Betaine supplementation is less effective than methionine restriction in correcting phenotypes of CBS deficient mice

• Published in: Journal of inherited metabolic disease Vol. 39; no. 1; pp. 39 - 46
• Main Authors: Gupta, Sapna, Wang, Liqun, Kruger, Warren D.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.01.2016; Blackwell Publishing Ltd
• Subjects: Animals; Betaine - administration & dosage; Biochemistry; Bone Density - drug effects; Cystathionine beta-Synthase - metabolism; Diet - methods; Dietary Supplements; Disease Models, Animal; Female; Homocystinuria - drug therapy; Homocystinuria - metabolism; Human Genetics; Internal Medicine; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Methionine - metabolism; Mice; Mice, Inbred C57BL; Original Article; Osteoporosis - metabolism; Pediatrics; Phenotype; Weight Gain - drug effects; Weight Loss - drug effects; tHcy Level; Regular Diet; Homocysteine; Betaine; Lean Mass
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1007/s10545-015-9883-z

Cystathionine beta synthase (CBS) deficiency is a recessive inborn error of metabolism characterized by elevated serum total homocysteine (tHcy). Betaine supplementation, which can lower tHcy by stimulating homocysteine remethylation to methionine, is often given to CBS deficient patients in combination with other treatments such as methionine restriction and supplemental B-vitamins. However, the effectiveness of betaine supplementation by itself in the treatment of CBS deficiency has not been well explored. Here, we have examined the effect of a betaine supplemented diet on the Tg-I278T Cbs −/− mouse model of CBS deficiency and compared its effectiveness to our previously published data using a methionine restricted diet. Tg-I278T Cbs −/− mice on betaine, from the time of weaning until for 240 days of age, had a 40 % decrease in mean tHcy level and a 137 % increase in serum methionine levels. Betaine-treated Tg-I278T Cbs −/− mice also exhibited increased levels of betaine-dependent homocysteine methyl transferase (BHMT), increased levels of the lipogenic enzyme stearoyl-coenzyme A desaturase (SCD-1), and increased lipid droplet accumulation in the liver. Betaine supplementation largely reversed the hair loss phenotype in Tg-I278T Cbs −/− animals, but was far less effective than methionine restriction in reversing the weight-loss, fat-loss, and osteoporosis phenotypes. Surprisingly, betaine supplementation had several negative effects in control Tg-I278T Cbs +/− mice including decreased weight gain, lean mass, and bone mineral density. Our findings indicate that while betaine supplementation does have some beneficial effects, it is not as effective as methionine restriction for reversing the phenotypes associated with severe CBS deficiency in mice.