Choosing hamsters but not rats as a model for studying plasma cholesterol‐lowering activity of functional foods

Rats and hamsters are commonly used rodents to test the efficacy of cholesterol‐lowering functional foods. In general, a diet containing 1% cholesterol for rats whereas a diet containing 0.1% cholesterol for hamsters is used to induce the hypercholesterolemia. The present study was carried out to compare hamsters with rats as a hypercholesterolemia model. Golden Syrian hamsters and Sprague Dawley rats were randomly divided into four groups and fed one of the four diets containing 0–0.9% cholesterol. Results demonstrated that serum total cholesterol (TC) in hamsters was raised 73–81% higher than that in rats fed the same cholesterol diets. Unlike rats in which HDL‐C accounted very little for serum TC, the lipoprotein profile in hamsters was closer to that in humans. We investigated interaction of higher cholesterol diets with 3‐hydroxy‐3‐methylglutary‐CoA (HMG‐CoA) reductase, low‐density lipoprotein receptor (LDL‐R) and cholesterol‐7α‐hydroxylase (CYP7A1), sterol regulatory element binding protein‐2 (SREBP‐2), and liver X receptor (LXR‐α). Results showed hamsters and rats metabolized cholesterol differently. In view that hamsters synthesize and excrete cholesterol and bile acids in a manner similar to that in humans, it is concluded that hamsters but not rats shall be chosen as a model to study efficacy of cholesterol‐lowering functional foods.     

Feeding Tomatoes to Hamsters Reduces their Plasma Low-density Lipoprotein Cholesterol and Triglycerides

Hamsters were fed semipurified diets containing green or red freeze‐dried tomato powders. Compared to the control diet devoid of tomatoes, a 59% and 44% reduction low‐density lipoprotein (LDL) cholesterol was induced by both the green and red tomatoes, respectively. The corresponding reductions in very low‐density lipoproteins (VLDL) were 45% and 35% and in plasma triglyceride concentrations 47% and 31%, respectively. Plasma levels of high‐density lipoproteins (HDL) were unaffected. Fecal deoxycholic and lithocholic acid concentrations of hamsters on tomato diets were higher than those on control diets. Possible contributions of major components of green and red tomatoes to these beneficial effects are discussed.     

Effect of high-fat diets supplemented with okara soybean by-product on lipid profiles of plasma,liver and faeces in Syrian hamsters

The main components of okara, a by-product from soybean, are dietary fibre and protein. In this study we fed okara based diets with different amounts of fibre, protein and isoflavones to determine their effect on the lipid profile in the plasma, liver and faeces of an animal model. Male golden Syrian hamsters were fed high-fat diets supplemented with okara for 3 weeks. The supplemented diets contained 13% or 20% of okara fibre (OK-13 and OK-20), low-protein okara with 13% of fibre (OK1-13), and isoflavone-free okara with 13% of fibre (OK2-13). Okara supplemented diets did not produce significant differences in the feed intake or body weight gain (p > 0.05). The plasma levels of triglycerides, VLDL- plus LDL cholesterol and total cholesterol in hamsters fed OK-20 decreased significantly (p < 0.05) with respect to the 20% control group (C-20). However, no significant differences (p > 0.05) were found in LDL- and HDL-cholesterol plasma levels in all experiments. Total lipids, triglycerides, total and esterified cholesterol concentrations in liver were reduced by OK-20 diet. Regarding the hamsters fed OK-13 diets, the mean values of the total lipid, triglyceride and cholesterol in the plasma and liver decreased as compared to the control (C-13), but the differences were not statistically significant. All of the okara diets assayed increased the faecal excretion of total lipids, triglycerides, free cholesterol and total nitrogen (p < 0.05) compared to their respective controls. Our results suggest that the main components of okara, dietary fibre and protein, could be related with the total lipids and cholesterol decrease in the plasma and liver, as well as with the faecal output increase in high-fat fed hamsters. Okara might play an interesting role in the prevention of hyperlipidemia and could be used as a natural ingredient or supplement for functional food preparation.     

