scholarly journals Prague hereditary hypercholesterolemic (PHHC) rat – a model of polygenic hypercholesterolemia

2009 ◽  
pp. S95-S100
Author(s):  
J Kovář ◽  
Z Tonar ◽  
M Heczková ◽  
R Poledne
Keyword(s):  
Bile Salts ◽  
Wistar Rats ◽  
Turnover Rate ◽  
Cholesterol Synthesis ◽  
Dietary Cholesterol ◽  
Antithyroid Drugs ◽  
Cholesterol Diet ◽  
Microarray Gene Expression ◽  
Ldl Catabolism ◽  
Rat Strain

Prague hereditary hypercholesterolemic (PHHC) rat – rat strain crossbred from Wistar rats – is a model of hypercholesterolemia induced by dietary cholesterol. Importantly, no bile salts and/or antithyroid drugs need to be added to the diet together with cholesterol to induce hypercholesterolemia. PHHC rats have only modestly increased cholesterolemia when fed a standard chow and develop hypercholesterolemia exceeding 5 mmol/l on 2 % cholesterol diet. Most of the cholesterol in hypercholesterolemic PHHC rats is found in VLDL that become enriched with cholesterol (VLDL-C/VLDL-TG ratio > 1.0). Concurrently, both IDL and LDL concentrations rise without any increase in HDL. PHHC rats do not markedly differ from Wistar rats in the activities of enzymes involved in intravascular remodelation of lipoproteins (lipoprotein and hepatic lipases and lecithin:cholesterol acyltransferase), LDL catabolism, cholesterol turnover rate and absorption of dietary cholesterol. The feeding rats with cholesterol diet results in development of fatty liver in spite of suppression of cholesterol synthesis. However, even though cholesterolemia in PHHC rats is comparable to human hypercholesterolemia, the PHHC rats do not develop atherosclerosis even after 6 months on 2 % cholesterol diet. Importantly, the crossbreeding experiments documented that hypercholesterolemia of PHHC rats is polygenic. To identify the genes that may be involved in pathogenesis of hypercholesterolemia in this strain, the studies of microarray gene expression in the liver of PHHC rats are currently in progress.

scholarly journals Increased circulating LDL cholesterol increases myeloma tumour burden in vivo

2021 ◽  
Vol 2 (4) ◽  
Author(s):  
Beatriz Gamez
Keyword(s):  
Bone Disease ◽  
Dietary Intervention ◽  
Dietary Cholesterol ◽  
Cholesterol Diet ◽  
Tumour Burden ◽  
Benign Condition ◽  
Myeloma Cells ◽  
Osteolytic Bone Disease

Gámez B., Morris EV., Olechnowicz S., Sowman, A., Turner, C. and Edwards CM.   Multiple myeloma (MM) is a fatal malignancy characterized by an expansion of malignant plasma cells in the bone marrow (BM) and associated with osteolytic bone disease. MM is preceded by the benign condition, monoclonal gammopathy of undetermined significance (MGUS). Understanding MGUS progression and development of MM bone disease is key for patient management. We and others have previously demonstrated that diet-induced obesity promotes myeloma progression, but the mechanisms underlying this remain unknown. The aim of the current study was to determine the effect of dietary cholesterol on MM development. A 2% cholesterol diet was used to increase circulating LDL in mice. Mice were randomly distributed to either a) cholesterol diet 4 weeks prior to 5TGM1 MM inoculation (pretreatment) or b) cholesterol diet 4 weeks prior to MM inoculation and continued for the entire experiment (continuous). Mice on the continuous cholesterol diet had increased tumour burden, associated with an increase in lipid droplet content of MM cells. No differences in tumour burden were seen in those mice where cholesterol diet was halted at time of MM inoculation. In vitro, myeloma cells cultured with delipidated FBS had a 50% reduction in viability after 72 hours. Rich cholesterol content lipoproteins (LDL) but not VLDL could restore MM cell viability, suggesting that cholesterol is responsible for this lipid-depletion effect. Taken together, our results show that high cholesterol promotes myeloma and results in a higher lipid content in myeloma cells, ultimately increasing BM tumour burden. Pretreatment with a cholesterol diet did not alter disease progression suggesting a direct pro-tumourigenic effect of cholesterol. These results demonstrate both the detrimental effect of cholesterol on myeloma progression and the potential for dietary intervention approaches.

scholarly journals Effects of dietary cholesterol and fat on serum non-cholesterol sterols according to different apolipoprotein E subgroups among healthy men

2008 ◽  
Vol 100 (2) ◽  
pp. 373-379 ◽  
Author(s):  
Markku J. Nissinen ◽  
Helena Gylling ◽  
Tatu A. Miettinen
Keyword(s):  
Cholesterol Synthesis ◽  
Cholesterol Metabolism ◽  
Dietary Cholesterol ◽  
Serum Levels ◽  
High Cholesterol ◽  
High Fat ◽  
Low Fat ◽  
Apo E ◽  
The Impact ◽  
Low Cholesterol

