BHMT deletion results in altered sulfur‐containing amino acids, disturbed one‐carbon metabolism, elevated hepatic fat deposition, and diminished white adipose tissue mass

Abstract

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.