scholarly journals Chronic Oral Administration of Mineral Oil Compared With Corn Oil: Effects on Gut Permeability and Plasma Inflammatory and Lipid Biomarkers

2021 ◽  
Vol 12 ◽  
Author(s):  
Elsbet J. Pieterman ◽  
Hans M. G. Princen ◽  
Annica Jarke ◽  
Ralf Nilsson ◽  
Anders Cavallin ◽  
...  
Keyword(s):  
Oral Administration ◽  
Intestinal Permeability ◽  
Plasma Lipids ◽  
Corn Oil ◽  
Plasma Cholesterol ◽  
Mineral Oil ◽  
Lipopolysaccharide Binding Protein ◽  
Protein Levels ◽  
Cholesterol Excretion ◽  
Fecal Cholesterol

We investigated the effects of chronic oral administration of mineral oil, versus corn oil as control, on intestinal permeability, inflammatory markers, and plasma lipids in APOE*3-Leiden.CETP mice. Mice received mineral oil or corn oil 15 or 30 μL/mouse/day for 16 weeks (15 mice/group). Intestinal permeability was increased with mineral versus corn oil 30 µL/day, shown by increased mean plasma FITC-dextran concentrations 2 h post-administration (11 weeks: 1.5 versus 1.1 μg/ml, p = 0.02; 15 weeks: 1.7 versus 1.3 μg/ml, p = 0.08). Mean plasma lipopolysaccharide-binding protein levels were raised with mineral versus corn oil 30 µL/day (12 weeks: 5.8 versus 4.4 μg/ml, p = 0.03; 16 weeks: 5.8 versus 4.5 μg/ml, p = 0.09), indicating increased intestinal bacterial endotoxin absorption and potential pro-inflammatory effects. Plasma cholesterol and triglyceride concentrations were decreased with mineral oil, without affecting liver lipids among treated groups. Fecal neutral sterol measurements indicated increased fecal cholesterol excretion with mineral oil 30 µL/day (+16%; p = 0.04). Chronic oral administration of mineral oil in APOE*3-Leiden.CETP mice increased intestinal permeability, with potential pro-inflammatory effects, and decreased plasma cholesterol and triglyceride levels. Our findings may raise concerns about the use of mineral oil as a placebo in clinical studies.

Abstract 424: Transintestinal Cholesterol Excretion Can Drive Massive Cholesterol Elimination in Mice

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Jan F De Boer ◽  
Marleen Schonewille ◽  
Marije Boesjes ◽  
Henk Wolters ◽  
Vincent W Bloks ◽  
...  
Keyword(s):  
Plasma Cholesterol ◽  
Decisive Role ◽  
Cholesterol Absorption ◽  
The Body ◽  
Farnesoid X Receptor ◽  
Intestinal Lumen ◽  
Knock Out ◽  
Cholesterol Levels ◽  
Cholesterol Excretion ◽  
Fecal Cholesterol

High plasma cholesterol levels increase the risk of cardiovascular disease (CVD). Transintestinal Cholesterol Excretion (TICE) is a recently emerged pathway of cholesterol removal and has the potential to lower plasma cholesterol levels and confer protection against CVD. Under control conditions, TICE accounts for about 30% of fecal cholesterol loss in mice. Using a panel of knock-out and transgenic mice as well as pharmacological manipulations we show that in mice TICE is regulated by intestinal activation of the Farnesoid X Receptor (FXR), via its target Fibroblast Growth Factor 15/19 (FGF15/19). Activation of FXR by the agonist PX20606 (PX) resulted in a >10-fold increased fecal cholesterol excretion as well as TICE and 40% reduced plasma cholesterol levels. The induction of fecal cholesterol excretion and TICE was absent in PX-treated intestine-specific FXR-null mice but was regained when those mice were co-treated with FGF19. Moreover, FGF19 treatment alone was sufficient to induce fecal cholesterol loss to a similar extend as was observed in PX-treated wild-type mice. PX treatment resulted in an increased muricholate/cholate-ratio and thereby induced a more hydrophilic bile salt pool. Not surprisingly, cholesterol absorption was reduced in PX-treated mice. However, experiments in which mice were co-treated with PX and the cholesterol absorption inhibitor ezetimibe revealed that the stimulating effect of PX on fecal neutral sterol excretion and TICE were completely independent of differences in cholesterol absorption. Of note, treatment of mice with a combination of PX and ezetimibe stimulated fecal cholesterol loss and TICE so strongly that those mice lost about 60% of their entire estimated body cholesterol content each day. The stimulation of fecal cholesterol loss and TICE by PX and PX/ezetimibe treatment was severely blunted in Abcg8-KO mice and this could not be restored by hepatic reintroduction of Abcg8, indicating a decisive role for intestinal ABCG5/G8 in PX-induced fecal cholesterol loss and TICE. Our data strongly suggest that hydrophilic bile acids stimulate ABCG5/G8 activity in the intestine, leading to an increased flux of cholesterol from the body into the intestinal lumen that is subsequently excreted with the feces.

