Cholesterol Absorption In Rats Research Articles

Long term effects on human plasma lipoproteins of a formulation enriched in butter milk polar lipid

BackgroundSphingolipids (SL), in particular sphingomyelin (SM) are important components of milk fat polar lipids. Dietary SM inhibits cholesterol absorption in rats (Nyberg et al. J Nutr Biochem. 2000) and SLs decrease both cholesterol and TG concentrations in lipid- and cholesterol fed APOE*3Leiden mice (Duivenvoorden et al. Am J Clin Nutr. 2006). This human study examines effects of a butter milk formulation enriched in milk fat globule membrane material, and thereby in SLs, on blood lipids in healthy volunteers. In a four week parallel group study with 33 men and 15 women we examined the effects of an SL-enriched butter milk formulation (A) and an equivalent control formulation (B) on plasma lipid levels. Plasma concentrations of HDL and LDL cholesterol, triacylglycerols (TG), apolipoproteins AI and B, and lipoprotein (a) were measured. The daily dose of SL in A was 975 mg of which 700 mg was SM. The participants registered food and drink intake four days before introducing the test formula and the last four days of the test period.ResultsA daily increase of SL intake did not significantly influence fasting plasma lipids or lipoproteins. In group B TG, cholesterol, LDL, HDL and apolipoprotein B concentrations increased, however, but not in group A after four weeks. The difference in LDL cholesterol was seen primarily in women and difference in TG primarily in men. No significant side effects were observed.ConclusionThe study did not show any significant decrease on plasma lipids or lipoprotein levels of an SL-enriched formulation containing 2-3 times more SL than the normal dietary intake on cholesterol, other plasma lipids or on energy intake. The formulation A may, however, have counteracted the trend towards increased blood lipid concentrations caused by increased energy intake that was seen with the B formulation.

Effects of Various Dietary Arginine and Lysine Concentrations on Plasma and Liver Cholesterol Concentrations in Rats

Background: It has been hypothesized that the arginine:lysine ratio of dietary proteins influences cholesterol concentrations in plasma and liver of men and animals. This study was performed to test this hypothesis in rats by using diets with various concentrations of arginine and lysine, differing in their arginine:lysine ratios. Methods: Two experiments with growing rats were performed, some of which received diets containing 4.5, 9 or 18 g arginine/kg and 9 or 18 g lysine/kg, respectively, for a period of 21 days. In the first experiment, a cholesterol-free diet was used; in the second experiment, a diet supplemented with cholesterol and sodium cholate as hypercholesterolaemic compounds was used. Results: In experiment 1, increasing the arginine concentration lowered HDL and plasma cholesterol concentration; however, cholesterol concentrations in liver, LDL and VLDL remained unchanged. In experiment 2, increasing the arginine concentration lowered HDL cholesterol and increased liver cholesterol (p < 0.05); cholesterol concentrations in plasma, LDL and VLDL remained unchanged. The only effect of the dietary lysine concentration concerned the effect on VLDL and liver cholesterol concentration, which were both lower in rats fed the diets with 18 g lysine/kg than in those fed the diets with 9 g lysine/kg (p < 0.05). Varying the dietary arginine:lysine ratio between 0.25 and 2.0 had no influence on cholesterol concentration in LDL and VLDL in both experiments; HDL cholesterol concentration was lowered by increasing this ratio (p < 0.05). Conclusion: The present study does not support the hypothesis that an increase in the dietary arginine:lysine ratio causes hypocholesterolaemic effects in rats.

Dietary pea protein stimulates bile acid excretion and lowers hepatic cholesterol concentration in rats.

