title: Cystathionine beta-synthase deficiency causes fat loss in mice.
abstract: 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.
authors.affiliation: Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America.
authors.forename: Sapna
authors.initials: S
authors.lastname: Gupta
authors.forename: Warren D
authors.initials: WD
authors.lastname: Kruger
mesh_terms: D015502:Absorptiometry, Photon; D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D003541:Cystathionine beta-Synthase / Q000172:deficiency / Q000378:metabolism*; D003545:Cysteine / Q000097:blood; D005223:Fats / Q000378:metabolism*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism
chemical_list: D005223:Fats; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase; D003541:Cystathionine beta-Synthase; D005978:Glutathione; D003545:Cysteine; D000111:Acetylcysteine
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