Glycosphingolipid synthesis inhibitor AMP-DNM lowers plasma cholesterol levels by promoting fecal cholesterol excretion without inhibiting cholesterol absorption

2012 ◽  
Vol 7 (2) ◽  
pp. 241-248
Author(s):  
Carlos LJ Vrins ◽  
Florence Bietrix ◽  
Elisa Lombardo ◽  
Cindy PPA van Roomen ◽  
Roelof Ottenhoff ◽  
...  
Keyword(s):  
Plasma Cholesterol ◽  
Cholesterol Absorption ◽  
Synthesis Inhibitor ◽  
Cholesterol Levels ◽  
Cholesterol Excretion ◽  
Fecal Cholesterol

The Effect of n-3 Fatty Acids on Lipids and Haemostasis in Patients with Type lla and Type IV Hyperlipidaemia

1989 ◽  
Vol 62 (02) ◽  
pp. 797-801 ◽  
Author(s):  
E Berg Schmidt ◽  
E Ernst ◽  
K Varming ◽  
J O Pedersen ◽  
J Dyerberg
Keyword(s):  
Fatty Acids ◽  
Plasma Lipids ◽  
Plasma Cholesterol ◽  
Hdl Cholesterol ◽  
Apolipoprotein A1 ◽  
Type Iv ◽  
Before And After ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen

SummaryPlasma lipids and haemostasis were investigated in 17 patients with hyperlipidaemia before and after 6 weeks supplementation with 6 g n-3 fatty acids. Nine of the patients had type IIa and 8 had type IV hyperlipidaemia. No effect on plasma cholesterol, LDL- or HDL-cholesterol were seen, but plasma triglycerides decreased after n-3 supplementation. Apolipoprotein B increased and apolipoprotein A1 decreased after the oil supplement. The bleeding time was prolonged, but platelet aggregation was unaltered by n-3 fatty acids. Protein C activity increased in type II a and decreased in type IV after the supplement. Fibrinolysis was markedly depressed while von Willebrand factor antigen was reduced after intake of n-3 fatty acids.

Evaluation of Glucose and Lipid Lowering Activity of Arganimide A in Normal and Streptozotocin-Induced Diabetic Rats

2019 ◽  
Vol 19 (4) ◽  
pp. 503-510 ◽  
Author(s):  
Mohamed Eddouks ◽  
Farid Khallouki ◽  
Robert W. Owen ◽  
Morad Hebi ◽  
Remy Burcelin
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
Oral Administration ◽  
Lipid Profile ◽  
Plasma Cholesterol ◽  
Diabetic Rats ◽  
Lipid Lowering ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Lowering Activity