It has been shown that some dietary plant proteins beneficially influence lipid metabolism in animals. The effect of pea protein in this respect however has not yet been investigated. Therefore, we studied the effect of purified pea protein on the lipid metabolism in rats. Twenty-four rats received diets with either 200 g/kg of casein or purified pea protein for 16 days. Concentrations of triacylglycerols in liver, plasma and lipoproteins did not differ between both groups of rats. However, rats fed the pea protein diet had a lower concentration of total cholesterol in the liver and the very low density lipoproteins (VLDL) fraction than rats fed the casein diet (p < 0.05); cholesterol concentration in plasma, low density lipoproteins (LDL) and high density lipoproteins (HDL) did not differ between both groups. Rats fed pea protein moreover had an increased mRNA concentration of cholesterol-7alpha-hydroxylase in the liver and an increased amount of bile acids excreted via faeces compared with rats fed casein (p < 0.05). Concomitantly, mRNA concentrations of sterol regulatory element-binding protein (SREBP)-2 and its target genes 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and LDL receptor in the liver were increased in rats fed pea protein (p < 0.05). The data of this study suggests that pea protein stimulates formation and excretion of bile acids, which leads to a reduced hepatic cholesterol concentration and a reduced secretion of cholesterol via VLDL. An increased gene expression of SREBP-2 and its target genes HMG-CoA reductase and LDL receptor may be a means to compensate for the increased loss of cholesterol for bile acid synthesis.

2-Azetidinone derivatives: Design, synthesis and evaluation of cholesterol absorption inhibitors

Fourteen new derivatives of the 2-azetidinone cholesterol absorption inhibitors have been synthesized, and three of them were enantiomerically pure. All the new compounds were evaluated for their activity to inhibit cholesterol absorption in rats, and most of them showed comparable effects in lowering the levels of total cholesterol in the serum.

Hypocholesterolemic and Anti‐Obesity Effects of Saponins from Platycodon grandiflorum in Hamsters Fed Atherogenic Diets

Platycodins, a group of saponin glycosides from Platycodon grandiflorum, are believed to possess anti-obesity and cholesterol-lowering properties. The aim of the present study was to investigate whether dietary platycodins affect plasma, hepatic, or fecal cholesterol concentrations, as well as cholesterol absorption and fractional synthesis rates in a dose-dependent manner. Golden Syrian hamsters (n= 45) were fed atherogenic (0.25% cholesterol) diets enriched with platycodins in the forms of either aqueous extracts (containing 0.3% to 0.5% of platycodins of diet mass) or crude saponins fractions (containing 0.9% to 1.0% of platycodins of diet mass) for 28 d. [3, 4](-13)C-cholesterol and (2)H2O tracers were administered on days 26 and 28 to assess cholesterol absorption and biosynthesis, respectively. After platycodin intervention, total cholesterol concentrations in plasma and liver were reduced (P < 0.05) by 13% to 28% and 41% to 79%, respectively, whereas cholesterol concentrations in feces were increased (P < 0.05) up to 2.5-fold compared to controls. Platycodin feeding increased (P < 0.001) cholesterol absorption up to 60%, but not cholesterol synthesis. These results suggest that platycodin-enriched diets can lower circulating and whole body cholesterol contents, and thus reduce the risk of cardiovascular diseases through mechanisms independent from cholesterol absorption or synthesis.

Association between non-responsiveness to plant sterol intervention and polymorphisms in cholesterol metabolism genes: a case-control study

Plant sterol (PS) consumption decreases low-density lipoprotein cholesterol (LDL-C) levels; however, high variability of responsiveness of lipid levels to PS intervention has been observed. We hypothesized that common single-nucleotide polymorphisms (SNPs) in the genes for the ATP binding cassette proteins G5 (ABCG5) and G8 (ABCG8), Niemann-Pick C1-like 1 (NPC1L1), or other proteins of the cholesterol pathway, would underline inter-individual variations in response to PS. Twenty-six hyperlipidemic subjects completed a randomized trial of 3 PS phases and a control phase. Three non-responders were identified who failed on 3 consecutive occasions to decrease either total cholesterol or LDL-C level vs. control. It was observed that after 3 PS phases compared with a control phase, cholesterol absorption changed to a lesser degree (-7.7% +/- 10.8%) in the non-responders than in the top 3 responders (-22.1% +/- 8.8%); however, cholesterol synthesis rates did not differ between sub-groups. No common polymorphisms in ABCG8, ABCG5, or NPC1L1 were demonstrated between the 3 top responders and the non-responders. Yet, 1 non-responsive subject did demonstrate a rare SNP in NPC1L1. Results indicate PS intake did not decrease cholesterol absorption rates to the same degree in certain subjects, possibly clarifying the inter-individual variability in the cholesterol-lowering effect; hence, this work should be expanded.