Sugar beet pulp and apple pomace dietary fibers improve lipid metabolism in rats fed cholesterol

The effect of diets supplemented with sugar beet pulp fiber (SBP, 10%) and apple pomace fiber (AP, 10%) on lipids and lipids peroxides was investigated in 60 male Wistar rats. The rats were divided into six groups of 10 and adapted to cholesterol-free or 0.3% cholesterol diets. The basal diet (BD) contained wheat meal, barley meal, wheat hulls, meat-bone meal, barley sprouts, skimmed milk, fodder yeast, mineral and vitamin mixtures. The Control group (Control) consumed BD only. To the BD were added 3 g/kg cholesterol (Chol), 100 g/kg dry sugar beet pulp fiber (SBP), both 100 g/kg sugar beet pulp fiber and 3 g/kg cholesterol (SBP+Chol), 100 g/kg apple pomace fiber (AP), both 100 g/kg apple pomace fiber and 3 g/kg cholesterol (AP+Chol). The experiment lasted 40 days. Plasma total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), triglycerides (TG), total phospholipids (TPH), HDL phospholipids (HDL-PH), lipid peroxides (LP) and liver TC concentration were measured. Groups did not differ before the experiment. In the Chol+SBP and the Chol+AP vs. Chol group the sugar beet pulp and apple pomace dietary fiber supplemented diet significantly (P<0.05) hindered the rise of plasma lipids: (a) TC−2.97 vs. 3.69 mmol/l, −20% and 3.01 vs 3.69 mmol/l, −18.4%, respectively; (b) LDL-C −1.36 vs. 2.02 mmol/l, −32.6% and 1.39 vs. 2.02 mmol/l, −31.2%, respectively; (c) TG −0.73 vs. 0.88 mmol/l, and 0.75 vs. 0.88 mmol/l; −17 and −14.8%, respectively, and TC in liver (17.1 vs. 24.3 μmol/g, −29.6% and 17.9 v. 24.3 μmol/g, −26.3%, respectively. Sugar beet and apple pomace fiber-supplemented diets significantly hindered the decrease in HDL-PH (0.79 vs. 0.63 mmol/l, −25.3%, P<0.025 and 0.75 vs. 0.63 mmol/l, −19%, P<0.05, respectively) and decreased the level of TPH (1.34 vs. 1.74 mmol/l, −23%, P<0.005 and 1.37 vs. 1.74 mmol/l, −21.3%, P<0.01, respectively). Both sugar beet pulp fiber and apple pomace fiber, in rats fed the basal diet without cholesterol, did not significantly affect the variables measured. Neither sugar beet pulp fiber or apple pomace fiber-supplemented diets influenced the level of lipid peroxides. These results demonstrate that sugar beet pulp fiber and to a lesser degree apple pomace fiber possess hypolipidemic properties. This is more evident when sugar beet pulp fiber or apple pomace fiber are added to the diet of rats fed cholesterol. The hypolipidemic effects of both sugar beet pulp fiber and apple pomace fiber can be attributed to their water-soluble parts. The sugar beet pulp and apple pomace fibers have no antioxidant properties.     

Glycaemic responses and hypocholesterolaemic effects of high-amylose barley diets on broiler chicks

The glucose and lipid responses of barley diets were investigated with chicks based on either flour or red dog (RD) from each of three barley cultivars, Glacier, covered high-amylose Glacier (HAG) and hull-less high-amylose Glacier (HHAG), with two maize control diets. Mean time interval blood glucose levels were higher (P<0·05) for chicks fed uncooked barley flour or RD, compared with controls. Total and LDL plasma cholesterol were lower (P<0·05) for chicks fed the HAG and HHAG flour and all barley RD diets. HDL cholesterol values for chicks fed Glacier and HHAG flour and HHAG RD diets were higher than controls. The LDL/HDL cholesterol ratios for chicks fed HAG and HHAG flour and all barley RD diets were lower (P<0·05) than controls. Lower body weights were observed in all chickens fed barley diets. The results suggest that the soluble fibre, mainly β-glucan and starch structures, in barley may be responsible for the hypocholesterolaemic effect. © 1998 SCI.     