Aims: Arganimide A (4,4-dihydroxy-3,3-imino-di-benzoic acid) is a compound belonging to a family of aminophenolics found in fruit of Argania spinosa. The purpose of this study was to investigate the glucose and lipid lowering activity of Arganimide A (ARG A). Methods: The effect of a single dose and daily oral administration of Arganimide A (ARG A) on blood glucose levels and plasma lipid profile was tested in normal and streptozotocin (STZ) diabetic rats at a dose of 2 mg/kg body weight. Results: Single oral administration of ARG A reduced blood glucose levels from 26.50±0.61 mmol/L to 14.27±0.73 mmol/L (p<0.0001) six hours after administration in STZ diabetic rats. Furthermore, blood glucose levels were decreased from 5.35±0.30 mmol/L to 3.57±0.17 mmol/L (p<0.0001) and from 26.50±0.61 mmol/L to 3.67±0.29 mmol/L (p<0.0001) in normal and STZ diabetic rats, respectively, after seven days of treatment. Moreover, no significant changes in body weight in normal and STZ rats were shown. According to the lipid profile, the plasma triglycerides levels were decreased significantly in diabetic rats after seven days of ARG treatment (p<0.05). Moreover, seven days of ARG A treatment decreased significantly the plasma cholesterol concentrations (p<0.001). Conclusion: ARG A possesses glucose and lipid-lowering activity in diabetic rats and this natural compound may be beneficial in the treatment of diabetes.

Plasma Lipid-lowering and Lipogenesis-stimulating Actions of Ginseng Saponins in Tumor-bearing Rats

1983 ◽  
Vol 11 (01n04) ◽  
pp. 88-95 ◽  
Author(s):  
Masahiro Yamamoto ◽  
Akira Kumagai ◽  
Yuichi Yamamura
Keyword(s):  
Adipose Tissue ◽  
Oral Administration ◽  
Plasma Cholesterol ◽  
Lipid Fraction ◽  
Plasma Lipid ◽  
Male Rats ◽  
Lipid Lowering ◽  
Tumor Bearing ◽  
Saponin Content

Ascited hepatoma (AH41C or AH130) was transplanted to male rats Donryu, strain. Plasma cholesterol, triglyceride (TG) and non-esterified fatty acid levels were reduced with oral administration of ginseng principle fraction 3 (saponin content, ca. 1/5). Incorporation of 1-[14C]-acetate into total lipids and fatty acids in adipose tissue was increased by fraction 3 administration in both normal and tumor-bearing rats. The incorporation increased in earlier stage of tumor growth and decreased in the later one. Incorporation of 1-[14C]-acetate into total lipid, free and esterified cholesterol, TG and phospholipid in the liver was also enhanced by fraction 3 administration in both normal and tumor-bearing animals. In vitro addition of ginseng principle fraction 4 (saponin content, ca. 1/2) increased incorporation of 1-[14C]-acetate into lipid fraction is adipose tissue and liver. Incorporation of 1-[14C]-acetate into lipid fractions in ascites hepatoma cells remained unchanged with both oral administration of fraction 3 and in vitro addition of fraction 4. DNA and protein synthesis in the tumor cells was not changed with in vitro addition of fraction 4.

scholarly journals APOE4 Genotype Exerts Greater Benefit in Lowering Plasma Cholesterol and Apolipoprotein B than Wild Type (E3/E3), after Replacement of Dietary Saturated Fats with Low Glycaemic Index Carbohydrates

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1524 ◽  
Author(s):  
Bruce Griffin ◽  
Celia Walker ◽  
Susan Jebb ◽  
Carmel Moore ◽  
Gary Frost ◽  
...  
Keyword(s):  
Glucose Homeostasis ◽  
Apolipoprotein B ◽  
Dietary Intervention ◽  
Plasma Lipids ◽  
Plasma Cholesterol ◽  
Apoe Genotype ◽  
Density Lipoprotein ◽  
Glycaemic Index ◽  
Apo B ◽  
The Impact

