PROJECT SUMMARY
The low-density lipoprotein receptor (LDLR) is a widely expressed protein known mostly for its role in hepatic
uptake and clearance of LDL cholesterol. Like cholesterol, carotenoids such as ß-carotene and lutein are
transported in LDL particles due to their hydrophobic nature. There remains, however, unknowns about the
metabolic fate of carotenoids found in lipoproteins, as well as the function of LDLR in these processes. In
particular, LDLR is known to mediate transintestinal cholesterol excretion, which is known to account for up to
35% of cholesterol excretion in humans. Whether carotenoids are also eliminated through this process is
unknown. Carotenoids are primarily stored in the liver, but surprisingly, several knowledge gaps exist in the
hepatic metabolism of carotenoids, including if LDLR mediates the hepatic uptake of carotenoids, or if
carotenoids, like cholesterol, modify the characteristics of secreted in VLDL particles. Therefore, the overarching
objective of this proposal is to characterize the role of LDLR in carotenoid excretion and hepatic uptake, as well
as examine the incorporation of carotenoids into VLDL particles and how VLDL characteristics are consequently
altered. We hypothesize that LDLR mediates transintestinal carotenoid excretion and contributes to hepatic
carotenoid uptake. We also hypothesize that hepatic carotenoids are incorporated into newly-synthesized VLDL
and modify their size and lipid content. To test these hypotheses, we propose three objectives that will
characterize the involvement of LDLR in carotenoid uptake and excretion, as well as hepatic participation in
carotenoid distribution. These studies have the potential to reveal critical pathways in carotenoid transport and
elimination in humans.