Biomedical subjects

Sebely Pal

Publications and source records attributed to Sebely Pal.

At least 19 recordsLinked to original sources

PubMed2006

Atopy, eczema and breast milk fatty acids in a high-risk cohort of children followed from birth to 5 yr.

BACKGROUND: The incidence of atopic diseases such as eczema is increasing in westernized societies. The suggestion that there is a "protective" association between the unique fatty acid composition of breast milk, particularly the omega-3 (n-3) and omega-6 (n-6) essential polyunsaturated fatty acid content, and the development of atopic disease in children was investigated in a cohort study of 263 infants born into families with a history of allergy (one or both parents had asthma, hayfever, eczema). The objectives of this study were to determine the lipid profile [specifically in relation to long-chain polyunsaturated fatty acid (LC-PUFA) composition] in maternal breast milk samples collected at 6 wk and at 6 months following birth, and to investigate the potential role of these fatty acids in modulating the phenotype of children at high genetic risk of developing atopic disease. METHOD: Breast milk samples were available from 91 atopic mothers at their child's ages of 6 wk and 6 months. These samples were analysed for the fatty acid spectrum. Analysis of variance was used to detect differences between groups of outcomes (no atopy or eczema, non-atopic eczema, atopy, atopic eczema) at ages 6 months and 5 yr, and a multiple comparisons procedure was conducted to isolate the parameters producing the different results (F-test, LSD test). For the exposure variables, n-3 and n-6 fatty acids are expressed as weight percentage and as a ratio (at both time-points). RESULTS: The fatty acid profiles of maternal breast milk at 6 wk and 6 months were similar. An increased ratio of n-6: n-3 fatty acids in both 6 wk and 6 month milk samples was associated with non-atopic eczema (p < 0.005) but not atopy alone or atopic eczema. CONCLUSION: We found milk fatty acids were a significant modulator of non-atopic eczema but not atopy or atopic eczema in infants at 6 months. In mothers with a history of asthma, hayfever or eczema, their 6-month-old infants were more likely to develop non-atopic eczema if their milk had a higher ratio of n-6: n-3 LC-PUFA.

Child, Preschool↗

PubMed2006

Individualising weight loss prescription--a management tool for clinicians.

BACKGROUND: Obesity is a global epidemic and a growing cause of comorbidities seen by clinicians. Yet apart from recent guidelines developed by the National Health and Medical Research Council there are few clinical tools available to tackle this problem. OBJECTIVE: This article describes a tool for detecting aspects of both diet and lifestyle likely to adversely affect the body weight of an individual. DISCUSSION: The Diet, Activity and Behaviour Questionnaire (DAB-Q) is designed to identify the nutrition, physical activity and eating behaviours likely to lead to energy imbalance and increased body weight in an individual. This tool can be used in clinical practice to help individualise appropriate behavioural prescriptions for successful weight management.

Australia↗

PubMed2005

The effect of chronic consumption of red wine on cardiovascular disease risk factors in postmenopausal women.

BACKGROUND: Moderate red wine has been shown to reduce cardiovascular disease (CVD) risk, however the effects on certain CVD risk factors are unclear. In this study we have investigated the effects of dealcoholised red wine (DRW) and full-complement red wine (RW) on several cardiovascular risk factors in mildly hypercholesterolaemic postmenopausal women. OBJECTIVES: To elucidate whether the chronic consumption of red wine polyphenols improves risk factors associated with CVD in hypercholesterolaemic postmenopausal women. DESIGN: Forty-five hypercholesterolaemic postmenopausal women were randomly assigned to consume 400 mL/day of either water, DRW or RW for 6 weeks following a 4-week washout. Fasting measures of lipids, lipoproteins, insulin and glucose were taken at 0 and 6 weeks. RESULTS: DRW consumption had no effect of fasting concentrations of lipids, lipoproteins, insulin and glucose. However, chronic consumption of RW significantly reduced fasting LDL cholesterol concentrations by 8% and increased HDL cholesterol concentrations by 17% in hypercholesterolaemic postmenopausal women. CONCLUSIONS: Collectively, regular consumption of full-complement red wine reduces CVD risk by improving fasting lipid levels in hypercholesterolaemic postmenopausal women. This study uniquely demonstrated the LDL cholesterol-lowering effects of red wine in individuals at high CVD risk, which has not previously been shown.

Aged↗

PubMed2005

Red wine polyphenolics suppress the secretion of ApoB48 from human intestinal CaCo-2 cells.

