Cholesterol metabolism in hypercholesterolemia-resistant rabbits

Loose-Mitchell, David S.; Poorman, Julie A.; Smith, S. A.; Overturf, M. L.; Morrisett, Joel D.; Gotto, Antonio M.; Soma, Maurizio R.

doi:10.1016/0021-9150(91)90019-y

Cited by 12 publications

(5 citation statements)

References 31 publications

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“…In the liver, the main uptake organ for VLDL, LDL and lipid nanoparticles, the hyperlipidemia effect on uptake has been well documented (30)(31)(32). Nonetheless, it is interesting to point out that in the aortic arch, the main site of atherosclerotic plaque installation (33,34), and also in pancreatic, gonad, gallbladder, skin, and adipose tissue, the induction of hyperlipidemia did not diminish the uptake of the nanoparticle labels.…”

Section: Discussionmentioning

confidence: 92%

“…Because the LDL-like nanoparticles are removed by the LDL receptors (27), it is conceivable that in cholesterol-fed animals the competition for the receptors of the artificial nanoparticles with the natural lipoproteins is increased and thus the removal from the plasma, i.e., the uptake by the tissues, is diminished. Furthermore, cholesterol feeding down-regulates the lipoprotein uptake by the LDL receptors (30)(31)(32), which aggravates the competition for receptor binding and makes the internalization of the nanoparticles into the cells more difficult.…”

Section: Discussionmentioning

confidence: 99%

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Effect of a cholesterol-rich diet on the metabolism of the free and esterified cholesterol components of a nanoemulsion that resembles LDL in rabbits

Padoveze

Maniero

Oliveira

et al. 2009

Braz J Med Biol Res

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We have shown that the free cholesterol (FC) and the cholesteryl ester (CE) moieties of a nanoemulsion with lipidic structure resembling low-density lipoproteins show distinct metabolic fate in subjects and that this may be related to the presence of dyslipidemia and atherosclerosis. The question was raised whether induction of hyperlipidemia and atherosclerosis in rabbits would affect the metabolic behavior of the two cholesterol forms. Male New Zealand rabbits aged 4-5 months were allocated to a control group (N = 17) fed regular chow and to a 1% cholesterol-fed group (N = 13) during a 2-month period. Subsequently, the nanoemulsion labeled with 3 H-FC and 14 C-CE was injected intravenously for the determination of plasma kinetics and tissue uptake of the radioactive labels. In controls, FC and CE had similar plasma kinetics (fractional clearance rate, FCR = 0.234 ± 0.056 and 0.170 ± 0.038 h -1 , respectively; P = 0.065). In cholesterolfed rabbits, the clearance of both labels was delayed and, as a remarkable feature, FC-FCR (0.089 ± 0.033 h -1 ) was considerably greater than CE-FCR (0.046 ± 0.010 h -1 ; P = 0.026). In the liver, the major nanoemulsion uptake site, uptake of the labels was similar in control animals (FC = 0.2256 ± 0.1475 and CE = 0.2135 ± 0.1580%/g) but in cholesterol-fed animals FC uptake (0.0890 ± 0.0319%/g) was greater than CE uptake (0.0595 ± 0.0207%/g; P < 0.05). Therefore, whereas in controls, FC and CE have similar metabolism, the induction of dyslipidemia and atherosclerosis resulted in dissociation of the two forms of cholesterol.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Effect of a cholesterol-rich diet on the metabolism of the free and esterified cholesterol components of a nanoemulsion that resembles LDL in rabbits

Padoveze

Maniero

Oliveira

et al. 2009

Braz J Med Biol Res

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“…In the present study it was observed that the atherogenic diet increased the total cholesterol in both serum and tissues. It may be due to enhanced endogenous synthesis of cholesterol during high intake of fats (Mitchell et al, 1991;Ritu et al, 1996). Atherogenic diet also causes an increase of triglycerides in both serum and tissues.…”

Section: Discussionmentioning

confidence: 99%

Effect of an indigenous herbal compound preparation ‘Trikatu’ on the lipid profiles of atherogenic diet and standard diet fed Rattus norvegicus

