. Nishimaki-Mogami T, Yao Z, Fujimori K (2002) Inhibition of phosphatidylcholine synthesis via the phosphatidylethanolamine methylation pathway impairs incorporation of bulk lipids into VLDL in cultured rat hepatocytes. J Lipid Res 43:1035–1045. doi:10.1194/jlr.M100354-JLR200

    Article  PubMed  CAS  Google Scholar 

  3. Noga AA, Zhao Y, Vance DE (2002) An unexpected requirement for phosphatidylethanolamine N-methyltransferase in the secretion of very low density lipoproteins. J Biol Chem 277:42358–42365. doi:10.1074/jbc.M204542200

    Article  PubMed  CAS  Google Scholar 

  4. Lieber CS, DeCarli LM (1989) Liquid diet technique of ethanol administration: 1989 update. Alcohol Alcohol 24:197–211

    PubMed  CAS  Google Scholar 

  5. Barak AJ, Beckenhauer HC, Tuma DJ (1985) Ethanol feeding inhibits the activity of N5-methyltetrahydrofolate-homocysteine methyltransferase in the rat. IRCS Med Sci 13:760–761

    CAS  Google Scholar 

  6. Barak AJ, Beckenhauer HC, Mailliard ME et al (2003) Betaine lowers elevated S-adenosylhomocysteine levels in hepatocytes from ethanol-fed rats. J Nutr 133:2845–2848

    PubMed  CAS  Google Scholar 

  7. Vance DE, Ridgway ND (1988) The methylation of phosphatidylethanolamine. Prog Lipid Res 27:61–79. doi:10.1016/0163-7827(88)90005-7

    Article  PubMed  CAS  Google Scholar 

  8. DeLong CJ, Shen YJ, Thomas MJ et al (1999) Molecular distinction of phosphatidylcholine synthesis between the CDP-choline pathway and phosphatidylethanolamine methylation pathway. J Biol Chem 274:29683–29688. doi:10.1074/jbc.274.42.29683

    Article  PubMed  CAS  Google Scholar 

  9. Zhu X, Song J, Mar MH et al (2003) Phosphatidylethanolamine-N-methyltransferase (PEMT) knockout mice have hepatic steatosis and abnormal hepatic choline metabolite concentrations despite ingesting a recommended dietary intake of choline. Biochem J 370:987–993. doi:10.1042/BJ20021523

    Article  PubMed  CAS  Google Scholar 

  10. Chirieac DV, Davidson NO, Sparks CE et al (2006) PI3-kinase activity modulates apo B available for hepatic VLDL production in apobec-1-/- mice. Am J Physiol Gastrointest Liver Physiol 291:G382–G388. doi:10.1152/ajpgi.00472.2005

    Article  PubMed  CAS  Google Scholar 

  11. Soler-Argilaga C, Danon A, Wilcox HG et al (1976) Effects of sex on formation and properties of plasma very low density lipoprotein in vivo. Lipids 11:517–525. doi:10.1007/BF02532896

    Article  PubMed  CAS  Google Scholar 

  12. Venkatesan S, Ward RJ, Peters TJ (1988) Effect of chronic ethanol feeding on the hepatic secretion of very-low-density lipoproteins. Biochim Biophys Acta 960:61–66

    PubMed  CAS  Google Scholar 

  13. Sparks JD, Collins HL, Chirieac DV et al (2006) Hepatic VLDL and apolipoprotein B production are increased following in vivo induction of betaine-homocysteine S-methyltransferase. Biochem J 395:363–371. doi:10.1042/BJ20051966

    Article  PubMed  CAS  Google Scholar 

  14. Song J, da Costa KA, Fischer LM et al (2005) Polymorphism of the PEMT gene and susceptibility to nonalcoholic fatty liver disease (NAFLD). FASEB J 19:1266–1271. doi:10.1096/fj.04-3580com

    Article  PubMed  CAS  Google Scholar 

  15. Dong H, Wang J, Li C et al (2007) The phosphatidylethanolamine N-methyltransferase gene V175 M single nucleotide polymorphism confers the susceptibility to NASH in Japanese population. J Hepatol 46:915–920. doi:10.1016/j.jhep.2006.12.012

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors thank Harriet Beckenhauer for the excellent technical assistance. This material is based upon work supported by the Merit Review grant (KKK) from the Office of Research and Development Medical Research Service, Department of Veterans Affairs.

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Correspondence to Kusum K. Kharbanda.

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Kharbanda, K.K., Todero, S.L., Ward, B.W. et al. Betaine administration corrects ethanol-induced defective VLDL secretion. Mol Cell Biochem 327, 75–78 (2009). https://doi.org/10.1007/s11010-009-0044-2

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  • DOI: https://doi.org/10.1007/s11010-009-0044-2

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