Mechanism of Activation and Functional Significance of the Lipolysis-Stimulated Receptor. Evidence for a Role as Chylomicron Remnant Receptor

Mann, Christopher; Khallou, J.; Chevreuil, Olivier; Troussard, Armelle; Guermani, L.; Launay, Karine; Delplanque, Bernadette; Yen, Frances T.; Bihain, Bernard E.

doi:10.1021/bi00033a014

Cited by 40 publications

(67 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is generally accepted, however, that for the initial liver recognition of remnants, the so-called "capture step," additional systems are needed. The initial sequestration step was suggested to involve heparan sulfate proteoglycans (5,12), the lipolysis-stimulated receptor (13)(14)(15), a TG-rich lipoprotein receptor (16,17), the asialoglycoprotein receptor (18), LPL (19), and/or hepatic lipase (20), while we also provided evidence for a specific remnant receptor (21)(22)(23) to function as an initial recognition site for remnants. However, the removal pathways of chylomicrons and their remnants remain complex, and the precise mechanism of recognition is still unclear and under debate (1-3).…”

mentioning

confidence: 56%

Scavenger Receptor BI Plays a Role in Facilitating Chylomicron Metabolism

Out¹,

Kruijt²,

Rensen³

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

The function of scavenger receptor class B type I (SR-BI) in mediating the selective uptake of high density lipoprotein (HDL) cholesterol esters is well established. However, the potential role of SR-BI in chylomicron and chylomicron remnant metabolism is largely unknown. In the present investigation, we report that the cell association of 160 nm-sized triglyceride-rich chylomicronlike emulsion particles to freshly isolated hepatocytes from SR-BI-deficient mice is greatly reduced (>70%), as compared with wild-type littermate mice. Competition experiments show that the association of emulsion particles with isolated hepatocytes is efficiently competed for (>70%) by the well established SR-BI ligands, HDL and oxidized low density lipoprotein (LDL), whereas LDL is ineffective. Upon injection into SR-BI-deficient mice the hepatic association of emulsion particles is markedly decreased (ϳ80%) as compared with wild-type mice. The relevance of these findings for in vivo chylomicron (remnant) metabolism was further evaluated by studying the effect of SR-BI deficiency on the intragastric fat load-induced postprandial triglyceride response. The postprandial triglyceride response is 2-fold higher in SR-BI-deficient mice as compared with wild-type littermates (area-under-the-curve 39.6 ؎ 1.2 versus 21.1 ؎ 3.6; p < 0.005), with a 4-fold increased accumulation of chylomicron (remnant)-associated triglycerides in plasma at 6 h after intragastric fat load. We conclude that SR-BI is important in facilitating chylomicron (remnant) metabolism and might function as an initial recognition site for chylomicron remnants whereby the subsequent internalization can be exerted by additional receptor systems like the LDL receptor and LDL receptor-related protein. Chylomicrons are triglyceride (TG)1 -rich lipoproteins that transport dietary lipids from the intestine to the liver. Upon entering the circulation, chylomicrons are converted to remnants by the TG-hydrolyzing action of lipoprotein lipase (LPL) and the acquisition of apolipoproteins (apo) such as apoE. Chylomicron remnants are subsequently taken up by the liver by an apoE-mediated process (reviewed in Refs. 1-3). The essential role of apoE in remnant clearance was indicated by the accumulation of remnants in apoE-deficient mice (4). It has been suggested that several apoE-dependent recognition sites contribute to the removal of remnants, including the low-density lipoprotein (apoB and -E) receptor (LDLr) (4 -9), and the LDLr-related protein/␣ 2 -macroglobulin receptor (LRP) (8, 10, 11). It is generally accepted, however, that for the initial liver recognition of remnants, the so-called "capture step," additional systems are needed. The initial sequestration step was suggested to involve heparan sulfate proteoglycans (5, 12), the lipolysis-stimulated receptor (13-15), a TG-rich lipoprotein receptor (16, 17), the asialoglycoprotein receptor (18), LPL (19), and/or hepatic lipase (20), while we also provided evidence for a specific remnant receptor (21-23) to function as an initial re...

