Effect of saturated and unsaturated fats on hepatic synthesis and biliary excretion of cholesterol by the rat

1959 ◽  
Vol 196 (3) ◽  
pp. 599-602 ◽  
Author(s):  
Jean D. Wilson ◽  
Marvin D. Siperstein
Keyword(s):  
Total Cholesterol ◽  
Rat Liver ◽  
Dietary Fat ◽  
Biliary Excretion ◽  
Cholesterol Synthesis ◽  
Corn Oil ◽  
Cholesterol Metabolism ◽  
Cholesterol Levels ◽  
End Products ◽  
Hepatic Synthesis

In an attempt to elucidate the mechanisms by which saturated and unsaturated fats influence cholesterol metabolism, cholesterol synthesis in rat liver slices and the excretion of cholesterol end products into the bile of rats was studied during variations in the type and quantity of dietary fat. Neither 30% lard nor 30% corn oil diets had any effect on either the excretion of total cholesterol-C14 end products or of cholesterol itself into bile. Furthermore, the feeding of lard or corn oil, at either the 10% or 30% level, had no effect on the rate of conversion of acetate or mevalonate to cholesterol. These studies are interpreted as suggesting that the effects of saturated and unsaturated fats on cholesterol levels in rats are mediated at some phase of cholesterol metabolism other than the hepatic synthesis or hepatic degradation and excretion of this sterol.

Glycerol as an inhibitor of cholesterol synthesis

1968 ◽  
Vol 46 (8) ◽  
pp. 859-863 ◽  
Author(s):  
B. B. Migicovsky
Keyword(s):  
Total Cholesterol ◽  
Rat Liver ◽  
Serum Cholesterol ◽  
Cholesterol Synthesis ◽  
Specific Radioactivity ◽  
Cholesterol Concentration ◽  
Liver Cholesterol ◽  
Water Control ◽  
Glycerol Water ◽  
Serum Cholesterol Concentration

The supernatant from a homogenate of rat liver was incubated in a system containing 14C-acetate. The mixture was then saponified, the cholesterol isolated as the digitonide, and its radioactivity determined. When glycerol (water control) was a constituent of the incubation mixture, less radioactivity appeared in the digitonide. Under the same conditions, glycerol did not apparently inhibit the incorporation of 14C-mevalonate into liver cholesterol. When rats were given glycerol or glucose by mouth then 14C-acetate intraperitoneally, the total cholesterol radioactivity, specific radioactivity, and in most cases the serum cholesterol concentration, were all lower in those rats that had been given the glycerol.

scholarly journals Two Weeks Of Western Diet Disrupts Liver Molecular Markers Of Cholesterol Metabolism In Rat

2020 ◽  
Author(s):  
Roxane St-Amand ◽  
Emilienne T. Ngo Sock ◽  
Samantha Quinn ◽  
Jean-Marc Lavoie ◽  
David H. St-Pierre
Keyword(s):  
Total Cholesterol ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Plasma Total Cholesterol ◽  
Cholesterol Levels ◽  
Density Lipoprotein Receptor ◽  
Element Binding Protein