The impact of apo E phenotypes on applicability of relative cholesterol synthesis (lathosterol:cholesterol) and absorption (ratios of cholestanol, campesterol and sitosterol to cholesterol) during diets of various cholesterol and fat content is unclear. We examined and compared with each other both relative and absolute synthesis and absorption among twenty-nine men, of whom eight, nine and twelve had apo E phenotypes 2 (2/2, 2/3, 2/4), 3 (3/3) and 4 (3/4, 4/4), respectively. Serum lipids, lipoproteins, sterols and cholesterol metabolism were examined on four subsequent diets: high-cholesterol high-fat (home diet; HD), low-cholesterol low-fat (LCLF), high-cholesterol low-fat (HCLF) and low-cholesterol high-fat (LCHF). LDL-cholesterol (LDL-C) level was about 40 % lower (P < 0·05) in apo E2 than apo E3 and E4 groups irrespective of dietary fat and cholesterol. Serum proportions of phytosterols were determined apo E-dependently on LCLF and HCLF, and those of lathosterol, cholestanol and campesterol were increased in apo E2 and E3 groups (P < 0·05 for each v. HD). Serum proportion of sitosterol reflected almost consistently apo E phenotype (r range+0·308 to+0·383; P range 0·214–0·011). Relative cholesterol synthesis and absorption reflected respective absolute values during each diet in the apo E4 group (r range+0·713 to+0·893; P < 0·05 for each), but only during HD (r+0·594; P = 0·015) in the apo E2+E3 group. The consumption of a high amount of fat did not interfere with cholesterol metabolism or serum levels of LDL-C differently in apo E phenotypes. Surrogate sterol markers of cholesterol metabolism reflected absolute ones (especially in the apo E4 group) and apo E phenotypes despite variable amounts of dietary cholesterol and fat.

scholarly journals Dietary Cholesterol Concentration and Duration Degrade Long-Term Memory of Classical Conditioning of the Rabbit’s Nictitating Membrane Response

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Bernard G. Schreurs ◽  
Desheng Wang ◽  
Carrie A. Smith-Bell ◽  
Lauren B. Burhans ◽  
Roger Bell ◽  
...  
Keyword(s):  
Dietary Cholesterol ◽  
Trace Conditioning ◽  
Cholesterol Concentration ◽  
Long Term Memory ◽  
Cholesterol Diet ◽  
Nictitating Membrane ◽  
Term Memory ◽  
Cholesterol Levels ◽  
Nictitating Membrane Response

A rabbit model of Alzheimer’s disease based on feeding a cholesterol diet for eight weeks shows sixteen hallmarks of the disease, including learning and memory changes. Although we have shown 2% cholesterol and copper in water can retard learning, other studies show feeding dietary cholesterol before learning can improve acquisition whereas feeding cholesterol after learning can degrade long-term memory. We explored this issue by manipulating cholesterol concentration and duration following classical trace conditioning of the rabbit’s nictitating membrane response and assessed conditioned responding after eight weeks on cholesterol. First, rabbits given trace classical conditioning followed by 0.5%, 1%, or 2% cholesterol for eight weeks showed body weight and serum cholesterol levels that were a function of dietary cholesterol. Although all concentrations of cholesterol showed some sign of retarding long-term memory, the level of memory retardation was correlated with serum cholesterol levels. Second, rabbits given trace conditioning followed by different durations of a 2% cholesterol diet combined with different durations of a 0% control diet for 8 weeks showed duration and timing of a 2% cholesterol diet were important in affecting recall. The data support the idea that dietary cholesterol may retard long-term memory.

scholarly journals Effects of Nori- and Wakame-enriched meats with or without supplementary cholesterol on arylesterase activity, lipaemia and lipoproteinaemia in growing Wistar rats

2011 ◽  
Vol 106 (10) ◽  
pp. 1476-1486 ◽  
Author(s):  
Raúl Olivero-David ◽  
Adriana Schultz-Moreira ◽  
Miguel Vázquez-Velasco ◽  
Laura González-Torres ◽  
Sara Bastida ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Plasma Cholesterol ◽  
Dietary Cholesterol ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Control Group ◽  
Vldl Cholesterol ◽  
Freeze Dried ◽  
Cholesterol Supplementation ◽  
Two Parameters

