title: Hyperhomocysteinemia due to cystathionine beta synthase deficiency induces dysregulation of genes involved in hepatic lipid homeostasis in mice.
abstract: OBJECTIVE
  Cystathionine beta synthase (CBS) deficiency leads to severe hyperhomocysteinemia, which confers diverse clinical manifestations, notably fatty liver. Recently, abnormal lipid metabolism has been demonstrated in CBS-deficient mice, a murine model of severe hyperhomocysteinemia. To gain further insights into effects of CBS deficiency on hepatic cholesterol metabolism, the expression of hepatic genes involved in biosynthesis, uptake and efflux was determined in CBS-deficient mice.
  
  
  METHODS
  Gene expression analysis was performed on liver of CBS-deficient mice using quantitative real-time PCR.
  
  
  RESULTS
  We found that CBS-deficiency in liver mice significantly increases expression of genes induced by endoplasmic reticulum stress and genes that regulate the expression of enzymes required for cholesterol and fatty acid biosynthesis and uptake, notably the scavenger receptor class B type I (SR-BI), concomitant with overexpression of SR-BI at the protein level. Moreover, we also found increased mRNA levels of ABCG5, ABCG8, ABCG1 and ABCA1, which play important roles in reverse cholesterol transport, associated with an upregulation of liver X receptors and a downregulation of the peroxisome proliferators-activated receptor alpha.
  
  
  CONCLUSIONS
  We found that several ATP-binding cassette transporters and nuclear hormone receptors involved in liver lipid homeostasis are differentially expressed in liver of CBS-deficient mice.
authors.affiliation: EA 3508, Université Paris 7 - Denis Diderot, Case 7104, 2 Place Jussieu, 75251 Paris cedex 05, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Hamelet
authors.forename: Karine
authors.initials: K
authors.lastname: Demuth
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Paul
authors.forename: Jean-Maurice
authors.initials: JM
authors.lastname: Delabar
authors.forename: Nathalie
authors.initials: N
authors.lastname: Janel
mesh_terms: D000818:Animals; D001483:Base Sequence; D002784:Cholesterol / Q000378:metabolism; D003541:Cystathionine beta-Synthase / Q000172:deficiency* / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006710:Homocysteine / Q000097:blood; D006712:Homocystinuria / Q000150:complications / Q000235:genetics / Q000378:metabolism; D020138:Hyperhomocysteinemia / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D006710:Homocysteine; D002784:Cholesterol; D003541:Cystathionine beta-Synthase