Molecular cloning of hamster lipid transfer inhibitor protein (apolipoprotein F) and regulation of its expression by hyperlipidemia.
Lipid transfer inhibitor protein (LTIP) is a regulator of cholesteryl ester transfer protein (CETP) function. Factors affecting plasma LTIP levels are poorly understood. In humans, plasma LTIP is elevated in hypercholesterolemia. To define possible mechanisms by which hyperlipidemia modifies LTIP, we investigated the effects of hypercholesterolemic diets on plasma LTIP and mRNA levels in experimental animals. The hamster, which naturally expresses CETP, was shown to express LTIP. Hamster LTIP mRNA, exclusively detected in the liver, defined a predicted LTIP protein that is 69% homologous to human, with an isoelectric point of 4.15 and Mr = approximately 16.4 kDa. Hyperlipidemia induced by feeding hydrogenated coconut oil, cholesterol, or both lipids increased plasma LTIP mass up to 2.5-fold, with LTIP mass correlating strongly with plasma cholesterol levels. CETP mass was similarly affected by these diets. In contrast, these diets reduced LTIP hepatic mRNA levels by >50%, whereas CETP mRNA was increased. Similar results for both CETP and LTIP were also observed in cholesterol-fed rabbits. In conclusion, we report in hamster and rabbit that dietary lipids regulate LTIP. Diet-induced hypercholesterolemia markedly increased plasma LTIP mass while concomitantly depressing LTIP gene expression. CETP and LTIP have distinct responses to dietary lipids.
Izem
Lahoucine
L
Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Morton
Richard E
RE
D000595:Amino Acid Sequence; D000818:Animals; D001053:Apolipoproteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D003001:Cloning, Molecular; D006224:Cricetinae; D017931:DNA Primers / Q000235:genetics; D004036:Diet, Atherogenic; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus / Q000235:genetics; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D015533:Transcriptional Activation
D001053:Apolipoproteins; D053480:Cholesterol Ester Transfer Proteins; D002791:Cholesterol, Dietary; D017931:DNA Primers; D012333:RNA, Messenger; C036321:apolipoprotein F