Effects of a black rice extract (Oryza sativa L. indica) on cholesterol levels and plasma lipid parameters in Wistar Kyoto rats

This study was designed to evaluate the efficacy of an anthocyanin pigmented rice (e.g. black rice) to mitigate the onset of hypercholesterolemia in rats-fed atherogenic diets. Male Wistar (n = 10/group) rats were fed with atherogenic diets containing 0.5% cholesterol in the presence and in the absence of bile salt (e.g. 0.05% cholic acid) along with a standardized black rice extract (BRE) (e.g. 3%, w/w). All animals were individually housed in stainless steel cages and fed with the experimental diets during a 12-h period for 10 weeks. Body weights of rats were measured every week of the experiment. After 10 weeks fed on experimental diets, rats were sacrificed and plasma total cholesterol, HDL and LDL cholesterol and triacylglycerols were measured immediately. The total cholesterol (TC) content in the liver, heart and aorta, and the concentration of triacylglycerol (TAG) were measured after lipid extraction using Folch method. Rats fed with 0.5% cholesterol containing diets which also included bile salt exhibited a considerably more severe hypercholesterolemia than counterparts fed diets containing only 0.5% cholesterol. The inclusion of the BRE in diets significantly (p < 0.05) decreased the level of TC, LDL–TC and TAG in plasma of rats-fed control diets that either contained or were absent in bile salt (p < 0.05). There were no differences in HDL-level. Liver crude lipids and total cholesterol levels were also significantly (p < 0.05) decreased in experimental groups relative to the control group in both experiments. Thus, supplementation of atherogenic experimental diets with BRE effectively decreased lipid levels in hypercholesterolemic rats. In lieu of the mixture of bioactive components present in BRE, it is possible that more than one mechanism underlying this reduction in lipids is involved.     

Plasma total,lipoprotein cholesterol,organs cholesterol and growth performance in rats fed dietary gum arabic

Thirty two male Wistar rats with initial body weight ranging from 45 to 55 g were randomly assigned to four dietary treatments. Rats were fed with ad libitum access diets containing 7.5% as cellulose or gum arabic with or without 1% added cholesterol for five weeks. Final body weight, body weight gain and feed efficiency ratio were comparable in all groups. Within cholesterol-fed groups, the cholesterol concentration of plasma was significantly lower in rats fed diet supplemented with gum arabic compared with those fed cellulose. Among cholesterol-fed groups, liver cholesterol was significantly higher in the group fed diet supplemented with gum arabic compared with those fed cellulose. In rats fed cholesterol-free diets, the cholesterol levels of plasma, LDL, HDL and liver were comparable.     

Taurine alleviates dyslipidemia and liver damage induced by a high-fat/cholesterol-dietary habit

Eight male hamsters per group were assigned randomly to one of the following diets: chow diet (Control); high-fat/cholesterol diet (HFCD); HFCD supplemented with 1% Tau (HFCD/1% Tau); HFCD supplemented with 2% Tau (HFCD/2% Tau). Tau supplementation improved (P < 0.05) serum lipids and cholesterol profile in the high-fat/cholesterol-dietary hamsters. Although hepatic cholesterol/triacylglycerol in the high-fat/cholesterol-dietary hamsters were not (P > 0.05) changed by Tau supplementation, faecal cholesterol and bile acid outputs were increased (P < 0.05). Two percent Tau supplementation unregulated (P < 0.05) HMG-CoA reductase and cholesterol 7-α hydroxylase (CYP7A1) expressions in the high-fat/cholesterol-dietary hamsters. Besides, Tau supplementation also increased (P < 0.05) LDL receptor mRNA expressions in high-fat/cholesterol-dietary hamsters. Tau supplementation also reduced serum GPT and GOT values and C-reactive protein (CRP) levels in the high-fat/cholesterol-dietary hamsters. Results clearly indicated that Tau could alleviate blood lipids and hepatic damage induced by a high-fat/cholesterol-dietary diet.     

