Mechanisms
Diet-induced hypercholesterolemia raises plasma LTIP mass 2.5-fold while suppressing its hepatic mRNA, diverging from CETP's response in hamsters and rabbits (J Lipid Res 2008)
Original title: Molecular cloning of hamster lipid transfer inhibitor protein (apolipoprotein F) and regulation of its expression by hyperlipidemia
Lipid transfer inhibitor protein (LTIP) regulates cholesteryl ester transfer protein (CETP) function, but factors controlling plasma LTIP levels are poorly understood, though human plasma LTIP is known to rise in hypercholesterolemia. The authors cloned hamster LTIP, finding its hepatic-exclusive mRNA encodes a protein 69% homologous to human LTIP, with an isoelectric point of 4.15 and Mr of approximately 16.4 kDa. Feeding hamsters hydrogenated coconut oil, cholesterol, or both raised plasma LTIP mass up to 2.5-fold, correlating strongly with plasma cholesterol, and similarly raised CETP mass. In contrast, these diets reduced LTIP hepatic mRNA by more than 50%, while CETP mRNA increased; similar divergent results occurred in cholesterol-fed rabbits. CETP and LTIP thus respond distinctly to dietary lipids.
Original abstract
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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.