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Cystathionine Beta-Synthase Deficiency Causes Fat Loss in Mice

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 th...

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Autores principales: Gupta, Sapna, Kruger, Warren D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3214081/
https://www.ncbi.nlm.nih.gov/pubmed/22096601
http://dx.doi.org/10.1371/journal.pone.0027598
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author Gupta, Sapna
Kruger, Warren D.
author_facet Gupta, Sapna
Kruger, Warren D.
author_sort Gupta, Sapna
collection PubMed
description 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.
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spelling pubmed-32140812011-11-17 Cystathionine Beta-Synthase Deficiency Causes Fat Loss in Mice Gupta, Sapna Kruger, Warren D. PLoS One Research Article 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. Public Library of Science 2011-11-11 /pmc/articles/PMC3214081/ /pubmed/22096601 http://dx.doi.org/10.1371/journal.pone.0027598 Text en Gupta, Kruger.
spellingShingle Research Article
Gupta, Sapna
Kruger, Warren D.
Cystathionine Beta-Synthase Deficiency Causes Fat Loss in Mice
title Cystathionine Beta-Synthase Deficiency Causes Fat Loss in Mice
title_full Cystathionine Beta-Synthase Deficiency Causes Fat Loss in Mice
title_fullStr Cystathionine Beta-Synthase Deficiency Causes Fat Loss in Mice
title_full_unstemmed Cystathionine Beta-Synthase Deficiency Causes Fat Loss in Mice
title_short Cystathionine Beta-Synthase Deficiency Causes Fat Loss in Mice
title_sort cystathionine beta-synthase deficiency causes fat loss in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3214081/
https://www.ncbi.nlm.nih.gov/pubmed/22096601
http://dx.doi.org/10.1371/journal.pone.0027598
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