Epidemiological studies suggest that the consumption of red wine lowers the risk of cardiovascular disease. Although the cardioprotective effect of red wine has been attributed to its polyphenolic content, presently, very little is known about the mechanisms by which these compounds benefit the cardiovascular system. Therefore, the aim of this study was to elucidate whether red wine polyphenolics attenuate the synthesis and secretion of proatherogenic chylomicrons from intestinal cells. Apolipoprotein B48 levels (marker of intestinal chylomicrons), quantitated by western blotting, were significantly reduced by 30% in cultured CaCo-2 cells and medium when cells were incubated with either dealcoholized red wine, alcoholized red wine, or atorvastatin compared with controls. Intracellular cholesterol availability was also attenuated in cells incubated with dealcoholized red wine (72.5%), alcoholized red wine (81.5%), and atorvastatin (83.5%) compared to control cells. Collectively, this study suggests that red wine polyphenolics downregulate the production of atherogenic chylomicrons from intestinal cells, which may explain the reduced CVD mortality rates following its consumption.

Anticholesteremic Agents↗

PubMed2005

Margarine phytosterols decrease the secretion of atherogenic lipoproteins from HepG2 liver and Caco2 intestinal cells.

Several studies in humans have demonstrated the hypocholesterolemic effect of plant sterol consumption. It is unclear whether plant sterols regulate lipoprotein metabolism in the liver and intestines, thereby decreasing the levels of circulating atherogenic lipoproteins. We investigated the effect of the three main phytosterols: stigmasterol, campesterol, and beta-sitosterol on lipoprotein production in HepG2 human liver cells and Caco2 human intestinal cells and the mechanisms involved. Cells were incubated for 24h with 50 micromol/L of the different phytosterols or 10 micromol/L of atorvastatin. Very low-density lipoprotein levels (measured by apolipoprotein (apo) B100) in HepG2 cells and chylomicron levels (measured by apoB48) in Caco2 cells were measured using western blotting. Intracellular cholesterol levels were measured using gas chromatography. Analysis was carried out using Student's t-test and ANOVA. Secretion levels of apoB100 significantly decreased by approximately 30% after incubation with all phytosterols compared to control. In addition, cholesterol ester (CE) concentrations significantly decreased when HepG2 cells were incubated with the phytosterols compared to control cells. Secretion of apoB48 from intestinal cells significantly decreased by 15% with stigmasterol, 16% with campesterol and 19% beta-sitosterol compared to control. Collectively the data suggests that plant sterols limit lipid (CE) availability in cells. Decreases in circulating levels of LDL and chylomicron remnants seen in humans with the consumption of margarine phytosterols are possibly due to their effect on lipid production in cells and would therefore reduce the risk of developing cardiovascular disease.

Anticholesteremic Agents↗

PubMed2005

Conjugated linoleic acid suppresses the secretion of atherogenic lipoproteins from human HepG2 liver cells.

Studies in healthy humans have shown that consumption of conjugated linoleic acid (CLA) significantly reduced very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) blood concentrations. We propose that decreased concentrations are due to the inhibition of VLDL production and secretion [measured by apolipoprotein B100 (apoB100)] from the liver. To investigate the effects of a mixture of CLA isomers on VLDL metabolism, HepG2 liver cells were incubated for 24 h with 50 micromol/L of the different fatty acids. Effects of CLA were compared to a saturated fatty acid (palmitic acid), an n-6 fatty acid (linoleic acid) and no treatment (control). HepG2-cell apoB100 levels were measured using Western blotting. ApoB100 secretion was significantly decreased in cells treated with CLA (44%, p<0.005) compared to control cells and those enriched with palmitic acid. Treatment of cells with CLA also decreased intracellular cholesterol levels. Collectively, these results demonstrate that CLA reduces apoB100 production and secretion compared to saturated and polyunsaturated fatty acids, possibly by limiting the availability of free cholesterol (required for apoB100 production). A reduction in apoB100 production in the body would decrease the levels of VLDL and atherogenic LDL and thus reduce the risk of developing cardiovascular disease.

Apolipoprotein B-100↗

PubMed2004

Antimutagenicity of Japanese traditional herbs, gennoshoko, yomogi, senburi and iwa-tobacco.