Abstract Background: The present study was designed to test the hypothesis that in the liver, excessive fat accumulation impairs cholesterol metabolism mainly by altering the low-density lipoprotein-receptor (LDL-R) pathway. Method: Young male Wistar rats were fed standard (SD), high fat (HFD; 60% kcal) or Western (WD; 40% fat + 35% sucrose (17.5% fructose)) diets for 2 or 6 weeks. Results: Weight gain (~ 40g) was observed only following 6 weeks of the obesogenic diets (P < 0.01). Compared to the 2-week treatment, obesogenic diets tripled fat pad weight (~ 20 vs 7 g) after 6 weeks. Hepatic triglyceride (TG) levels were greater in response to both the WD and HFD compared to the SD (P < 0.01) at 2 and 6 weeks and their concentrations were greater (P < 0.05) in WD than HFD at 2 weeks. Plasma total cholesterol levels were higher (P < 0.05) in animals submitted to WD. After 2 and 6 weeks, liver expression of LDL-R, proprotein convertase subtilisin/kexin 9 (PCSKk9) and sterol regulatory element binding protein 2 (SREBP2), involved in LDL-cholesterol uptake, was lower in animals submitted to WD than in others treated with HFD or SD (P < 0.01). Similarly, low-density lipoprotein-receptor-related protein 1 (LRP1) and acyl-CoA cholesterol acyltransferase-2 (ACAT-2) mRNA levels were lower (P < 0.01) among WD compared to SD-fed rats. Expression of the gene coding the main regulator of endogenous cholesterol synthesis, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCoAR) was reduced in response to WD compared to SD and HFD at 2 (P < 0.001) and 6 (P < 0.05) weeks. Being enriched in fructose, the WD strongly promoted the expression of carbohydrate-response element binding protein (ChREBP) and acetyl-CoA carboxylase (ACC), two key regulators of de novo lipogenesis. Conclusion: These results show that the WD promptly increased TG levels in the liver by potentiating fat storage. This impaired the pathway of hepatic cholesterol uptake via the LDL-R axis, promoting a rapid increase in plasma total cholesterol levels. These results indicate that liver fat content is a factor involved in the regulation of plasma cholesterol.

Cholesterol metabolism in regenerating liver of the rat

1985 ◽  
Vol 249 (6) ◽  
pp. G679-G684 ◽  
Author(s):  
F. J. Field ◽  
S. N. Mathur ◽  
D. R. LaBrecque
Keyword(s):  
Dna Synthesis ◽  
Partial Hepatectomy ◽  
Rat Liver ◽  
Cholesterol Synthesis ◽  
Cholesterol Metabolism ◽  
Reductase Activity ◽  
Plasma Cholesterol ◽  
Regenerating Liver ◽  
Acyltransferase Activity ◽  
Regenerating Rat Liver

The regenerating rat liver was used as a model to investigate the necessity for new cholesterol synthesis prior to the onset of cell division. Plasma cholesterol levels in partially hepatectomized rats were significantly decreased 24 and 48 h after surgery compared with levels in sham-operated animals. Hepatic cholesteryl ester content was also significantly increased in livers from partially hepatectomized animals, but the hepatic content of unesterified cholesterol was not affected. Hepatic triglyceride content was significantly increased within 6 h after surgery in the regenerating liver. The triglyceride levels reached a peak at 24 h, and by 72 h they had decreased back to levels that were no different from control. In the regenerating liver, microsomal 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase activity was increased 12 h after surgery. The activity of this enzyme remained significantly elevated throughout the 72-h period after surgery. In contrast, 12 h after partial hepatectomy the rate of hepatic cholesterol synthesis was significantly lower than that observed in livers from sham-operated rats. An increase in the rate of cholesterol synthesis was not observed until 48 h after partial hepatectomy, some 32 h after the start of DNA synthesis. Microsomal acyl-CoA:cholesterol acyltransferase activity was unchanged except for a 28% decrease at 72 h after partial hepatectomy. The data suggest that new cholesterol synthesis is not a requirement prior to the initiation of DNA synthesis in the regenerating rat liver.(ABSTRACT TRUNCATED AT 250 WORDS)

LYMPHATIC ABSORPTION OF CHOLESTEROL IN THE DOG FOLLOWING CORN OIL AND BUTTERFAT FEEDING

1965 ◽  
Vol 43 (2) ◽  
pp. 299-311 ◽  
Author(s):  
T. C. Huang ◽  
A. Kuksis
Keyword(s):  
Thoracic Duct ◽  
Dietary Fat ◽  
Corn Oil ◽  
Lymphatic Absorption ◽  
Experimental Control ◽  
Cholesterol Levels ◽  
Glyceride Type ◽  
Lymph Lipid ◽  
Cholesterol Supplementation