Efficacy of plant sterols in novel matrices on blood lipid profiles: medium-chain triglycerides and low-fat products consumed with or without a meal

Cardiovascular disease (CVD) risk can be lowered by introduction of plant sterols (PSs) to the diet, since PSs have been shown to reduce low-density lipoprotein cholesterol (LDL-C). Given that the efficacy of PSs as cholesterol-lowering agents depends on their appropriate solubilization, the cholesterol-lowering efficacy of PSs in non-traditional matrices needs to be determined. The primary aim of this thesis was to examine the consumption of PSs (i) in an oil that is rich in medium-chain triglycerides (MCTs) or (ii) low-fat yogurt with or without a meal, on changes in lipid parameters. Additional objectives were to assess the effects of MCTs with PSs on body composition and energetics, to compare the effects of PSs in a low-fat matrix consumed with or without a meal on cholesterol synthesis, to evaluate the risks of PSs in a low-fat matrix on blood levels of carotenoids and fat-soluble vitamins, and to investigate the relationship between the response to PSs, cholesterol kinetics, and genotyping. For this purpose, two randomized, controlled, crossover feeding trials were conducted. First, 23 overweight, hyperlipidemic men consumed PSs in MCTs or an olive oil control for 6 weeks each. In the second trial, 26 hyperlipidemic subjects consumed a placebo yogurt, a PS-enriched yogurt consumed with a meal, or afternoon PS-enriched yogurt as a snack for 4 weeks each. PSs, mixed within an MCT matrix, lowers plasma total cholesterol (TC) and LDL-C without changing the high-density lipoprotein cholesterol concentrations. However, no changes in body composition or energetics were observed. Second, a PS-enriched low-fat yogurt as a snack lowered TC, along with a lowering trend in LDL-C, to a greater extent than when consumed with a meal without any risk of deficiency in fat-soluble antioxidants. An increase in cholesterol biosynthesis was also observed in both PS phases compared with the control phase. In addition, 3 subjects who were non-responsive to PS intervention and had higher cholesterol absorption rates were observed; however, no recognizable pattern of genetic polymorphism was detected. Overall, these novel matrices for PS incorporation consumed with or between meals may be an effective way of decreasing the risk of CVD; however, some individuals respond better to PS intervention.

Enteral capsaicin lowers the lymphatic absorption of cholesterol (CH) in rats

Capsaicin has been shown to decrease serum CH and fat in rats. This study was conducted to examine if luminal infusion of capsaicin would affect the lymphatic absorption of CH and fat in rats. Adult male rats with lymph cannulae were infused intraduodenally at 3.0 mL/h for 8 h with a lipid emulsion consisting of 20.7 μmol CH labeled with 14C (14C‐CH), 452 μmol triolein (oleic acid, OA), and 3.1 μmol α‐tocopherol (αTP), and 396.0 ?mol Na‐taurocholate without (control) or with 5.0 mg capsaicin in 24 mL PBS buffer (pH, 6.3). Lymph was collected hourly for 8 h and lymph 14C‐radioactivity was determined. No significant difference was observed in lymph flow (17.8 ± 3.2 mL/8 h in capsaicin vs. 15.1 ± 1.8 mL in control). However, the lymphatic absorption of 14C‐CH for 8 h was significantly lower in rats infused with capsaicin (29.8 ± 1.0% dose) than in those infused with the lipid emulsion alone (39.1 ± 3.9%). The results provide evidence that luminal capsaicin reduces the intestinal absorption of CH in rats. The mechanism(s) by which capsaicin reduces CH absorption remains to be determined.

Comparison of Effects of Dietary Unesterified and Esterified Plant Sterols on Cholesterol Absorption in Rats

Effects of dietary unesterified plant sterols and plant sterol oleates and stearates on absorption and metabolism of cholesterol were compared in rats fed a cholesterol-supplemented diet. Fecal excretion of neutral steroids (cholesterol plus coprostanol) in rats fed unesterified plant sterols or plant sterol oleates was significantly higher than in those fed the control diet or plant sterol stearates. Deposition of cholesterol in the liver was significantly lower in rats fed unesterified plant sterols or plant sterol oleates than in those fed the control diet or plant sterol stearates. No significant difference was observed in fecal excretion of cholesterol plus coprostanol and hepatic cholesterol concentration between unesterified plant sterols and plant sterol oleates. Unesterified plant sterols were significantly more effective to reduce lymphatic recovery of radiolabeled cholesterol given to the stomach than plant sterol oleates. Although our observations suggest a possibility that unesterified plant sterols are potentially more effective to inhibit cholesterol absorption than plant sterol oleates in rats, difference in the activity is substantially small between these two forms of plant sterols.

