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BHMT deletion results in altered sulfur‐containing amino acids, disturbed one‐carbon metabolism, elevated hepatic fat deposition, and diminished white adipose tissue mass
Author(s) -
Teng YaWen,
Zeisel Steven H
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.915.8
Subject(s) - chemistry , choline , triglyceride , phosphatidylcholine , medicine , endocrinology , steatosis , homocysteine , fatty liver , metabolism , biochemistry , cholesterol , phospholipid , biology , membrane , disease
Human single nucleotide polymorphisms (SNPs) in the betaine:homocysteine methyltransferase (BHMT) gene have been identified. Our laboratory generated a mouse with the gene encoding BHMT deleted ( Bhmt −/− ) to study the potential functional effects of such SNPs. Mice were fed a AIN76A diet. Homocysteine, cysteine, S‐adenosylhomocysteine were measured using HPLC; choline metabolites using LC/MS; triglyceride and phosphatidylcholine using GC. Bhmt −/− mice had hyperhomocysteinemia, hypocysteinemia, and elevated hepatic S‐adenosylhomocysteine (p<0.01) as compared to Bhmt +/+ mice. Bhmt −/− mice had elevated betaine in various tissues, but reduced choline, phosphocholine, phosphatidylcholine, and glycerophosphocholine in the liver (p<0.05) as compared to Bhmt +/+ mice. Starting at 5 weeks of age, Bhmt −/− mice had reduced body weight and fat mass with significant reductions in the gonadal, inguinal and retroperitoneal fat pads (p<0.01). Bhmt −/− mice had higher food intake (p<0.01), higher energy expenditure (p<0.05), but no difference in the activity level when compared to Bhmt +/+ mice. Bhmt −/− mice also had elevated liver mass and hepatic triglyceride deposition, which were accompanied by reduced hepatic and plasma phosphatidylcholine, and reduced plasma cholesterol (p<0.01). We are currently studying the underlying mechanisms for these effects of BHMT deletion.