Lymphatic absorption of cholesterol was determined in 11 unanaesthetized dogs with thoracic duct bypasses or fistulae, following the administration of corn oil or butterfat with and without cholesterol supplementation. Comparisons based on fixed amounts of lymph or total lymph lipid, as well as the estimated overall sterol recoveries, showed that the conclusions can vary depending on how the calculations are done. On the basis of data collected in the same animal, it was concluded that the glyceride type of dietary fat had no significant effect on lymphatic absorption of cholesterol in the dog. The feeding of butterfat, corn and coconut oils, or simple triglycerides to different animals resulted in widely varying lymph cholesterol levels, which could not be correlated with any of the variables under direct experimental control.

scholarly journals MYC Enhances Cholesterol Biosynthesis and Supports Cell Proliferation Through SQLE

2021 ◽  
Vol 9 ◽  
Author(s):  
Fan Yang ◽  
Junjie Kou ◽  
Zizhao Liu ◽  
Wei Li ◽  
Wenjing Du
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Cholesterol Synthesis ◽  
Cholesterol Metabolism ◽  
Cell Metabolism ◽  
Cholesterol Biosynthesis ◽  
Potential Therapeutic Target ◽  
Cholesterol Levels ◽  
Membrane Components ◽  
Rate Limiting

Oncogene c-Myc (referred in this report as MYC) promotes tumorigenesis in multiple human cancers. MYC regulates numerous cellular programs involved in cell growth and cell metabolism. Tumor cells exhibit obligatory dependence on cholesterol metabolism, which provides essential membrane components and metabolites to support cell growth. To date, how cholesterol biosynthesis is delicately regulated to promote tumorigenesis remains unclear. Here, we show that MYC enhances cholesterol biosynthesis and promotes cell proliferation. Through transcriptional upregulation of SQLE, a rate-limiting enzyme in cholesterol synthesis pathway, MYC increases cholesterol production and promotes tumor cell growth. SQLE overexpression restores the cellular cholesterol levels in MYC-knockdown cells. More importantly, in SQLE-depleted cells, enforced expression of MYC has no effect on cholesterol levels. Therefore, our findings reveal that SQLE is critical for MYC-mediated cholesterol synthesis, and further demonstrate that SQLE may be a potential therapeutic target in MYC-amplified cancers.

scholarly journals Two Weeks Of Western Diet Disrupts Liver Molecular Markers Of Cholesterol Metabolism In Rat

2020 ◽  
Author(s):  
Roxane St-Amand ◽  
Emilienne T. Ngo Sock ◽  
Samantha Quinn ◽  
Jean-Marc Lavoie ◽  
David H. St-Pierre
Keyword(s):  
Total Cholesterol ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Plasma Total Cholesterol ◽  
Cholesterol Levels ◽  
Density Lipoprotein Receptor ◽  
Element Binding Protein

Abstract Background: The present study was designed to test the hypothesis that in the liver, excessive fat accumulation impairs cholesterol metabolism mainly by altering the low-density lipoprotein-receptor (LDL-R) pathway. Method: Young male Wistar rats were fed standard (SD), high fat (HFD; 60% kcal) or Western (WD; 40% fat + 35% sucrose (17.5% fructose)) diets for 2 or 6 weeks. Results: Weight gain (~ 40g) was observed only following 6 weeks of the obesogenic diets (P < 0.01). Compared to the 2-week treatment, obesogenic diets tripled fat pad weight (~ 20 vs 7 g) after 6 weeks. Hepatic triglyceride (TG) levels were greater in response to both the WD and HFD compared to the SD (P < 0.01) at 2 and 6 weeks and their concentrations were greater (P < 0.05) in WD than HFD at 2 weeks. Plasma total cholesterol levels were higher (P < 0.05) in animals submitted to WD. After 2 and 6 weeks, liver expression of LDL-R, proprotein convertase subtilisin/kexin 9 (PCSKk9) and sterol regulatory element binding protein protein 2 (SREBP2), involved in LDL-cholesterol uptake, was lower in animals submitted to WD than in others treated with HFD or SD (P < 0.01). Similarly, low-density lipoprotein-receptor-related protein 1 (LRP1) and acyl-CoA cholesterol acyltransferase-2 (ACAT-2) mRNA levels were lower (P < 0.01) among WD compared to SD-fed rats. Expression of the gene coding the main regulator of endogenous cholesterol synthesis, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCoAR) was reduced in response to WD compared to SD and HFD at 2 (P < 0.001) and 6 (P < 0.05) weeks. Being enriched in fructose, the WD strongly promoted the expression of carbohydrate-response element binding protein (ChREBP) and acetyl-CoA carboxylase (ACC), two key regulators of de novo lipogenesis. Conclusion: These results show that the WD promptly increased TG levels in the liver by potentiating fat storage. This impaired the pathway of hepatic cholesterol uptake via the LDL-R axis, promoting a rapid increase in plasma total cholesterol levels. These results indicate that liver fat content is a factor involved in the regulation of plasma cholesterol.