Cholesterol metabolism and body composition in women: the effects of moderate weight loss

To determine how moderate weight loss protocol through diet and exercise may affect changes in body composition, to determine the effects of weight loss on cholesterol metabolism and to examine the relationship between cholesterol metabolism and changes in body composition. Thirty-five otherwise healthy, hypercholesterolemic women completed a 24-week weight loss study. A 20% decrease in energy intake through diet and a 10% increase in energy expenditure by exercise were combined with motivational strategies to encourage weight loss. The diet was self-selected and comprised of 50-60% carbohydrates, 20% protein and <30% fat. Participants lost an average of 11.7+/-2.5 kg (P<0.001). Whole body and regional losses in tissue mass occurred after weight loss. After weight loss, cholesterol fractional synthesis rate (FSR) decreased (P=0.003) 3.86+/-9.33%, whereas rates of cholesterol absorption and turnover did not change (3.31+/-19.4%, P=0.32 and -0.01+/-6.20%, P=0.75, respectively). Changes in cholesterol turnover were positively correlated (r=0.44, P=0.01) with changes in FSR. Reductions in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were predictive (beta=-5.04, r=0.38; P=0.03, and beta=-147, r=0.40; P=0.03, respectively) of increases in cholesterol turnover. Losses in skeletal muscle (SM) and upper-body SM predicted (beta=6.82, r=0.36; P=0.04 and beta=14.7, r=0.41; P=0.01, respectively) decreases in cholesterol absorption. Decreases in cholesterol synthesis after moderate weight loss are not compensated for by changes in cholesterol absorption or turnover. Changes in regional body composition were associated with variations in cholesterol metabolism. Understanding how weight loss affects cholesterol metabolism will help identify more effective treatment routes for overweight individuals undergoing weight loss resulting in earlier and more intensive therapy for the associated dyslipidemia.

Effect of melatonin on cholesterol absorption in rats

This study evaluated the influence of melatonin on cholesterol absorption in rats fed on high cholesterol diet (HCD). HCD induced a remarkable increase in hepatic and plasma total cholesterol, plasma very low density lipoprotein (VLDL) and low density lipoprotein (LDL) cholesterol, a decrease in high density lipoprotein (HDL) cholesterol and an elevation in triacylglyceride (TG) levels in plasma and in the liver. Melatonin suspension (10 mg/kg), specially prepared for this purpose, cholestyramine (230 mg/kg) and ezetimibe (145 microg/kg) were administered orally to the rats fed HCD for 30 days. Melatonin significantly reduced cholesterol absorption in rats fed on HCD and caused significant decreases in total cholesterol, TG, VLDL- and LDL-cholesterol in the plasma and contents of cholesterol and TG in the liver. The level of HDL cholesterol was significantly increased after melatonin. These results suggested that inhibition of cholesterol absorption caused by melatonin could be a mechanism contributing to the positive changes in plasma cholesterol, lipoprotein profile and the lipid contents in the liver.

Effect of Endurance Exercise Training on Markers of Cholesterol Absorption and Synthesis