Cholesterol‐Lowering Properties of Whole Cowpea Seed and Its Protein Isolate in Hamsters

ABSTRACT: Hypercholesterolemic hamsters were fed for 4 wk on diets rich in saturated fatty acids and cholesterol, differing only in protein source (20 %): casein (control group, HC), whole cowpea seed (HWS), and cowpea protein isolate (HPI). Hamsters fed on HWS and HPI presented significant reductions in plasma total cholesterol and non‐HDL cholesterol. HPI and HC presented similar protein digestibility, which were significantly higher than that of HWS. Animals fed on HWS presented significantly higher levels of bile acids and cholesterol in feces than did the animals fed on casein or HPI diets. Histological analyses of the liver showed that HC diet resulted in steatosis widely distributed throughout the hepatic lobule, while HWS and HPI diets promoted reductions in liver steatosis. The effectiveness of HWS for modulating lipid metabolism was greater than that of HPI, as measured by plasma cholesterol reduction and liver steatosis.     

FISH OIL WITH ESSENCE OF CHICKEN DECREASES SERUM AND HEPATIC TRIACYLGLYCEROL IN HAMSTERS FED AN ATHEROGENIC DIET

The aim of the present study was to investigate the effect of a mixture of dietary chicken essence and fish oil on possible lowering of blood and hepatic lipids in hamsters. Forty male hamsters were randomly divided into four groups and fed a chow diet, high fat/cholesterol diet (HFC), HFC diets containing 4% (HFC4) or 8% (HFC8) fish oil with essence of chicken for 42 days. The experimental diets contained 10% (w/w) fat. Hamsters fed HFC diets containing either 4 or 8% fish oil with essence of chicken showed significantly decreased serum triacylglycerols (TG) compared to hamsters fed HFC diets. In addition, hamsters fed HFC8 diets exhibited significantly reduced hepatic TG than those fed HFC diet. However, hamsters fed HFC4 or HFC8 diets significantly increased low density lipoprotein cholesterol (LDL-C) and decreased high density lipoprotein cholesterol (HDL-C) when compared with those on HFC diet. These results suggest that 4% (or more) fish oil with essence of chicken might significantly lower serum TG and hepatic TG in hamsters, but seem to increase serum cholesterol levels on HFC diets.     

Effects of highly purified sardine proteins on lipid peroxidation and reverse cholesterol transport in rats fed a cholesterol-rich diet

The effect of highly purified sardine proteins was compared with that of casein on serum and lipoproteins lipid peroxidation and reverse cholesterol transport. Lecithin:cholesterol acyltransferase (LCAT) activity, high density lipoproteins (HDL₂ and HDL₃) composition and serum lipid and lipoproteins peroxidation were determined in rats fed a cholesterol-rich diet. Hypercholesterolemic rats were divided into two groups fed diets enriched with cholesterol and containing 20% of highly purified sardine proteins (SPc) or casein (CASc) for 28 days. A control group was fed a standard diet (CAS). Compared with CAS and CASc, the thiobarbituric acid reactive substances (TBARS) concentrations of low density lipoprotein (LDL)–HDL₁ in SPc were 3.5- and 1.7-fold higher compared with casein diets. TBARS in HDL₂ and HDL₃ were, respectively, 2.3- and 1.6-fold lower in SPc compared with CASc. In SPc group, LCAT activity was higher compared to CASc and CAS (P < 0.05). Purified sardine proteins had no beneficial effects on LDL-cholesterol and lipid peroxidation. However, they reduced HDL oxidation and improved reverse cholesterol transport, in the hypercholesterolemic rat.     

Inhibitory effects of Hibiscus sabdariffa L extract on low‐density lipoprotein oxidation and anti‐hyperlipidemia in fructose‐fed and cholesterol‐fed rats