Total Cholesterol and APOE-Related Risk for Alzheimer’s Disease in the Alzheimer’s Disease Neuroimaging Initiative

2021 ◽  
pp. 1-10
Author(s):  
Michelle M. Dunk ◽  
Ira Driscoll ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Total Cholesterol ◽  
Cholesterol Metabolism ◽  
Apoe Genotype ◽  
Control Group ◽  
Cholesterol Levels ◽  
Related Risk ◽  
E4 Allele

Background: APOE ɛ4 allele confers greatest genetic risk for Alzheimer’s disease (AD), yet mechanisms underlying this risk remain elusive. APOE is involved in lipid metabolism, and literature suggest relationships between high total cholesterol, APOE, and AD. Further investigation is needed to elucidate the potential role of total cholesterol in AD risk. Objective: To investigate the relationship between total cholesterol and APOE-related AD risk in the Alzheimer’s Disease Neuroimaging Initiative. Methods: Participants (N = 1,534) were classified as controls (cognitively normal; N = 404), early mild cognitive impairment (MCI; N = 294), late MCI (N = 539), or AD (N = 297). Total cholesterol levels were compared across APOE genotype and diagnosis. Mendelian randomization was performed to examine causality between total cholesterol and AD risk using APOE as a genetic instrument. Results: Total cholesterol was higher in APOE4+ compared to APOE3 and APOE2+ (ps < 0.04) carriers. Those with AD and late MCI (ps < 0.001) had higher total cholesterol than the control group. Comparing APOE4+ to APOE3 carriers, the predicted odds ratios per mg/dL greater total cholesterol were 1.11 for MCI (95% confidence interval, 1.04–7.32), 1.05 for early MCI (1.01–3.22), 1.13 for late MCI (1.05–11.70), 1.21 for AD (1.09–54.05), and 1.13 for composite dementia (MCI or AD; 1.06–11.59) (ps < 0.05, F-statistics>10). Conclusion: Higher total cholesterol may be a significant contributor to AD risk, particularly in APOE4 carriers who, based on existing literature, tend to have impaired cholesterol metabolism. Our findings highlight a possible mechanism by which APOE confers AD risk and indicate potential for AD risk modification through maintenance of healthy total cholesterol levels.

scholarly journals Olive oil and rapeseed oil differ in their effect on plasma low-density lipoprotein metabolism in the guinea-pig

1996 ◽  
Vol 76 (6) ◽  
pp. 869-880 ◽  
Author(s):  
Maria Luz Fernandez ◽  
Anthony E. Soscia ◽  
Gwo-Shing Sun ◽  
Mark Tosca ◽  
Donald J. McNamara ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Guinea Pig ◽  
Olive Oil ◽  
Dietary Fat ◽  
Rapeseed Oil ◽  
Ldl Cholesterol ◽  
Cholesterol Metabolism ◽  
Hepatic Cholesterol ◽  
Apo B ◽  
Cholesterol Levels

