Cysteinemia, rather than homocysteinemia, is associated with plasma apolipoprotein A-I levels in hyperhomocysteinemia: lipid metabolism in cystathionine beta-synthase deficiency.
OBJECTIVE
Genetic and dietary hyperhomocysteinemia has been found to decrease high density lipoproteins (HDL) and their apolipoprotein A1 (APOA1). To test the hypothesis that the presence of cysteine could normalize HDL levels in hyperhomocysteinemic cystathionine beta-synthase (Cbs)-deficient mice and that the inclusion of glycine would block this effect.


METHODS
Lipids and HDL cholesterol were studied in Cbs-deficient mice and wild-type animals fed a low-methionine diet supplemented with cysteine and glycine and in Cbs-deficient mice on the same diet supplemented only with cysteine.


RESULTS
Triglyceride and homocysteine levels were significantly decreased and increased, respectively in Cbs-deficient mice irrespective of treatment. However, plasma cholesterol, glucose and APOA1 were significantly decreased in homozygous Cbs-deficient mice when they received the cysteine and glycine-enriched beverage. This group of mice also showed decreased mRNA levels and increased hepatic content of APOA1 protein, the latter increase was observed in endothelial cells. A significant, inverse relationship was observed between plasma and hepatic APOA1 concentrations while a positive one was found between plasma levels of cysteine and APOA1.


CONCLUSIONS
These data suggest an altered hepatic management of APOA1 and that cysteine may be involved in the control of this apolipoprotein at this level. Overall these findings represent a new aspect of dietary regulation of HDL at the hepatic transendothelial transport.
Nuño-Ayala
Mario
M
Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto Aragonés de Ciencias de la Salud, Universidad de Zaragoza-Salud del Gobierno de Aragón, Spain.
Guillén
Natalia
N
Navarro
María A
MA
Lou-Bonafonte
Jose M
JM
Arnal
Carmen
C
Gascón
Sonia
S
Barranquero
Cristina
C
Godino
Javier
J
Royo-Cañas
María
M
Sarría
Alfonso J
AJ
Guzmán
Mario A
MA
Hernandez
Esther
E
Bregante
Miguel A
MA
García-Gimeno
María A
MA
Osada
Jesús
J
D000284:Administration, Oral; D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood* / Q000235:genetics; D001628:Beverages; D015415:Biomarkers / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D003545:Cysteine / Q000008:administration & dosage / Q000097:blood*; D004195:Disease Models, Animal; D005998:Glycine / Q000008:administration & dosage; D006710:Homocysteine / Q000097:blood*; D006712:Homocystinuria / Q000097:blood* / Q000235:genetics; D020138:Hyperhomocysteinemia / Q000097:blood* / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D013030:Spain; D014280:Triglycerides / Q000097:blood
D016632:Apolipoprotein A-I; D015415:Biomarkers; D001786:Blood Glucose; D008076:Cholesterol, HDL; D012333:RNA, Messenger; D014280:Triglycerides; D006710:Homocysteine; D003545:Cysteine; D005998:Glycine