show abstract

mentioning

confidence: 56%

Scavenger Receptor BI Plays a Role in Facilitating Chylomicron Metabolism

Out¹,

Kruijt²,

Rensen³

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Of particular relevance to our study, Mann et al (25) reported that, compared with apoC-III 1 or apoC-III 0 , apoC-III 2 is a less effective inhibitor of VLDL uptake by the hepatic LSR. The LSR has been proposed as a rate-limiting factor for the clearance of triglycerides during the postprandial period (41,42). LSR heterozygous mice display increased postprandial triglyceride levels, decreased clearance of lipid particles, and increased levels of proatherogenic lipoproteins following a Western diet (35).…”

Section: Discussionmentioning

confidence: 99%

Disialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetes

Koška

Yassine

Trenchevska

et al. 2016

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

“…Genes lying at the 10 Mb region in humans that encompasses the point of maximum linkage evidence in baboons (HSA19q12-q13.12) include at least one with potential effects on LDL catabolism. LSR/LISCH7, the lipolysis-stimulated lipoprotein receptor, codes for a receptor that is differentially stimulated by free fatty acids of different chain lengths and is able to bind apoB-and apoE-containing lipoproteins (41). Furthermore, LSR is hypothesized to be an alternate pathway of LDL clearance in the liver separate from the LDLR or the LDL-receptor related protein (LRP) pathways (42).…”

Section: Discussionmentioning

confidence: 99%

Genotype-by-diet effects on co-variation in Lp-PLA2 activity and LDL-cholesterol concentration in baboons fed an atherogenic diet

Vinson

Mahaney

Diego

et al. 2008

Journal of Lipid Research

View full text Add to dashboard Cite

Both lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) activity, a biomarker of inflammation, and concentration of its primary associated lipoprotein, LDL, are correlated with adverse coronary outcomes. We previously reported a quantitative trait locus (QTL) corresponding to HSA2p24.3-p23.2 with pleiotropic effects on Lp-PLA 2 activity and LDL-cholesterol (LDL-C) concentration in baboons fed a basal diet. Here, our goal was to locate pleiotropic QTLs influencing both traits in the same baboons fed a highcholesterol, high-fat (HCHF) diet, and to assess whether shared genetic effects on these traits differ between diets. We assayed Lp-PLA 2 activity and LDL-C concentration in 683 baboons fed the HCHF diet. We used a bivariate maximum likelihood-based variance components approach in whole-genome linkage screens to locate a QTL [logarithm of odds (LOD) 5 3.13, genome-wide P 5 0.019] corresponding to HSA19q12-q13.2 with pleiotropic effects on Lp-PLA 2 activity and LDL-C levels in the HCHF diet. We additionally found significant evidence of genetic variance in response to diet for Lp-PLA 2 activity (P 5 0.0017) and for LDL-C concentration (P 5 0.00001), revealing a contribution of genotypeby-diet interaction to covariation in these two traits. We conclude that the pleiotropic QTLs detected at 2p24.3-p23.2 and 19q12-q13.2 on the basal and HCHF diets, respectively, exert diet-specific effects on covariation in Lp-PLA 2 activity and LDL-C

show abstract

Mechanism of Activation and Functional Significance of the Lipolysis-Stimulated Receptor. Evidence for a Role as Chylomicron Remnant Receptor

Cited by 40 publications

References 35 publications

Scavenger Receptor BI Plays a Role in Facilitating Chylomicron Metabolism

Scavenger Receptor BI Plays a Role in Facilitating Chylomicron Metabolism

Disialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetes

Genotype-by-diet effects on co-variation in Lp-PLA2 activity and LDL-cholesterol concentration in baboons fed an atherogenic diet

Contact Info

Product

Resources

About