title: Betaine administration corrects ethanol-induced defective VLDL secretion.
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.
authors.affiliation: Research Service (151), Department of Veterans Affairs Medical Center, 4101 Woolworth Avenue, Omaha, NE 68105, USA. kkharbanda@unmc.edu
authors.forename: Kusum K
authors.initials: KK
authors.lastname: Kharbanda
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Todero
authors.forename: Brian W
authors.initials: BW
authors.lastname: Ward
authors.forename: John J
authors.initials: JJ
authors.lastname: Cannella
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Tuma
mesh_terms: D000818:Animals; D001622:Betaine / Q000008:administration & dosage* / Q000494:pharmacology; D000431:Ethanol / Q000633:toxicity*; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008082:Lipotropic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D010713:Phosphatidylcholines / Q000378:metabolism; D051381:Rats
chemical_list: D008079:Lipoproteins, VLDL; D008082:Lipotropic Agents; D010713:Phosphatidylcholines; D000431:Ethanol; D001622:Betaine