Upregulation of liver VLDL receptor and FAT/CD36 expression in LDLR-/- apoB100/100 mice fed trans-10,cis-12 conjugated linoleic acid.
This study explores the mechanisms responsible for the fatty liver setup in mice fed trans-10,cis-12 conjugated linoleic acid (t10c12 CLA), hypothesizing that an induction of low density lipoprotein receptor (LDLR) expression is associated with lipid accumulation. To this end, the effects of t10c12 CLA treatment on lipid parameters, serum lipoproteins, and expression of liver lipid receptors were measured in LDLR(-/-) apoB(100/100) mice as a model of human familial hypercholesterolemia itself depleted of LDLR. Mice were fed t10c12 CLA over 2 or 4 weeks. We first observed that the treatment induced liver steatosis, even in the absence of LDLR. Mice treated for 2 weeks exhibited hypertriglyceridemia with high levels of VLDL and HDL, whereas a 4 week treatment inversely induced a reduction of serum triglycerides (TGs), essentially through a decrease in VLDL levels. In the absence of LDLR, the mRNA levels of other proteins, such as VLDL receptor, lipoprotein lipase, and fatty acid translocase, usually not expressed in the liver, were upregulated, suggesting their involvement in the steatosis setup and lipoprotein clearance. The data also suggest that the TG-lowering effect induced by t10c12 CLA treatment was attributable to both the reduction of circulating free fatty acids in response to the severe lipoatrophy and the high capacity of liver to clear off plasma lipids.
Degrace
Pascal
P
Unité Propre de Recherche de l'Enseignement Supérieur, Lipides et Nutrition EA2422, Faculté des Sciences Gabriel, Université de Bourgogne, 21000 Dijon, France. pascal.degrace@u-bourgogne.fr
Moindrot
Bastien
B
Mohamed
Ismaël
I
Gresti
Joseph
J
Du
Zhen-Yu
ZY
Chardigny
Jean-Michel
JM
Sébédio
Jean-Louis
JL
Clouet
Pierre
P
D000818:Animals; D053299:Apolipoprotein B-100 / Q000235:genetics / Q000378:metabolism*; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D004041:Dietary Fats / Q000008:administration & dosage; D005227:Fatty Acids / Q000378:metabolism; D044243:Linoleic Acids, Conjugated / Q000008:administration & dosage*; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008066:Lipolysis; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D053299:Apolipoprotein B-100; D018955:CD36 Antigens; D004041:Dietary Fats; D005227:Fatty Acids; D044243:Linoleic Acids, Conjugated; D008055:Lipids; D012333:RNA, Messenger; D011973:Receptors, LDL; C036053:VLDL receptor; C496197:trans-10,cis-12-conjugated linoleic acid