[Liver mechanisms for the elimination of lipoproteins of intestinal origin].
This article critically examines the concept of the putative chylomicron remnant receptor (CMR). The molecular nature of this second lipoprotein receptor remains disputed. Indeed, two proteins, the low density lipoprotein receptor-related protein (LRP) and the lipolysis stimulated receptor (LSR) have been proposed as candidates for this function. The LRP bears significant structural homology with the LDL receptor and mediates the internalisation of beta-VLDL enriched with apo E. In addition, LRP binds several ligands not related to the lipoprotein system. Thus, LRP's contribution to the clearance of CMR has been questioned. The precise biochemical structure of LSR remains unclear. However, a series of observations support the hypothesis that LSR is the CMR receptor. LSR, which is activated by free fatty acis (FFA), the products of lipolysis, is present in primary cultures of rat hepatocytes. It displays the highest affinity for triglyceride-rich lipoproteins and is inhibited by lactoferrin. The existence of a strong inverse correlation in rats between the apparent number of hepatic LSR and the plasma triglyceride concentration measured in the post-prandial state, indicate that LSR represents a rate-limiting step for the removal of triglyceride-rich lipoproteins. Moreover, the ability of MAXEPA to enhance the expression of LSR in parallel with its well documented hypotriglyceridemic effect indicates that, contrary to popular belief, the putative CMR receptor represents a target for pharmacological management of hyperlipidemia.
Khallou
J
J
INSERM U391, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes I.
Troussard
A A
AA
Masson
M
M
Delplanque
B
B
Mann
C J
CJ
André
P
P
Yen
F T
FT
Bihain
B E
BE
D002914:Chylomicrons / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008657:Metabolic Clearance Rate; D011971:Receptors, Immunologic / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism
D002914:Chylomicrons; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; D011973:Receptors, LDL; C085992:lipolysis-stimulated receptor
Mécanismes hépatiques d'élimination des lipoprotéines d'origine intestinale.