Recent studies have shown that circulating levels of plant sterols (campesterol and sitosterol) are markers of cholesterol absorption, while lathosterol, a precursor in the cholesterol synthetic pathway, is a marker for whole body cholesterol synthesis. Endurance exercise training is known to have favorable effects on plasma cholesterol levels, but it is not known if this is mediated in part by changes in rates of cholesterol absorption or synthesis. To examine this, we measured circulating levels of campesterol, sitosterol, and lathosterol by GC/mass spectroscopy from plasma samples of 30 sedentary subjects (20 women, 10 men, average age = 59) before and after 6 months of endurance exercise training. There was no change in sitosterol or lathosterol levels in response to the exercise training intervention. However, there was a trend for an increase in plasma campesterol levels of 20% following the intervention (p = 0.07). Other changes in lipids included the following: there was no change in total or LDL-C levels in response to the exercise intervention; however, HDL-C and the HDL2-C subfraction increased 4.0mg/dL and 2.2mg/dL, respectively (p < .01), and total triglyceride levels decreased by 20mg/dL (p < 0.001). The increase in plasma campesterol indicates that endurance exercise training may have a significant impact on rates of cholesterol absorption. Reduced levels of cholesterol absorption have been linked to the development of the “metabolic syndrome.” As a result, this exercise induced increase in campesterol levels may suggest a previously unrecognized benefit of exercise training on cholesterol metabolism.

Selective Compensatory Induction of Hepatic HMG-CoA Reductase in Response to Inhibition of Cholesterol Absorption

The effect of the potent inhibitor of cholesterol absorption, ezetimibe, on serum cholesterol levels was tested in diabetic and thyroidectomized male Sprague-Dawley rats. Feeding diets supplemented with 1% cholesterol to the diabetic rats raised serum cholesterol levels from 132 to 514 mg/dl while decreasing hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase protein and mRNA levels. Addition of 10 mg/kg/day of ezetimibe to the diets of these animals lowered the serum cholesterol level to 90 mg/dl and produced a large compensatory increase in hepatic HMG-CoA reductase protein without significantly increasing mRNA levels, indicating a post-transcriptional effect. Hepatic LDL receptor protein levels in these diabetic rats were unaffected by ezetimibe treatment. In contrast, ezetimibe treatment of these young normal Sprague-Dawley rats, known to express high levels of hepatic HMG-CoA reductase, did not lower serum cholesterol levels. In thyroidectomized rats, dietary cholesterol increased serum cholesterol levels from 116 to 135 mg/dl and ezetimibe treatment lowered these elevated cholesterol levels to 85 mg/dl. Cholesterol feeding of thyroidectomized rats severely reduced hepatic HMG-CoA reductase protein, while ezetimibe treatment restored reductase protein to normal levels. Again, hepatic LDL receptor protein levels were unaffected by ezetimibe treatment of cholesterol-fed thyroidectomized rats. The data demonstrate that the cholesterol absorption inhibitor ezetimibe profoundly lowers serum cholesterol levels in animals expressing very low rates of hepatic cholesterol synthesis and produces large compensatory increases in hepatic HMG-CoA reductase expression without significantly affecting expression of hepatic LDL receptors. This indicates that ezetimibe should be most effective in lowering serum cholesterol levels in people with low rates of cholesterol synthesis/high rates of cholesterol absorption.

Effect of dietary methionine on plasma and liver cholesterol concentrations in rats and expression of hepatic genes involved in cholesterol metabolism

Methionine has been shown to increase plasma cholesterol in animals. In the present study, mechanisms were investigated by which methionine could alter cholesterol metabolism. In the first experiment, forty growing rats were fed four casein-based diets differing in methionine content (2.6, 3.5, 4.5 or 6.0 g/kg) for 14 d. In the second experiment, isolated rat hepatocytes were incubated in media supplemented with 50, 100 or 200 micromol/l methionine. Dietary methionine tended to increase plasma homocysteine concentrations in the rats (P=0.058). A weak positive correlation between circulating homocysteine and plasma cholesterol was observed (R2 0.27, P<0.01). Rats fed 3.5 g/kg or more of methionine had higher concentrations of cholesterol in their plasma, in lipoprotein fractions of density (rho; kg/l) 1.006<rho<1.063 and rho>1.063, and in liver than rats fed 2.6 g/kg methionine. Rats fed 6 g/kg methionine had a higher hepatic expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol-7alpha-hydroxylase than rats fed less methionine. The phosphatidylcholine:phosphatidylethanolamine ratio in rat liver increased with rising dietary methionine concentration; the relative mRNA concentrations of phosphatidylethanolamine N-methyltransferase and cystathionine beta-synthase remained unaffected. Hepatocytes incubated in media supplemented with 100 or 200 micromol/l methionine had a higher cholesterol synthesis than hepatocytes incubated in a medium supplemented with 50 micromol/l methionine; the LDL uptake in hepatocytes was independent of the methionine concentration of the medium. In conclusion, the present study suggests that dietary methionine induces hypercholesterolaemia at least in part via an enhanced hepatic cholesterol synthesis.