The multistage induction theory is generally regarded as the mechanism of carcinogenesis. In order to prevent the initiation stage of carcinogenesis, it is meaningful to discover the functional components of edible plants. The objective of this research was to test the antimutagenicity of the functional components of several typical traditional herbs used in Japan. The traditional herbs, gennoshoko (Geranium nepalense var. thunbergii), yomogi (Artemisia vulgaris var. indica), senburi (Swertia japonica), iwa-tobacco (Conandron ramondioides), sarunokoshikake (Elfvingia applanata), kanzo (Glycyeehiza uralensis Fisch) and matatabi (Actinidia polygama) were examined by Ames mutagenesis assay test with Salmonella typhimurium TA98 and TA100 against mutagens, Trp-P-1, Trp-P-2 and B(a)P. The water-soluble components or volatile oil of the herbs were extracted in boiling water. The extracts of gennoshoko showed strong antimutagenicity against B(a)P with S. typhimurium TA98 and TA100, as well as Trp-P-1 and Trp-P-2 with S. typhimurium TA98. Yomogi, senburi and iwa-tobacco were also proved to have good antimutagenicity against Trp-P-1 and Trp-P-2 with S. typhimurium TA98, but weaker antimutagenicity against B(a)P. Other herbs did not show any obvious antimutagenicity against these mutagens. In addition, the volatile oil of yomogi also had remarkable antimutagenic effect against the mutagens we used with S. typhimurium TA98.

Antimutagenic Agents↗

PubMed2004

Red wine polyphenolics suppress the secretion and the synthesis of Apo B48 from human intestinal CaCo-2 cells.

Epidemiological studies suggest that the red wine consumption may reduce the risk factor of cardiovascular disease. However, the mechanisms of how the red wine phenolic components reduce the risk of cardiovascular disease is currently unknown. Our previous study demonstrated that red wine polyphenolics suppress the secretion of pro-atherogenic lipoproteins (very low density lipoproteins) from human hepatic HepG2 cells. Therefore, in this study we hypothesize that red wine polyphenolics will also attenuate the production and secretion of another pro-atherogenic lipoprotein (chylomicrons) from human intestinal CaCo-2 cells. Cultured CaCo-2 cells were incubated in the presence of dealcoholized red wine, alcoholized red wine and atorvastatin for 24 h. The apo B48 protein (marker of intestinal chylomicrons) was quantified on Western blotting and the enhanced chemiluminescence. Apo B48 levels in the cells and that secreted into the media were significantly reduced by 29% in the cells incubated with dealcoholized red wine compared with control cells. Also the similar effect was shown in the cells incubated with alcoholized red wine. The cells incubated with atorvastatin shown the significant reduction of apo B48 production compared to control cells. Collectively, this study suggests that red wine polyphenolics down regulate the production of chylomicron in intestinal CaCo-2 cells.

Apolipoprotein B-48↗

PubMed2004

The effect of acute red wine polyphenol consumption on postprandial lipaemia in postmenopausal women.

Postprandial lipoproteins are potentially atherogenic. The aim of this study was to elucidate whether acute consumption of red wine (RW) and dealcoholised red wine (DRW) regulates postprandial lipid and lipoprotein metabolism in 17 dyslipidaemic postmenopausal women. A mixed meal accompanied by either water, RW or DRW was consumed on three separate visits, in random order, 2 weeks apart. One fasting and 6 hourly postprandial blood samples were taken for lipid analysis. Results showed no significant quantitative changes in postprandial apolipoprotein (apo) B48 levels following the consumption of DRW or RW compared to water. However, qualitatively, DRW may reduce arterial exposure to apoB48-containing lipoproteins over the 6-h postprandial period measured. DRW consumption did not significantly change postprandial TG or insulin levels. A 35% (p = 0.02) increase in postprandial triglyceride (TG) levels and a 54% (p = 0.02) increase in insulin levels were observed following RW consumption, compared to water. In conclusion, acute DRW consumption had no effect on postprandial lipid and lipoprotein metabolism in dyslipidaemic postmenopausal women. However, the consumption of full-compliment RW exacerbated the postprandial lipaemic and insulin response over the 6-h period. Collectively, our findings suggest that neither polyphenols nor red wine reduce atherosclerotic risk by acutely modulating postprandial lipaemia over a 6-h period.

Arteriosclerosis↗

PubMed2003

Alpha-tocopherol modulates the low density lipoprotein receptor of human HepG2 cells.

