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.