The relationship between HDL-, LDL-, liposomes-free cholesterol, biliary cholesterol and bile salts in the rat

Esnault-Dupuy, Christine; Chanussot, F.; Lafont, Huguette; Chabert, C.; Hauton, J. C.

doi:10.1016/0300-9084(87)90270-7

Cited by 18 publications

(12 citation statements)

References 27 publications

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“…Finally, trapping of the mobilized cholesterol in LUVs, which deliver cholesterol to the liver without disturbing genes for cholesterol homeostasis, 41 is far preferable to accelerated HDLmediated sterol delivery to the liver, which can be associated with harmful side effects. 54 For example, although tracer studies [55][56][57][58] suggest that HDL cholesterol can appear in bile, studies of mass flux indicate that the intravenous administration of a cholesterol-rich HDL fraction into rats results in a stimulation of hepatic acyl-CoA:cholesterol acyl transferase and enhanced secretion of cholesterol-rich VLDL, 54 a particle that could potentially be proatherogenic. LUVs, acting with endogenous HDL, may be the preferred therapeutic method to enhance RCT in vivo.…”

Section: Discussionmentioning

confidence: 99%

Remodeling and Shuttling

Rodrigueza

Williams

Rothblat

et al. 1997

ATVB

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In normal physiology, cells are exposed to cholesterol acceptors of different sizes simultaneously. The current study examined the possible interactions between two different classes of acceptors, one large (large unilamellar phospholipid vesicles, LUVs) and one small (HDL or other small acceptors), added separately or in combination to Fu5AH rat hepatoma cells. During a 24-hour incubation, LUVs of palmitoyl-oleoyl phosphatidylcholine at 1 mg phospholipid (PL) per milliliter extracted ≈20% of cellular unesterified cholesterol (UC) label and mass in a slow, continuous fashion (half-time [t½] for UC efflux was ≈50 hours) and human HDL 3 at 25 μg PL per milliliter extracted ≈15% cellular UC label with no change in cellular cholesterol mass (t½ of ≈8 hours). In contrast, the combination of LUVs and HDL 3 extracted over 90% of UC label (t½ of ≈4 hours) and ≈50% of the UC mass, indicating synergy. To explain this synergy, specific particle interactions were examined, namely, remodeling, in which the two acceptors alter each other's composition and thus the ability to mobilize cellular cholesterol, and shuttling, in which the small acceptor ferries cholesterol from cells to the large acceptor. To examine remodeling, LUVs and HDL were coincubated and reisolated before application to cells. This HDL became UC depleted, PL enriched, and lost a small amount of apolipoprotein A-I. Compared with equivalent numbers of control HDL particles, remodeled HDL caused faster efflux (t½ ≈4 hours) and exhibited a greater capacity to sequester cellular cholesterol over 24 hours (≈38% versus ≈15% for control HDL), consistent with their enrichment in PL. Remodeled LUVs still extracted ≈20% of cellular UC. Thus, remodeling accounted for some but not all of the synergy between LUVs and HDL. To examine shuttling, several approaches were used. First, reisolation of particles after an 8-hour exposure to cells revealed that HDL contained very little of the cellular UC label. The label was found almost entirely with the LUVs, suggesting that LUVs continuously stripped the HDL of cellular UC. Second, bidirectional flux studies demonstrated that LUVs blocked the influx of HDL UC label into cells, while the rate of efflux of cellular UC was maintained. These kinetic effects explained the massive net loss of cellular UC to LUVs with HDL. Third, cyclodextrin, an artificial small acceptor that does not acquire PL and hence does not become remodeled, exhibitedCorrespondence to Dr Michael C. Phillips, Department of Biochemistry, Medical College of Pennsylvania and Hahnemann University, 2900 Queen Ln, Philadelphia, PA 19129. Portions of this work were published in abstract form in Abstracts Submitted to the Council on Arteriosclerosis for the 68th Scientific Sesssions of the American Heart Association. 1995:54. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript substantial synergy with LUVs, supporting shuttling. Thus, the presence of large and small acceptors together can overcome intrinsic deficiencies in...

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Section: Discussionmentioning

confidence: 99%

Remodeling and Shuttling

Rodrigueza

Williams

Rothblat

et al. 1997

ATVB

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“…C vs. S; '2 p < 0.01, C vs. PU; r2 p < 0.01, S vs. PU; h2 p < 0.001, C vs. PU; '2 p < 0.001, S vs. PU. 1 From results previously obtained [9]. …”

Section: Comparison O F the Fate O F The 4c Free Cholesterol Originamentioning

confidence: 86%

“…In a previous paper we have investigated the exchange of cholesterol between HDL, LDL and erythrocytes [9]. It was found that the l4C-cholesterol presented a lesser extent of esterification in all lipoproteins.…”

Section: Discussionmentioning

confidence: 99%

“…In the second experiment (3 rats -S, 3 rats -PU after l4C-HDL injection and 4 rats -S, 3 rats -PU after MC-LDL injection) intravenous injections of HDL or LDL which had been labelled with l4C-FC made it possible to compare the fate of this ,4C-cholesterol with that previously studied in an experiment conducted with normal C diet [9]. (table I) Three diets (C, S and PU) were administered in a paste form ad libitum: two high-fat diets (28%) en riched with cholesterol (1.2%) and one control diet containing 6% lipids.…”

Section: Animalsmentioning

confidence: 99%

“…Serum lipoproteins (HDL, LDL) were then iso lated by sucrose density adjustment and flotation dur ing ultracentrifugations previously described [11], The labeling of the lipoproteins was performed fol lowing a technic of free l4C-cholesterol exchange for HDL and l4C-cholesterol liposomes incubated with LDL as previously described [9], In our experimental conditions, the final label of the HDL represented 60-65% of the l4C-cholesterol dose present in the nonpurified HDL fraction. The radio active LDL label represented about 50% of that contained on 14C-liposomes.…”

Section: Preparation O F L4c-ldl and Nc-hdlmentioning

confidence: 99%

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Metabolism of Low- and High-Density-Lipoprotein-Free Cholesterol in Rats Fed High-Fat Diets

Chanussot¹,

Esnault-Dupuy²,

Martigne³

et al. 1988

Ann Nutr Metab

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The regulating process of cholesterol in the liver was studied in relation to its exogenous contribution in the rats fed high-fat (28%) high-cholesterol (1.2%) diets rich in saturated (S) fat (lard) or polyunsaturated (PU) fat (corn oil). Accordingly, the fate of ¹⁴C free cholesterol originating from high- or low-density lipoproteins (LDL) was examined in the biliary, hepatic and plasmatic lipids, as well as the activity of two key enzymes in the metabolism of lipoproteins: lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT). The LPL activity increased in the S diet, in comparison to the PU diet or to a low fat (6 %) control (C) diet and the LCAT activity increased but not significantly in the PU diet. In bile the secretion of ¹⁴C-cholesterol and ¹⁴C-bile salts originating from ¹⁴C-cholesterol-HDL increased in the S diet compared to the PU diet and a C diet [previous results]. S and PU diets increased to the same extent the hepatic storage of ¹⁴C-esterified cholesterol originating from LDL, compared to the C diet. This cholesterol would contribute to a greater extent to the hepatic synthesis of the lipoproteins destined for the plasma in the case of the S diet than that of PU diet. These results may be explained by the adaptation of hepatic acyl cholesterol acyl transferase and cholesterolesterase to both high-fat-diet enzymes acting simultaneously on the two free and esterfied cholesterol compartments. It resulted in an important redistribution of the cholesterol of these two compartments between plasma, bile and liver.

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