title: Hepatic very-low-density lipoprotein and apolipoprotein B production are increased following in vivo induction of betaine-homocysteine S-methyltransferase.
abstract: We have previously reported a positive correlation between the expression of BHMT (betaine-homocysteine S-methyltransferase) and ApoB (apolipoprotein B) in rat hepatoma McA (McArdle RH-7777) cells [Sowden, Collins, Smith, Garrow, Sparks and Sparks (1999) Biochem. J. 341, 639-645]. To examine whether a similar relationship occurs in vivo, hepatic BHMT expression was induced by feeding rats a Met (L-methionine)-restricted betaine-containing diet, and parameters of ApoB metabolism were evaluated. There were no generalized metabolic abnormalities associated with Met restriction for 7 days, as evidenced by control levels of serum glucose, ketones, alanine aminotransferase and L-homocysteine levels. Betaine plus the Met restriction resulted in lower serum insulin and non-esterified fatty acid levels. Betaine plus Met restriction induced hepatic BHMT 4-fold and ApoB mRNA 3-fold compared with Met restriction alone. No changes in percentage of edited ApoB mRNA were observed on the test diets. An increase in liver ApoB mRNA correlated with an 82% and 46% increase in ApoB and triacylglycerol production respectively using in vivo Triton WR 1339. Increased secretion of VLDL (very-low-density lipoprotein) with Met restriction plus betaine was associated with a 45% reduction in liver triacylglycerol compared with control. Nuclear run-off assays established that transcription of both bhmt and apob genes was also increased in Met-restricted plus betaine diets. No change in ApoB mRNA stability was detected in BHMT-transfected McA cells. Hepatic ApoB and BHMT mRNA levels were also increased by 1.8- and 3-fold respectively by betaine supplementation of Met-replete diets. Since dietary betaine increased ApoB mRNA, VLDL ApoB and triacylglycerol production and decreased hepatic triacylglycerol, results suggest that induction of apob transcription may provide a potential mechanism for mobilizing hepatic triacylglycerol by increasing ApoB available for VLDL assembly and secretion.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. Janet_Sparks@urmc.rochester.edu
authors.forename: Janet D
authors.initials: JD
authors.lastname: Sparks
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Collins
authors.forename: Doru V
authors.initials: DV
authors.lastname: Chirieac
authors.forename: Joanne
authors.initials: J
authors.lastname: Cianci
authors.forename: Jenny
authors.initials: J
authors.lastname: Jokinen
authors.forename: Mark P
authors.initials: MP
authors.lastname: Sowden
authors.forename: Chad A
authors.initials: CA
authors.lastname: Galloway
authors.forename: Charles E
authors.initials: CE
authors.lastname: Sparks
mesh_terms: D000375:Aging; D000818:Animals; D001055:Apolipoproteins B / Q000096:biosynthesis* / Q000235:genetics; D001622:Betaine / Q000494:pharmacology; D050940:Betaine-Homocysteine S-Methyltransferase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004032:Diet; D004790:Enzyme Induction; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D048788:Growth and Development; D008079:Lipoproteins, VLDL / Q000096:biosynthesis*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008715:Methionine / Q000172:deficiency; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051779:Sterol Regulatory Element Binding Proteins / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D001055:Apolipoproteins B; D008079:Lipoproteins, VLDL; D012333:RNA, Messenger; D051779:Sterol Regulatory Element Binding Proteins; D001622:Betaine; D008715:Methionine; D050940:Betaine-Homocysteine S-Methyltransferase