Correlating Metabolism of Plasma and Tissue Cholesterol With That of Plasma-Lipoproteins

Sodhi, H. S.; Kudchodkar, Bhalchandra J.

doi:10.1016/s0140-6736(73)90329-2

Cited by 63 publications

(15 citation statements)

References 38 publications

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“…The resulting higher activity of this enzyme would account for the increase in cholesterol synthesis in hypertriglyceridemia. Our data predict that when plasma triglyceride levels are reduced, both abnormalities should be corrected and indeed reduction in cholesterol synthesis has been reported in HTG patients treated with clofibrate (48,49).…”

Section: Discussionsupporting

confidence: 69%

“…In other studies, total body cholesterol synthesis was reported to be considerably higher in patients with hypertriglyceridemia as compared with normals and patients with hypercholesterolemia (47)(48)(49)(50). The increased fractional catabolic rate of LDL-apo B could be related to the presently described finding that the HTG-LDL particle delivers less cholesterol to cells than N-LDL and therefore is less effective in the down regulation of the LDL receptor and in inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase.…”

Section: Discussionmentioning

confidence: 80%

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Defective metabolism of hypertriglyceridemic low density lipoprotein in cultured human skin fibroblasts. Normalization with bezafibrate therapy.

Kleinman¹,

Eisenberg²,

Oschry³

et al. 1985

J. Clin. Invest.

125

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The metabolism of hypertriglyceridemic low density lipoprotein (HTG-LDL) was investigated in upregulated cultured human skin fibroblasts. Low density lipoprotein (LDL) was isolated by zonal centrifugation from the plasma of seven HTG subjects, before and 2 wk after the initiation of bezafibrate (BZ) therapy. HTG-LDL is a cholesterol-poor, triglyceride-rich lipoprotein of smaller diameter than BZ-LDL or normal LDL (N-LDL). Binding, cell association, and proteolytic degradation of HTG-LDL were compared with that of BZ-LDL and N-LDL and were found to be significantly lower by a paired t test analysis (P < 0.001). After 6 h preincubation with unlabeled HTG-LDL, the incorporation of [14Clacetate to sterols was significantly higher than with BZ-LDL or N-LDL (577±43.7; 330±41.5; 262±47, mean±SE, picomoles sterols per milligram cell protein per 2 h, respectively; P < 0.001 by paired t test).To determine the effectiveness of HTG-LDL and BZ-LDL on the down-regulation of LDL receptor activity, up-regulated cells were incubated for 48 h with HTG-LDL and BZ-LDL. LDL receptor activity was significantly higher after preincubation with HTG-LDL compared with BZ-LDL, and the rates of sterol synthesis were similarly increased. These results demonstrate that HTG-LDL does not down-regulate the LDL receptor activity as efficiently as BZ-LDL and that its cholesterol content is not enough to adequately suppress cellular sterol synthesis.Significant correlation between LDL composition and cholesterol synthesis by cultured cells was found with all LDL preparations over a wide range of cholesteryl ester to protein ratio (0.8-2.2). This correlation indicates that the compositional and structural abnormalities of HTG-LDL, and especially the low cholesterol content of the lipoprotein, alter LDL metabolism and cellular cholesterol formation.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 80%

Defective metabolism of hypertriglyceridemic low density lipoprotein in cultured human skin fibroblasts. Normalization with bezafibrate therapy.

Kleinman¹,

Eisenberg²,

Oschry³

et al. 1985

J. Clin. Invest.

125

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“…Decreaszd absorption of unlabeled cholesterol would be expected to cause a flattened slope, and this was not observed. This would seem to rule out the possibility that the entire increase in fecal Likewise, if cholesterol more richly labeled in tissues than in plasma were mobilized into the plasma compartment, a flattening of slope would be expected (46). But this change would be hidden if simultaneously there were increased synthesis secondary to decreased absorption.…”

Section: Mechanism Of Decrease In Cholesterol Absorptionmentioning

confidence: 99%

Effects of neomycin on absorption, synthesis, and/or flux of cholesterol in man.

Sedaghat¹,

Samuel²,

Crouse³

et al. 1975

J. Clin. Invest.

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A B S T R A C T The mode of action of the hypocholesteremic drug neomycin (2 g/day) was studied in four patients. All showed a significant reduction in plasma cholesterol concentrations (mean 25%, range (1), and since then it has been demonstrated that a few other antibacterial drugs have similar properties. Of these kanamycin (2) and paromomycin (3) are similar in structure to neomycin, but chlortetracycline (2), chloramphenicol (4), and para-aminosalicylic acid (2) have markedly different molecular conDr. Sedaghat's present address is:

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“…Obesity is often associated with raised serum triglycerides, and in extreme cases is linked with excessive production of cholesterol (Miettinen, 1971) and uniform cholesterol oversaturation of bile (1 30 ± 0-7 mol/dl) compared with controls (6-6 ± 0-5 mol/dl) (Freeman et al, 1975). As serum triglycerides parallel total body production of cholesterol (Sodhi and Kudchodkar, 1973), whereas serum cholesterol levels do not (Miettinen, 1971;Sodhi and Kudchodkar, 1973), a logical connection may be seen between enhanced synthesis and enhanced excretion by the main pathway. Differences in weight were not observed between our patients with or without hypertriglyceridaemia, so this was not a factor.…”

Section: Discussionmentioning

confidence: 99%

Effect of prolonged feeding with chenodeoxycholic acid on bile in patients with and without gallstones.

Bateson¹,

Ross²,

Murison³

et al. 1977

Gut

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SUMMARY Nineteen patients who received chenodeoxycholic acid 750 mg/day for six months had duodenal bile aspirated before and after treatment. In five patients with hypertriglyceridaemia but no gallstones cholesterol saturation was reversed in every case, the mean cholesterol saturation index (SI ± standard deviation) changing from 1 38 ± 0-31 to 0-68 ± 0-06 (P < 0.005). In 14 patients with gallstones there was also an improvement in bile cholesterol content, but this was not sufficient to produce mean unsaturation, saturation index changing from 155 ± 0-52 to 113 ± 0 43 (P < 0 05). Only seven of 14 patients with gallstone achieved cholesterol unsaturation. In four patients with hypertriglyceridaemia and gallstones, mean unsaturation was produced and the saturation index changed from 1 70 0 45 to 0-86 ± 0 47 (P < 0 05). When all nine patients with hypertriglyceridaemia were grouped, the mean saturation index fell from 1 52 ± 0 40 to 0-76 ± 0 30 after therapy (P < 0-001). In contrast the 10 patients without hypertriglyceridaemia showed no significant fall in saturation index which was 150 ± 0 54 before and 1 24 ± 0 40 after therapy. The ability of chenodeoxycholic acid feeding to improve bile saturation with cholesterol correlated with the presence of hypertriglyceridaemia whether or not gallstones were present. It did not correlate with gallstone dissolution or body weight.

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Correlating Metabolism of Plasma and Tissue Cholesterol With That of Plasma-Lipoproteins

Cited by 63 publications

References 38 publications

Defective metabolism of hypertriglyceridemic low density lipoprotein in cultured human skin fibroblasts. Normalization with bezafibrate therapy.

Defective metabolism of hypertriglyceridemic low density lipoprotein in cultured human skin fibroblasts. Normalization with bezafibrate therapy.

Effects of neomycin on absorption, synthesis, and/or flux of cholesterol in man.

Effect of prolonged feeding with chenodeoxycholic acid on bile in patients with and without gallstones.

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