Sequence variation in NPC1L1 and association with improved LDL-cholesterol lowering in response to ezetimibe treatment

Niemann-Pick C1-like 1 (NPC1L1) is an intestinal cholesterol transporter and the molecular target of ezetimibe, a cholesterol absorption inhibitor demonstrated to reduce LDL-cholesterol (LDL-C) both as monotherapy and when co-administered with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). Interestingly, significant interindividual variability has been observed for rates of intestinal cholesterol absorption and LDL-C reductions at both baseline and post ezetimibe treatment. To test the hypothesis that genetic variation in NPC1L1 could influence the LDL-C response to ezetimibe, we performed extensive resequencing of the gene in 375 apparently healthy individuals and genotyped hypercholesterolemic patients from clinical trial cohorts. No association was observed between NPC1L1 single-nucleotide polymorphism and baseline cholesterol. However, significant associations to LDL-C response to treatment with ezetimibe were observed in patients treated with ezetimibe in two large clinical trials. Our data demonstrate that DNA sequence variants in NPC1L1 are associated with an improvement in response to ezetimibe pharmacotherapy and suggest that detailed analysis of genetic variability in clinical trial cohorts can lead to improved understanding of factors contributing to variable drug response.

Effect of silymarin and its polyphenolic fraction on cholesterol absorption in rats

This study evaluated the influence of silymarin (SM) and polyphenolic fraction (PF) of silymarin on cholesterol absorption in rats fed on high cholesterol diet (HCD). HCD induced a remarkable increase in hepatic, plasma, VLDL and LDL cholesterol, a decrease in HDL cholesterol and an elevation in triacylglycerol (TAG) levels in plasma, VLDL and in the liver. SM and PF were administered as dietary supplements (1.0%) in HCD for 18 days. Intestinal cholesterol absorption was measured by dual-isotope plasma ratio method, which calculates percent of cholesterol absorption from the ratio of two labelled cholesterol doses, one given intragastrically ( 14C) and one intravenously ( 3H). Silymarin and PF significantly reduced cholesterol absorption in rats fed on HCD and caused significant decreases in plasma and VLDL cholesterol and content of cholesterol and TAG in the liver. The level of HDL cholesterol was significantly increased after silymarin, but not after administration of PF. The levels of TAG in plasma and VLDL were not affected by either silymarin or PF. These results suggest that the inhibition of cholesterol absorption caused by silymarin and its polyphenolic fraction could be a mechanism contributing to the positive changes in plasma cholesterol lipoprotein profile and in lipid content in liver.

The Selective Estrogen Receptor Modulator Acolbifene Reduces Cholesterolemia Independently of Its Anorectic Action in Control and Cholesterol-Fed Rats

The cancer-preventing selective estrogen receptor modulator (SERM) acolbifene (ACOL) exerts a potent and pure antiestrogenic action in the mammary gland and uterus, yet it displays beneficial, estrogen-like actions on energy and lipid metabolism in rodents. The compound reduces food intake and strongly decreases cholesterolemia in rats fed a cholesterol-free diet. This study was designed to establish whether the anorectic effect of ACOL is involved in its cholesterol-lowering action, and whether the compound retains its ability to lower cholesterol concentrations in rats with diet-induced hypercholesterolemia. Female rats were fed a purified diet devoid of cholesterol (reference diet) or containing 2% cholesterol (C-diet); they were either not treated or treated daily with ACOL or not treated and pair-fed to the ACOL-treated rats. The C-diet did not affect food intake or weight and fat gains. ACOL reduced food intake (16%) and weight gain (45%, mainly fat) similarly in both dietary cohorts. ACOL, but not pair feeding, reduced cholesterolemia by 33% in rats fed the reference diet. As expected, the C-diet raised serum total cholesterol almost 3-fold and this increase was largely prevented by ACOL but not by pair feeding. Cholesterol was reduced by ACOL, mainly in the HDL fraction, in rats fed the reference diet, but only in the non-HDL fraction in those fed the C-diet. In livers of rats fed the reference diet, ACOL, but not pair feeding, increased protein abundance of the scavenger receptor, class B, type 1, and the LDL receptor, thought to be involved in ACOL-mediated cholesterol lowering. These findings demonstrate that the potent hypocholesterolemic action of ACOL is independent of the concomitant reduction in food intake and fat accretion, and that such action occurs in rats with overt diet-induced hypercholesterolemia.