The effects of olive oil and rapeseed oil, two different high-o1eic-acid oils, on plasma LDL and hepatic cholesterol metabolism were compared in guinea-pigs. Animals were fed on semipurified diet containing 150 g fat/kg as either olive oil (OL), rapeseed oil plus 100 g palm oil/kg (C-P) or olive oil plus 350 g safflowerseed oil/kg (OL-S). Olive oil was enriched with safllowerseed oil (OL-S diet) to increase linoleic acid and to decrease palmitic acid concentrations, in order to evaluate whether differences in plasma LDL concentrations were due to intrinsic effects of the specific oil (rapeseed or olive oil) or to differences in the content of specific fatty acids. No differences due to dietary fat source were found in plasma total and HDL-cholesterol levels or in LDL composition. Plasma LDL-cholesterol levels were lower on the C-P diet than the OL diet (P< 0·05) while plasma LDL-cholesterol levels in animals fed on the OL-S diet were not significantly different from either dietary group (P> 0·05). The number of hepatic apo B/E (LDL) receptors was on average 25% higher in animals fed on the C-P diet compared with those fed on diets containing olive oil. Likewise, cardiac muscle lipoprotein lipase (EC3.1.1.34) activity was significantly higher in the C-P group than in the OL and OL-S dietary groups. Dietary fat source had no effect on hepatic cholesterol levels or 3-hydroxy-3-methylglutaryl (HMG) CoA reductase (EC1.1.1.34) activity. The results indicate that olive oil and rapeseed oil, both rich sources of monoumaturated fatty acids, differ in their effect on LDL metabolism in the guinea-pig.

Tamoxifen and toremifene lower serum cholesterol by inhibition of delta 8-cholesterol conversion to lathosterol in women with breast cancer.

1995 ◽  
Vol 13 (12) ◽  
pp. 2900-2905 ◽  
Author(s):  
H Gylling ◽  
S Pyrhönen ◽  
E Mäntylä ◽  
H Mäenpää ◽  
L Kangas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cholesterol Synthesis ◽  
Ldl Cholesterol ◽  
Cholesterol Metabolism ◽  
Density Lipoprotein ◽  
Tamoxifen Treatment ◽  
Gas Liquid Chromatography ◽  
Hypolipidemic Effect ◽  
Cholesterol Levels

PURPOSE Long-term effects of tamoxifen and toremifene, a new antiestrogen that closely resembles tamoxifen, were investigated on serum lipids and cholesterol metabolism. PATIENTS AND METHODS The study group consisted of 24 postmenopausal Finnish women with advanced breast cancer from an international multicenter study of 415 patients. Cholesterol metabolism was evaluated by measuring the cholesterol precursor (delta 8-cholestenol, desmosterol, and lathosterol, reflecting cholesterol synthesis) and plant sterol (markers of cholesterol absorption) and cholestanol levels by gas-liquid chromatography. RESULTS Tamoxifen and toremifene lowered significantly serum low-density lipoprotein (LDL) cholesterol levels after 12 months of treatment by 16% and 15%, with no change in high-density lipoprotein (HDL) cholesterol or serum triglyceride levels. Serum delta 8-cholestenol was increased 40- and 55-fold during toremifene and tamoxifen treatment, respectively, while the increase of desmosterol less than doubled and was lacking for lathosterol by toremifene. Plant sterols and cholestanol were only inconsistently increased in serum. CONCLUSION Tamoxifen and toremifene inhibit the conversion of delta 8-cholestenol to lathosterol so that serum total and LDL cholesterol levels are lowered by downregulation of cholesterol synthesis. Thus, inhibition of the delta 8-isomerase may be the major hypolipidemic effect of these agents. Reduced risk of coronary artery disease will probably occur also during long-term toremifene treatment, because the drug reduces cholesterol and its synthesis, similarly to tamoxifen.

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