Cystathionine beta-synthase deficiency causes fat loss in mice

• Published in: PloS one 2011-11, Vol.6 (11), p.e27598-e27598
• Main Authors: Gupta, Sapna, Kruger, Warren D
• Format: Article
• Language: English
• Subjects: Absorptiometry, Photon; Acetylcysteine; Acetylcysteine - pharmacology; Adipocytes; Allium; Animals; Biochemistry; Biology; Blotting, Western; Body fat; Body mass; Body Mass Index; Body size; Body Weight - drug effects; Body Weight - genetics; Cancer; Catalysis; Cystathionine b-synthase; Cystathionine beta-Synthase - deficiency; Cystathionine beta-Synthase - metabolism; Cysteine; Cysteine - blood; Cystine; Deoxyribonucleic acid; Desaturase; Diet; DNA; DNA methylation; Drinking water; Enzymes; Fats - metabolism; Female; Food; Gene expression; Genomes; Glutathione; Glutathione - metabolism; Homocysteine; Insulin; Liver; Male; Mice; Mice, Knockout; mRNA; Mutation; Obesity; Osteoporosis; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Stearoyl-CoA desaturase; Stearoyl-CoA Desaturase - genetics; Stearoyl-CoA Desaturase - metabolism; Studies
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0027598

Cystathionine beta synthase (CBS) is the rate-limiting enzyme responsible for the de novo synthesis of cysteine. Patients with CBS deficiency have greatly elevated plasma total homocysteine (tHcy), decreased levels of plasma total cysteine (tCys), and often a marfanoid appearance characterized by thinness and low body-mass index (BMI). Here, we characterize the growth and body mass characteristics of CBS deficient TgI278T Cbs(-/-) mice and show that these animals have significantly decreased fat mass and tCys compared to heterozygous sibling mice. The decrease in fat mass is accompanied by a 34% decrease in liver glutathione (GSH) along with a significant decrease in liver mRNA and protein for the critical fat biosynthesizing enzyme Stearoyl CoA desaturase-1 (Scd-1). Because plasma tCys has been positively associated with fat mass in humans, we tested the hypothesis that decreased tCys in TgI278T Cbs(-/-) mice was the cause of the lean phenotype by placing the animals on water supplemented with N-acetyl cysteine (NAC) from birth to 240 days of age. Although NAC treatment in TgI278T Cbs(-/-) mice caused significant increase in serum tCys and liver GSH, there was no increase in body fat content or in liver Scd-1 levels. Our results show that lack of CBS activity causes loss of fat mass, and that this effect appears to be independent of low serum tCys.