Hibiscus sabdariffa L extract (HSE) is an aqueous extract of Hibiscus sabdariffa L flowers that is used as a local soft drink and medical herb in Taiwan. Oxidation of low‐density lipoprotein (LDL) has been shown to increase the incidence of atherosclerosis. In this study, we determined the antioxidative activity of HSE on LDL oxidation by examining relative electrophoretic mobilities (REM) and thiobarbituric acid‐reactive substances (TBARS). The data revealed an inhibitory effect of HSE on Cu²⁺‐mediated REM and TBARS. HSE exhibited a remarkable ability to reduce cholesterol degradation and ApoB fragmentation. Overall, HSE showed a high potency to inhibit the production of oxidized LDL induced by copper and, specifically, to reduce serum triglycerides in high‐fructose diet (HFD) fed rats and serum cholesterol in high‐cholesterol diet (HCD) fed animals. The levels of LDL and the ratio of LDL‐cholesterol (LDL‐C) to HDL‐cholesterol (HDL‐C) were reduced by HSE in both hyperlipidaemia models. Based on these findings, we suggest that HSE may be used to inhibit LDL oxidation and to prevent various types of hyperlipidaemia in HFD‐ or HCD‐fed rats. Copyright © 2004 Society of Chemical Industry     

Intact pectin and its polygalacturonic acid regions have similar hypocholesterolemic properties in hybrid F1B hamsters

We fed cholesterol-enriched (0.1% w/w) semipurified diets containing 3% of lemon pectin or 3% of the polygalacturonic acid regions fraction (smooth regions fraction) of the lemon pectin to hybrid F1B hamsters for a period of 8 weeks. A control group was fed cellulose and a positive control group was fed psyllium. The feeding of the semipurified diets resulted in an increase of plasma cholesterol levels in all the dietary groups when compared with initial values. The hamsters fed the psyllium, pectin, or the polygalacturonic acid regions fraction had significantly (P < 0.05) lower plasma cholesterol levels than the cellulose fed group throughout the experimental period. Plasma cholesterol levels in the hamsters fed the psyllium, pectin, or polygalacturonic acid regions fraction were not significantly different. Liver cholesterol concentrations were also lower in the hamsters fed the psyllium, pectin, or the polygalacturonic acid regions fraction than in the hamsters fed the cellulose, but this effect reached statistical significance only in the hamsters fed the polygalacturonic acid regions fraction. The results of these studies suggest that the polygalacturonic acid regions of the pectin molecule is responsible for the cholesterol-lowering properties of the pectin.     

Hypocholesterimic effects of cold and hot extracted virgin coconut oil (VCO) in comparison to commercial coconut oil: Evidence from a male wistar albino rat model

The hypolipidemic effect of cold extracted virgin coconut oil (CEVCO) and hot extracted virgin coconut oil (HEVCO) compared to commercially available coconut oil (CCO) was studied using male wistar rats. Groups were designated as control, hypercholesterimic control (HC Control), HC+10% (CEVCO), HC+15% (CEVCO), HC+10% (HEVCO), HC+15% (HEVCO) and HC+15% (CCO). Control rats were fed a basal diet while other groups were initially fed a hypercholesterimic diet (2% cholesterol and 0.25% bile salts) for 15 days, then fed with CEVCO or HEVCO (both at 10% and 15% levels), and commercial coconut oil (15%) for 30 days. Total cholesterol and LDL cholesterol levels were significantly (p<0.05) decreased by approximately 25 and 40%, respectively, in the blood plasma, while HDL cholesterol increased significantly (p<0.05) by approximately 21% in HEVCO fed rats. Tissue cholesterol and triacylycerol (TAG) levels in both liver and heart tissues decreased significantly (p<0.05) in CEVCO and HEVCO fed animals, compared with CCO fed rats.     

Nutritional properties of fibre-rich barley products fed to broiler chickens

The chemical composition of roller-milled fractions of barley from a commercial plant was studied and a fraction rich in mixed-linked β-glucans selected. This fraction contained 560 g kg^?1 starch, 120 g kg^?1 crude protein, 170 g kg^?1 dietary fibre and 70 g kg^?1 mixed-linked β-glucans. An unprocessed, drum-dried or extrusion-cooked fraction was used as the major ingredient in diets for broiler chickens. The diets were fed with or without a supplementary fibre-degrading enzyme preparation in order to evaluate specifically the nutritional effects of the soluble dietary fibres. Processing significantly retarded growth, cumulative feed intake and feed conversion efficiency of the diets fed without enzyme supplementation, while the supplementation significantly improved all three parameters for each diet. Generally, processing decreased plasma triglycerides and total cholesterol and increased the ratio between high-density lipoproteins (HDL) and total cholesterol of chickens fed diets without enzyme supplementation. The enzyme supplementation increased the triglyceride and total cholesterol values and decreased the HDL/total cholesterol ratio, with more pronounced effects for chickens fed the processed diets.     

