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.
Highlights
Lipid transfer inhibitor protein (LTIP) is a regulator of cholesteryl ester transfer protein (CETP) function
We have proposed that the balance of CETP and LTIP activities is important in defining the flux of CETP substrates, cholesteryl ester, and triglyceride, between lipoproteins [5,6,7]
Most studies were performed in hamsters, where animals were fed diets enriched in saturated fat and/or cholesterol to assess acute (3 day) and chronic (30 day) effects of these lipids on plasma lipoproteins, LTIP levels, and LTIP gene expression
Summary
Lipid transfer inhibitor protein (LTIP) is a regulator of cholesteryl ester transfer protein (CETP) function. Supplementary key words rabbit cholesterol hydrogenated coconut oil Cholesteryl ester transfer protein (CETP) is an important regulator of lipoprotein composition, and its activity affects plasma lipoprotein levels [1,2,3]. Lipid transfer inhibitor protein (LTIP), known as apolipoprotein F (apoF), impacts CETP activity in a unique way compared with other factors that have been proposed to regulate CETP activity. In cholesterol-fed animals, increased plasma CETP levels are accompanied by marked increases in hepatic and extrahepatic CETP mRNA [12,13,14,15], but it is not known how cholesterol feeding affects plasma levels of LTIP or LTIP gene expression. Most studies were performed in hamsters, where animals were fed diets enriched in saturated fat and/or cholesterol to assess acute (3 day) and chronic (30 day) effects of these lipids on plasma lipoproteins, LTIP levels, and LTIP gene expression.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