Soy protein reduces hepatic lipotoxicity in hyperinsulinemic obese Zucker fa/fa rats

Hepatic steatosis is commonly present during the development of insulin resistance, and it is a clear sign of lipotoxicity attributable in part to an accelerated lipogenesis. There is evidence that a soy protein diet prevents the overexpression of hepatic sterol-regulatory element binding protein-1 (SREBP-1), decreasing lipid accumulation. Therefore, the aim of the present work was to study whether a soy protein diet may prevent the development of fatty liver through the regulation of transcription factors involved in lipid metabolism in hyperinsulinemic and hyperleptinemic Zucker obese fa/fa rats. Serum and hepatic cholesterol and triglyceride levels, as well as VLDL-triglyceride and LDL-cholesterol, were significantly lower in rats fed soy protein than in rats fed a casein diet for 160 days. The reduction in hepatic cholesterol was associated with a low expression of liver X receptor-alpha and its target genes, 7-alpha hydroxylase and ABCA1. Soy protein also decreased the expression of SREBP-1 and several of its target genes, FAS, stearoyl-CoA desaturase-1, and delta5 and delta6 desaturases, decreasing lipogenesis even in the presence of hyperinsulinemia. Reduction in SREBP-1 was not associated with the presence of soy isoflavones. Finally, soy protein reduced SREBP-1 expression in adipocytes, preventing hypertrophy, which also helps prevent the development of hepatic lipotoxicity.

Plant sterols are efficacious in lowering plasma LDL and non-HDL cholesterol in hypercholesterolemic type 2 diabetic and nondiabetic persons2–3

Because of hyperglycemia and hyperinsulinemia, diabetic persons have higher cholesterol synthesis and lower cholesterol absorption rates than do nondiabetic persons. Differences in plant sterol efficacy between diabetic and nondiabetic persons have not been examined. The objective was to compare the degree of response of plasma lipid concentrations and glycemic control to plant sterol consumption in a controlled diet between hypercholesterolemic type 2 diabetic and nondiabetic subjects. Fifteen nondiabetic subjects and 14 diabetic subjects participated in a double-blinded, randomized, crossover, placebo-controlled feeding trial. The diet included 1.8 g/d of either plant sterols or cornstarch placebo over 21 d, separated by a 28-d washout period. Plant sterol consumption significantly reduced (P < 0.05) LDL-cholesterol concentrations from baseline in both nondiabetic and diabetic subjects by 15.1% and 26.8%, respectively. The diabetic subjects had significantly (P < 0.05) lower absolute concentrations of total cholesterol after treatment than did the nondiabetic subjects; however, there was no significant difference in the percentage change from the beginning to the end of the trial. There was also a significant decrease (P < 0.05) in absolute non-HDL-cholesterol concentrations after treatment in both groups. The results showed that plant sterols are efficacious in lowering LDL cholesterol and non-HDL cholesterol in both diabetic and nondiabetic persons. Plant sterol consumption may exist as a dietary management strategy for hypercholesterolemia in persons with type 2 diabetes.

Molecular mechanisms of cholesterol absorption and transport in the intestine

Many enzymes and transport proteins participate in cholesterol absorption. This review summarizes recent results on several proteins that are important for each step of the cholesterol absorption pathway, including the important roles of: (i) pancreatic triglyceride lipase (PTL), carboxyl ester lipase (CEL), and ileal bile acid transporter in determining the rate of cholesterol absorption; (ii) ATP binding cassette (ABC) transporters and the Niemann-Pick C-1 like-1 (NPC1L1) protein as intestinal membrane gatekeepers for cholesterol efflux and influx; and (iii) intracellular membrane vesicles and transport proteins in lipid trafficking through intracellular compartments prior to lipoprotein assembly and secretion to plasma circulation.