Carrot insoluble fiber-rich fraction lowers lipid and cholesterol absorption in hamsters

Potential effects of the insoluble fiber-rich fractions (IFRF) prepared from carrot pomace on lipid and cholesterol absorption in hamsters were investigated. As compared with the cellulose-added and fiber-free diets, IFRF diet significantly (P<0.05) lowered the levels of serum triglyceride, serum total cholesterol, and liver cholesterol, and meanwhile resulted in a significantly (P<0.05) higher HDL:total cholesterol ratio as well as higher levels of fecal lipids, cholesterol, and bile acids. Significant correlations were observed among the levels of serum triglyceride, serum total cholesterol, liver cholesterol, fecal lipids, fecal cholesterol, and fecal bile acids, implying that the hypolipidemic and hypocholesterolemic effects of IFRF were partly attributed to the reduced absorption of lipid and cholesterol. Our results suggested that IFRF could be a potential functional ingredient in the fiber-rich diets for controlling serum cholesterol concentration.     

Cardiovascular protection of deep-seawater drinking water in high-fat/cholesterol fed hamsters

Cardiovascular protection of deep-seawater (DSW) drinking water was assessed using high-fat/cholesterol-fed hamsters in this study. All hamsters were fed a high-fat/cholesterol diet (12% fat/0.2% cholesterol), and drinking solutions were normal distiled water (NDW, hardness: 2.48 ppm), DSW300 (hardness: 324.5 ppm), DSW900 (hardness: 858.5 ppm), and DSW1500 (hardness: 1569.0 ppm), respectively. After a 6-week feeding period, body weight, heart rates, and blood pressures of hamsters were not influenced by DSW drinking waters. Serum total cholesterol (TC), triacylglycerol (TAG), atherogenic index, and malondialdehyde (MDA) levels were decreased (p < 0.05) in the DSW-drinking-water groups, as compared to those in the NDW group. Additionally, increased (p < 0.05) serum Trolox equivalent antioxidant capacity (TEAC), and faecal TC, TAG, and bile acid outputs were measured in the DSW-drinking-water groups. Hepatic low-density-lipoprotein receptor (LDL receptor) and cholesterol-7α-hydroxylase (CYP7A1) gene expressions were upregulated (p < 0.05) by DSW drinking waters. These results demonstrate that DSW drinking water benefits the attenuation of high-fat/cholesterol-diet-induced cardiovascular disorders in hamsters.     

Cholesterol-lowering effect of phytosterol-containing lactic-fermented milk powder in hamsters

Male hamsters were fed six different diets for 4 weeks. Group 1, fed with control diet of regular rodent chow. Group 2, fed with high-fat-high-cholesterol diet containing cholesterol and corn/coconut oil mixture. Group 3, the positive control fed with high-fat-high-cholesterol diet containing 0.74% (w/w) phytosterols. Groups 4–6 were the high-fat-high-cholesterol diet mixed with phytosterol-containing lactic-fermented milk powder (PSFMP) which contains 0.37%, 0.74% and 1.85% (w/w) of phytosterols, respectively. Results demonstrated that PSFMP could significantly decrease (P < 0.05–P < 0.001) the levels of total cholesterol (serum cholesterol), serum triacylglycerol, liver lipids and atherogenic index (LDL-C/HDL-C), while it could also significantly (P < 0.001) increase the level of fecal cholesterol. The pronounced hypolipidemic effects of PSFMP might be attributed to its ability to enhance cholesterol excretion. These results suggest that PSFMP could be used as a potential cholesterol-lowering ingredient in the management of hypercholesterolemia.     

