Lactoferrin and its hydrolysate bind directly to the oleate-activated form of the lipolysis stimulated lipoprotein receptor

Authors

  • Nazir Ahmad,

    1. Université de Lorraine, Unité de Recherche Animal et Fonctionnalités des Produits Animaux, Vandœuvre-lès-Nancy Cedex, France
    2. Université de Lorraine, Lipidomix, Vandœuvre-lès-Nancy Cedex, France
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  • Jean-Michel Girardet,

    1. Université de Lorraine, Unité de Recherche Animal et Fonctionnalités des Produits Animaux, Vandœuvre-lès-Nancy Cedex, France
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  • Samina Akbar,

    1. Université de Lorraine, Lipidomix, Vandœuvre-lès-Nancy Cedex, France
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  • Marie-Claire Lanhers,

    1. Université de Lorraine, Lipidomix, Vandœuvre-lès-Nancy Cedex, France
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  • Cédric Paris,

    1. Université de Lorraine, Plateau Analyse Structurale et Métabolomique, Vandœuvre-lès-Nancy Cedex, France
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  • Frances T. Yen,

    Corresponding author
    1. Université de Lorraine, Lipidomix, Vandœuvre-lès-Nancy Cedex, France
    • Université de Lorraine, Unité de Recherche Animal et Fonctionnalités des Produits Animaux, Vandœuvre-lès-Nancy Cedex, France
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  • Catherine Corbier

    Corresponding author
    • Université de Lorraine, Unité de Recherche Animal et Fonctionnalités des Produits Animaux, Vandœuvre-lès-Nancy Cedex, France
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Correspondence

C. Corbier, Université de Lorraine, Unité de Recherche Animal et Fonctionnalités des Produits Animaux (UR AFPA), Unité Sous Contrat INRA 340, Vandœuvre-lès-Nancy Cedex F-54506, France

Fax: +33 (0)3 83 59 61 81

Tel: +33 (0)3 83 59 61 84

E-mail: catherine.corbier@univ-lorraine.fr

F. Yen, Université de Lorraine, Lipidomix, EA 4422, Vandœuvre-lès-Nancy Cedex F-54500, France

Fax: +33 (0)3 83 59 61 81

Tel: +33 (0)3 83 59 61 84

E-mail: frances.yen-potin@univ-lorraine.fr

Abstract

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)

Ancillary