Trans-10, cis-12- and cis-9, trans-11-conjugated linoleic acid isomers selectively modify HDL-apolipoprotein composition in apolipoprotein E knockout mice.
Trans-10, cis-12-conjugated linoleic acid (CLA)-enriched diets promote atherosclerosis in mice despite increasing blood concentrations of HDL cholesterol. This suggests that under these conditions, the HDL apolipoproteins (apo) produced are abnormal. To test this hypothesis, apoE-deficient mice were fed a Western-type diet enriched with linoleic acid (control), cis-9, trans-11-CLA or trans-10, cis-12-CLA (1.0% wt/wt) for 12 wk, and the effects on HDL metabolism and apoC-III levels recorded. Compared with the control and cis-9, trans-11-CLA mice, those fed the trans-10, cis-12-CLA diet had significantly higher HDL cholesterol concentrations, and had a higher incidence of hypertriglyceridemia and hepatic steatosis. Plasma apoA-I and paraoxonase concentrations were significantly lower in the trans-10, cis-12-CLA group than in the cis-9, trans-11-CLA group. These reductions were associated with decreased hepatic expression of these proteins and a shift toward lipid-poor apolipoprotein particles. The plasma apoA-II concentration increased with its corresponding mRNA concentration in the liver, and was preferentially bound to HDL in the trans-10, cis-12-CLA mice, thus explaining the increased HDL cholesterol concentrations in this group. Significant, positive associations were found between apoA-II and C-III (r=0.883, P<0.001) and between apoA-II and atherosclerosis (r=0.68, P<0.001). These results indicate that trans-10, cis-12-CLA intake modifies HDL to form a proatherogenic apoA-II containing particle and promotes phenotypic changes compatible with metabolic syndrome. Cis-9, trans-11-CLA does not promote this detrimental effect.
Arbonés-Mainar
José M
JM
Departmento de Bioquímica y Biología Molecular y Celular, Trinity College, Dublin, Ireland.
Navarro
María A
MA
Acín
Sergio
S
Guzmán
Mario A
MA
Arnal
Carmen
C
Surra
Joaquín C
JC
Carnicer
Ricardo
R
Roche
Helen M
HM
Osada
Jesús
J
D000818:Animals; D001053:Apolipoproteins / Q000097:blood* / Q000145:classification; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D043303:Aryldialkylphosphatase / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D005786:Gene Expression Regulation / Q000187:drug effects; D007536:Isomerism; D044243:Linoleic Acids, Conjugated / Q000737:chemistry* / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout
D001053:Apolipoproteins; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D044243:Linoleic Acids, Conjugated; D043303:Aryldialkylphosphatase