Premium
Lactoferrin and its hydrolysate bind directly to the oleate‐activated form of the lipolysis stimulated lipoprotein receptor
Author(s) -
Ahmad Nazir,
Girardet JeanMichel,
Akbar Samina,
Lanhers MarieClaire,
Paris Cédric,
Yen Frances T.,
Corbier Catherine
Publication year - 2012
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12026
Subject(s) - chylomicron , lactoferrin , postprandial , lipolysis , lipoprotein , triglyceride , chemistry , receptor , biochemistry , endocrinology , medicine , biology , cholesterol , adipose tissue , very low density lipoprotein , insulin
The hepatic removal of triglyceride‐rich chylomicrons during the postprandial phase represents an important step towards determining the bioavailability of dietary lipids amongst the peripheral tissues. Indeed, elevated postprandial lipemia is often associated with obesity and increased risk of coronary heart disease. The milk protein, lactoferrin, has been shown to inhibit hepatic chylomicron remnant removal by the liver, resulting in increased postprandial lipemia. Despite numerous studies on potential targets for lactoferrin, the molecular mechanisms underlying the effect of lactoferrin remain unclear. We recently demonstrated that the lipolysis stimulated lipoprotein receptor ( LSR ) contributes to the removal of triglyceride‐rich lipoproteins during the postprandial phase. Here, we report that while lactoferrin does not have any significant effect on LSR protein levels in mouse Hepa1–6 cells, this protein colocalizes with LSR in cells but only in the presence of oleate, which is needed to obtain LSR in its active form as lipoprotein receptor. Ligand blotting using purified LSR revealed that lactoferrin binds directly to the receptor in the presence of oleate and prevents the binding of triglyceride‐rich lipoproteins. Both C ‐ and N ‐lobes of lactoferrin as well as a mixture of peptides derived from its hydrolysis retained the ability to bind LSR in its active form. We propose then that the elevated postprandial lipemia observed upon lactoferrin treatment in vivo is mediated in part by its direct interaction with free fatty acid activated LSR , thus preventing clearance of chylomicrons and their remnants through the LSR pathway. Structured digital abstract • Lsr and Lsr bind by comigration in gel electrophoresis ( View interaction ) • Lsr binds to Lf by filter binding ( View interaction ) • Lf and Lsr colocalize by fluorescence microscopy ( View interaction ) • Lsr physically interacts with VLDL by filter binding ( View interaction )