Sivakumar

2004

Phytotherapy Research

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Combating heart disease is one of the challenging problems of biomedical science today. Towards this goal an indigenous preparation 'Trikatu' (a herbal combination containing Piper longum (fruit), Piper nigrum (fruit) and Zingiber officinale (rhizome) dry powder) was fed to normal and cholesterol fed male Rattus norvegicus to ascertain its efficacy as a hypolipidaemic agent. Its effects on body weight, blood and tissue (aortic, cardiac and hepatic) lipids--total, free and esterified cholesterol, low density lipoprotein(LDL) and high density lipoprotein(HDL) cholesterol, triglycerides and phospholipids--and the atherogenic index were measured. It was found that 'Trikatu' by virtue of its ability to reduce triglycerides and LDL cholesterol and to increase HDL cholesterol can reduce the risk of hyperlipidaemia and atherosclerosis. Hence 'Trikatu' can be used as a potent hypolipidaemic agent and it can reduce the atherosclerosis associated with a high fat diet.

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“…First, a genetic variant of the NZW rabbit strain that was relatively resistant to diet induced hypercholesterolemia also had an elevated level of C7AH expression (38). In addition, the susceptible rabbit strain, but not the resistant variant, showed a decrease in HDL cholesterol levels when challenged with a high fat diet, suggesting that the HDL levels are influenced by C7AH activity (39,40). Second, the selectively bred RICO rat showed spontaneous hypercholesterolemia that was partially attributed to a reduced activity of C7AH (41).…”

Section: Discussionmentioning

confidence: 99%

Complex genetic control of HDL levels in mice in response to an atherogenic diet. Coordinate regulation of HDL levels and bile acid metabolism.

Machleder¹,

Ivandic²,

Welch³

et al. 1997

J. Clin. Invest.

126

108

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Inbred strains of mice differ in susceptibility to atherogenesis when challenged with a high fat, high cholesterol diet containing 0.5% cholic acid. Studies of recombinant inbred (RI) strains derived from the susceptible strain C57BL/6J (B6) and the resistant strains C3H/HeJ (C3H) and BALB/cJ have revealed an association between fatty streak lesion size and a decrease in high density lipoprotein (HDL) levels on the diet. To better understand the genetic factors contributing to HDL metabolism and atherogenesis in response to the diet, we studied mice derived from an intercross between B6 and C3H using a complete linkage map approach. A total of 185 female progeny were typed for 134 genetic markers spanning the mouse genome, resulting in an average interval of about 10 cM between markers. A locus on distal chromosome 1 containing the apolipoprotein AII gene was linked to HDL-cholesterol levels on both the chow and the atherogenic diets, but this locus did not contribute to the decrease in HDL-cholesterol in response to the diet. At least three distinct genetic loci, on chromosomes 3, 5, and 11, exhibited evidence of linkage to a decrease in HDL-cholesterol after a dietary challenge. Since a bile acid (cholic acid) is required for the diet induced changes in HDL levels and for atherogenesis in these strains, we examined cholesterol-7-alpha hydroxylase (C7AH) expression. Whereas B6 mice exhibited a large decrease in C7AH mRNA levels in response to the diet, C3H showed an increase. Among the intercross mice, multiple loci contributed to the regulation of C7AH mRNA levels in response to the diet, the most notable of which coincided with the loci on chromosomes 3, 5, and 11 controlling HDL levels in response to the diet. None of these loci were linked to the C7AH structural gene which we mapped to proximal chromosome 4. These studies reveal coordinate regulation of C7AH expression and HDL levels, and they indicate that the genetic factors controlling HDL levels are more complex than previously suggested by studies of RI strains. Furthermore, we observed that two of the loci for C7AH expression contributed to differences in gall-

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Cholesterol metabolism in hypercholesterolemia-resistant rabbits

Cited by 12 publications

References 31 publications

Effect of a cholesterol-rich diet on the metabolism of the free and esterified cholesterol components of a nanoemulsion that resembles LDL in rabbits

Effect of a cholesterol-rich diet on the metabolism of the free and esterified cholesterol components of a nanoemulsion that resembles LDL in rabbits

Effect of an indigenous herbal compound preparation ‘Trikatu’ on the lipid profiles of atherogenic diet and standard diet fed Rattus norvegicus

Complex genetic control of HDL levels in mice in response to an atherogenic diet. Coordinate regulation of HDL levels and bile acid metabolism.

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