Betaine supplementation improves the atherogenic risk factor profile in a transgenic mouse model of hyperhomocysteinemia.
OBJECTIVE
To investigate the lipotropic action of betaine on plasma lipoproteins and tissue lipids.


RESULTS
Adult mice, wild type (+/+) or heterozygous (+/-) for a disruption of the methylenetetrahydrofolate reductase (Mthfr) gene, were supplemented with betaine for 1 year and compared with mice on control diets. Outcome measures were plasma homocysteine and lipoprotein levels, aortic and liver morphology, and liver staining for 3-nitrotyrosine (oxidative stress marker) and Apolipoprotein A-I (ApoA-I). We also investigated short-term effects of supplemental betaine on plasma lipoproteins in Mthfr +/+ and +/- mice. Both genotypes showed significantly lower plasma homocysteine after long-term betaine supplementation, and lower plasma triglycerides and higher HDL-cholesterol after both short- and long-term betaine. Lipid accumulation in liver and aortic wall tended to be lower in Mthfr+/+ compared to Mthfr+/- mice and in betaine-supplemented compared to unsupplemented mice. Nitrotyrosine staining was higher and ApoA-I staining was lower in livers of Mthfr+/- compared to Mthfr+/+ mice. Betaine did not affect staining of nitrotyrosine but increased ApoA-I staining. A significant negative correlation was observed between plasma homocysteine and liver ApoA-I.


CONCLUSIONS
Mild MTHFR deficiency in mice is associated with increased risk for atherosclerotic disease. Betaine has a lipotropic effect, which is associated with a reduction in homocysteine, an increase in ApoA-I and an amelioration of the atherogenic risk profile.
Schwahn
B C
BC
Departments of Human Genetics and Pediatrics, McGill University Health Center-Montreal Children's Hospital, Montreal, Canada.
Wang
X-L
XL
Mikael
L G
LG
Wu
Q
Q
Cohn
J
J
Jiang
H
H
Maclean
K N
KN
Rozen
R
R
D000818:Animals; D030801:Animals, Genetically Modified; D001011:Aorta / Q000473:pathology; D016632:Apolipoprotein A-I / Q000187:drug effects*; D001622:Betaine / Q000494:pharmacology*; D002784:Cholesterol; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000473:pathology; D006710:Homocysteine / Q000187:drug effects*; D020138:Hyperhomocysteinemia / Q000188:drug therapy*; D007150:Immunohistochemistry; D008082:Lipotropic Agents / Q000494:pharmacology*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D051379:Mice; D013995:Time; D014280:Triglycerides / Q000097:blood; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D016632:Apolipoprotein A-I; D008082:Lipotropic Agents; D014280:Triglycerides; D006710:Homocysteine; C002744:3-nitrotyrosine; D001622:Betaine; D014443:Tyrosine; D002784:Cholesterol; D042965:Methylenetetrahydrofolate Reductase (NADPH2)