Dietary calcium decreases plasma cholesterol by down‐regulation of intestinal Niemann–Pick C1 like 1 and microsomal triacylglycerol transport protein and up‐regulation of CYP7A1 and ABCG 5/8 in hamsters

Scope: It has been shown that calcium supplementation favorably modifies plasma lipoprotein profile in postmenopausal women. The present study investigated the interaction of dietary calcium with genes of transporters, receptors and enzymes involved in cholesterol metabolism. Methods and results: Forty‐eight ovariectomized hamsters were fed one of the four diets containing 0, 2, 6 and 8 g calcium per kg. Plasma total cholesterol (TC), triacylglycerols (TG), and non‐high density lipoprotein cholesterol were dose‐dependently decreased, whereas high‐density lipoprotein cholesterol (HDL‐C) was dose‐dependently increased with the increasing dietary calcium levels. Dietary calcium had no effect on protein mass of hepatic sterol regulatory element binding protein‐2 (SREBP), liver X receptor‐alpha (LXR), 3‐hydroxy‐3‐methylglutaryl‐CoA reductase (HMGR), LDL receptor (LDLR) and cholesterol‐7α‐hydroxylase (CYP7A1). However, dietary calcium up‐regulated the mRNA levels of hepatic CYP7A1 and intestinal ATP binding cassette transporters (ABCG5/8) whereas it down‐regulated the intestinal Niemann‐Pick C1 like 1 (NPC1L1) and microsomal triacylglycerol transport protein (MTP). In addition, dietary calcium increased the activity of intestinal acyl coenzyme A: cholesterol acyltransferase 2, while it decreased plasma cholesteryl ester transport protein (CETP). Conclusion: Beneficial modification of lipoprotein profile by dietary calcium was mediated by sequestering bile acid absorption and enhancing excretion of fecal cholesterol, via up‐regulation of mRNA CYP7A1 and intestinal ABCG 5/8 with down‐regulation of mRNA NPC1L1 and MTP.     

The role of dietary oxidized cholesterol and oxidized fatty acids in the development of atherosclerosis

The etiology of atherosclerosis is complex and multifactorial but there is extensive evidence indicating that oxidized lipoproteins may play a key role. At present, the site and mechanism by which lipoproteins are oxidized are not resolved, and it is not clear if oxidized lipoproteins form locally in the artery wall and/or are sequestered in atherosclerotic lesions following the uptake of circulating oxidized lipoproteins. We have been focusing our studies on demonstrating that such potentially atherogenic oxidized lipoproteins in the circulation are at least partially derived from oxidized lipids in the diet. Thus, the purpose of our work has been to determine in humans whether oxidized dietary oxidized fats such as oxidized fatty acids and oxidized cholesterol are absorbed and contribute to the pool of oxidized lipids in circulating lipoproteins. When a meal containing oxidized linoleic acid was fed to normal subjects, oxidized fatty acids were found only in the postprandial chylomicron/chylomicron remnants (CM/RM) which were cleared from circulation within 8 h. No oxidized fatty acids were detected in low density lipoprotein (LDL) or high density lipoprotein (HDL) fractions at any time. However, when alpha-epoxy cholesterol was fed to human subjects, alpha-epoxy cholesterol in serum was found in CM/RM and also in endogenous very low density lipoprotein, LDL, and HDL and remained in the circulation for 72 h. In vitro incubation of the CM/RM fraction containing alpha-epoxy cholesterol with human LDL and HDL that did not contain alpha-epoxy cholesterol resulted in a rapid transfer of oxidized cholesterol from CM/RM to both LDL and HDL. We have suggested that cholesteryl ester transfer protein is mediating the transfer. Thus, alpha-epoxy cholesterol in the diet is incorporated into CM/RM fraction and then transferred to LDL and HDL contributing to lipoprotein oxidation. We hypothesize that diet-derived oxidized fatty acids in chylomicron remnants and oxidized cholesterol in remnants and LDL accelerate atherosclerosis by increasing oxidized lipid levels in circulating LDL and chylomicron remnants. This hypothesis is supported by our feeding experiments in animals. When rabbits were fed oxidized fatty acids or oxidized cholesterol, the fatty streak lesions in the aorta were increased by 100%. Moreover, dietary oxidized cholesterol significantly increased aortic lesions in apo-E and LDL receptor-deficient mice. A typical Western diet is rich in oxidized fats and therefore could contribute to the increased arterial atherosclerosis in our population.