We examined the impact of APOE genotype on plasma lipids and glucose in a secondary analysis of data from a five-arm, randomised controlled, parallel dietary intervention trial (‘RISCK’ study), to investigate the impact of replacing saturated fatty acids (SFA) with either monounsaturated fat (MUFA) or carbohydrate of high or low glycaemic index (GI) on CVD risk factors and insulin sensitivity. We tested the impact of APOE genotype (carriage of E2 and E4 alleles versus E3/E3), determined retrospectively, on plasma lipids, lipoproteins and glucose homeostasis at baseline (n = 469), and on the change in these variables after 24 weeks of dietary intervention (n = 389). At baseline, carriers of E2 (n = 70), E4 (n = 125) and E3/E3 (n = 274) expressed marked differences in total plasma cholesterol (TC, p = 0.001), low density lipoprotein cholesterol (LDL-C, p < 0.0001), apolipoprotein B (apo B, p < 0.0001) and total to high density lipoprotein cholesterol ratio (TC:HDL-C, p = 0.002), with plasma concentrations decreasing in the order E4 > E3/E3 > E2. Following intervention, there was evidence of a significant diet x genotype interaction with significantly greater decreases in TC (p = 0.02) and apo B (p = 0.006) among carriers of E4 when SFA was replaced with low GI carbohydrate on a lower fat diet (TC −0.28 mmol/L p = 0.03; apo B −0.1 g/L p = 0.02), and a relative increase in TC (in comparison to E3/E3) when SFA was replaced with MUFA and high GI carbohydrates (TC 0.3 mmol/L, p = 0.03). Among carriers of E2 (compared with E3/E3) there was an increase in triacylglycerol (TAG) when SFA was replaced with MUFA and low GI carbohydrates 0.46 mmol/L p = 0.001). There were no significant interactions between APOE genotype and diet for changes in indices of glucose homeostasis. In conclusion, variations in APOE genotype led to differential effects on the lipid response to the replacement of SFA with MUFA and low GI carbohydrates.

scholarly journals A relaxometric method for the assessment of intestinal permeability based on the oral administration of gadolinium-based MRI contrast agents

2016 ◽  
Vol 29 (4) ◽  
pp. 475-482 ◽  
Author(s):  
Eliana Gianolio ◽  
Cinzia Boffa ◽  
Valeria Orecchia ◽  
Paola Bardini ◽  
Valeria Catanzaro ◽  
...  
Keyword(s):  
Oral Administration ◽  
Contrast Agents ◽  
Intestinal Permeability ◽  
Mri Contrast Agents ◽  
Mri Contrast

scholarly journals Effect of chronic renal failure on the hepatic, intestinal, and renal expression of bile acid transporters

2014 ◽  
Vol 306 (1) ◽  
pp. F130-F137 ◽  
Author(s):  
Zhibo Gai ◽  
Lei Chu ◽  
Christian Hiller ◽  
Denis Arsenijevic ◽  
Carlos A. Penno ◽  
...  
Keyword(s):  
Renal Failure ◽  
Bile Acid ◽  
Chronic Renal Failure ◽  
Plasma Cholesterol ◽  
Experimental Studies ◽  
Control Group ◽  
Early Event ◽  
Minor Role ◽  
Serum Bile Acid ◽  
Protein Levels

Although the kidney is believed to play a minor role in bile acid (BA) excretion, chronic renal failure (CRF) has been reported to be associated with increased serum bile acid levels and alterations in BA homeostasis. The mechanisms for elevated BA levels are poorly understood in both clinical and experimental studies. This study was designed to examine the effects of naturally progressing CRF of longer duration on the hepatic and renal mRNA and protein levels of the BA-synthesizing enzyme Cyp7a1 and the BA transporters Ntcp, Bsep, Mrp3, Ost-α, and Ost-β. Sprague-Dawley rats were randomized to the CRF group (⅚ nephrectomy) or to the sham-operated control group and were analyzed 8 wk after surgery. Results obtained in the CRF rats were compared with those obtained in rats that had undergone uninephrectomy (UNX). The CRF group exhibited significantly increased plasma cholesterol and BA concentrations. Hepatic Cyp7a1 mRNA and protein levels were almost identical in the two groups. Hepatic Mrp3, Ost-α, and Ost-β expression was increased, suggesting increased basolateral efflux of bile acids into the blood. However, no such changes in BA transporter expression were observed in the remnant kidney. In UNX rats, similar changes in plasma BA levels and in the expression of BA transporters were found. We hypothesize that the increase in plasma BA is an early event in the progression of CRF and is caused by increased efflux across the basolateral hepatocyte membrane.

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