Some seaweeds exert antioxidant and hypocholesterolaemic properties. The effects of diets including restructured meats (RM) containing Wakame (W) or Nori (N) algae on arylesterase (AE) activity and lipoprotein concentration and composition were tested. In the present study, six groups of ten male growing Wistar rats each were fed a mix of 85 % AIN-93M diet and 15 % freeze-dried RM for 35 d. The control group (C) consumed control RM, the W and N groups consumed RM with 5 % W and 5 % N, respectively. The cholesterol-enriched C (CC), W (CW) and N (CN) groups consumed their corresponding basal diets with supplementary cholesterol (2·43 %) and cholic acid (0·49 %). Cholesterol in the diet induced lower (P < 0·001) growth ratios. Both W and N diets significantly increased AE activity. VLDL-cholesterol values were lower in N rats than in W rats. AE activity increased (P < 0·001) in CC and CW rats but not in CN rats compared with their corresponding counterparts. AE was lower (P < 0·05) in the CN group than in the CC and CW groups. The CN diet partially blocked (P < 0·001) the hypercholesterolaemic induction observed in CC and CW diets and reduced TAG levels (at least P < 0·05) with respect to those of CC rats. Although dietary cholesterol supplementation increased total cholesterol, VLDL-cholesterol and (intermediate-density lipoprotein+LDL)-cholesterol (all P < 0·001) in all rats, the CN diet moderately improved the lipoprotein profile of hypercholesterolaemic rats. Changes in AE activity and plasma cholesterol in CN rats but not in CW rats suggest a possible relationship between the two parameters. It is concluded that inclusion of RM enriched with N may be used in hypercholesterolaemic diets to improve lipoprotein metabolism.

Effects of dietary flaxseed on vascular contractile function and atherosclerosis during prolonged hypercholesterolemia in rabbits

2006 ◽  
Vol 291 (6) ◽  
pp. H2987-H2996 ◽  
Author(s):  
C. M. C. Dupasquier ◽  
A.-M. Weber ◽  
B. P. Ander ◽  
P. P. Rampersad ◽  
S. Steigerwald ◽  
...  
Keyword(s):  
Vascular Function ◽  
Contractile Function ◽  
Plasma Cholesterol ◽  
Dietary Cholesterol ◽  
Relaxation Response ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Beneficial Effects ◽  
Atherosclerotic Lesions

Dietary flaxseed has significant anti-atherogenic effects. However, the limits of this action and its effects on vascular contractile function are not known. We evaluated the effects of flaxseed supplementation on atherosclerosis and vascular function under prolonged hypercholesterolemic conditions in New Zealand White rabbits assigned to one of four groups for 6, 8, or 16 wk of feeding: regular diet (RG), 10% flaxseed-supplemented diet (FX), 0.5% cholesterol-supplemented diet (CH), and 0.5% cholesterol- and 10% flaxseed-supplemented diet (CF). Cholesterol feeding resulted in elevated plasma cholesterol levels and the development of atherosclerosis. The CF group had significantly less atherosclerotic lesions in the aorta and carotid arteries after 6 and 8 wk than the CH animals. However, the anti-atherogenic effect of flaxseed supplementation was completely attenuated by 16 wk. Maximal tension induced in aortic rings either by KCl or norepinephrine was not impaired by dietary cholesterol until 16 wk. This functional impairment was not prevented by including flaxseed in the high-cholesterol diet. Aortic rings from the cholesterol-fed rabbits exhibited an impaired relaxation response to acetylcholine at all time points examined. Including flaxseed in the high-cholesterol diet completely normalized the relaxation response at 6 and 8 wk and partially restored it at 16 wk. No significant changes in the relaxation response induced by sodium nitroprusside were observed in any of the groups. In summary, dietary flaxseed is a valuable strategy to limit cholesterol-induced atherogenesis as well as abnormalities in endothelial-dependent vasorelaxation. However, these beneficial effects were attenuated during prolonged hypercholesterolemic conditions.

scholarly journals Improvement on high-cholesterol diet induced atherosclerosis, lipid profile, oxidative stress and genotoxicity in the liver of mice by Echinops spinosissimus Turra subsp. spinosus

2020 ◽  
Author(s):  
Donyez Frikha Dammak ◽  
Hajer Ben Saad ◽  
Emna Bouattour ◽  
Ons Boudawara ◽  
Raoudha Mezghani Jarraya
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activities ◽  
Dietary Cholesterol ◽  
Atherogenic Index ◽  
High Cholesterol Diet ◽  
Antioxidant Compounds ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Oxidative Stress Biomarkers

Abstract Background Hypercholesterolemia is a major risk factor for the development of atherosclerosis and endothelial dysfunction. Methods The present study investigates the possible mechanism of Echinops spinosissimus Turra subsp. spinosus ( E. s. spinosus ) flower on the high cholesterol diet. Results Our in vitro results demonstrated the richness of E.s. spinosus flower in antioxidant compounds, and its antioxidant activities. The co-administration of E.s. spinosus (100 or 200 mg/kg/day) with high-fat diet attenuated hepatotoxicity as monitored by the improvement of oxidative stress biomarkers and plasma lipid and liver parameters, when compared to the hypercholesterolemic mice. Atherogenic index and body weight were also reduced markedly, compared to control mice. These results were confirmed by the improvement of histological changes and DNA damage. Conclusion These data indicate that E.s. spinosus flower reduces the hypercholesterolemia risk and atherogenic properties of dietary cholesterol. Its hypocholesterolemic effect may be due to its antioxidant activities and its richness in bioactive molecule.

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