The aim of this study was to determine the effects of vitamin E (alpha-tocopherol) on the low density lipoprotein (LDL) receptor, a cell surface protein which plays an important role in controlling blood cholesterol. Human HepG2 hepatoma cells were incubated for 24 hours with increasing amounts of alpha, delta, or gamma-tocopherol. The LDL receptor binding activity, protein and mRNA, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase mRNA, cell cholesterol and cell lathosterol were measured. The effect of alpha-tocopherol was biphasic. Up to a concentration of 50 microM, alpha-tocopherol progressively increased LDL receptor binding activity, protein and mRNA to maximum levels 2, 4 and 6-fold higher than control, respectively. The HMG-CoA reductase mRNA and the cell lathosterol concentration, indices of cholesterol synthesis, were also increased by 40% over control by treatment with 50 microM alpha-tocopherol. The cell cholesterol concentration was decreased by 20% compared to control at 50 microM alpha-tocopherol. However, at alpha-tocopherol concentrations higher than 50 microM, the LDL receptor binding activity, protein and mRNA, the HMG-CoA reductase mRNA and the cell lathosterol and cholesterol concentrations all returned to control levels. The biphasic effect on the LDL receptor was specific for alpha-tocopherol in that delta and gamma-tocopherol suppressed LDL receptor binding activity, protein and mRNA at all concentrations tested despite the cells incorporating similar amounts of the three homologues. In conclusion, alpha-tocopherol, exhibits a specific, concentration-dependent and biphasic "up then down" effect on the LDL receptor of HepG2 cells which appears to be at the level of gene transcription. Cholesterol synthesis appears to be similarly affected and the cell cholesterol concentration may mediate these effects.

Journal Article↗

PubMed2003

Effect of atorvastatin on apolipoprotein B48 metabolism and low-density lipoprotein receptor activity in normolipidemic patients with coronary artery disease.

We aimed to examine postprandial dyslipidemia in normolipidemic patients with coronary artery disease (CAD) and the effects of treatment with an hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor (atorvastatin). Subjects with angiographicaly established CAD were randomized to treatment for 12 weeks with 80 mg/d atorvastatin or placebo and the effects on markers of postprandial lipoproteins and low-density lipoprotein (LDL)-receptor binding determined. LDL-receptor binding was determined in mononuclear cells, as a surrogate for hepatic activity. Fasting levels of cholesterol (P <.001), LDL-cholesterol (P <.001), apolipoprotein (apo)B(48) (P =.019), remnant-like particle-cholesterol (RLP-C) (P =.032), and total postprandial apoB(48) area under the curve (AUC) (P =.013) significantly decreased with atorvastatin compared with placebo. Atorvastatin also significantly increased LDL-receptor binding activity (P <.001), and this was correlated with changes in fasting apoB(48) (r =.80, P =.01). We report that aberrations in chylomicron metabolism in normolipidemic CAD subjects are correctable with atorvastatin by a mechanism involving increased LDL-receptor activity. This effect may, in part, explain the cardiovascular benefit of statins used in clinical trials of CAD patients with normal lipid levels.

Adult↗

PubMed2003

Effect of weight loss on postprandial lipemia and low-density lipoprotein receptor binding in overweight men.

Obestity is associated with a range of metabolic abnormalities including fasting and postprandial dyslipidemia, both of which may contribute to increased atherosclerotic risk. Male obese subjects have a decreased level of low-density lipoprotein (LDL) receptor binding in mononuclear cells, the level of which reflects binding in the liver, compared with lean controls. In this study, we investigated whether the implementation of a weight loss regimen in viscerally obese subjects improves LDL receptor binding level. We examined apolipoprotein B(48) (apo B(48)) and retinyl palmitate (RP) metabolism following an oral fat challenge to determine whether weight loss improves postprandial dyslipidemia in viscerally obese subjects. Male obese, mildly dyslipidemic, and insulin-resistant subjects were randomly assigned to either a weight loss (n = 12) or control weight maintenance (n = 10) group. In response to weight loss of 10 kg, insulin sensitivity improved as evidenced by decreased fasting insulin and homeostatic model assessment (HOMA) score. In addition, LDL receptor binding in mononuclear cells increased significantly by 27.5% and LDL-cholesterol was significantly reduced. However, despite the increased LDL receptor levels, fasting apo B(48) levels did not fall. Postprandially, the area under the curve (AUC) for RP was significantly reduced after weight loss, but the incremental and total AUCs for apo B(48) were not altered. Apo B(48) is an unequivocal marker of chylomicron particle number; hence, the reduction in RP metabolism achieved with weight reduction may reflect decreased lipid incorporation into nascent chylomicrons or improved hydrolysis of triglyceride-rich chylomicrons resulting from a decreased competition with hepatic lipoproteins for lipoprotein lipase. Our findings suggest that the improvement in LDL receptor binding following weight reduction of 10 kg in insulin-resistant male obese subjects is insufficient to reduce the elevated chylomicron remnant levels.

Anthropometry↗

PubMed2003

Red wine polyphenolics increase LDL receptor expression and activity and suppress the secretion of ApoB100 from human HepG2 cells.

Epidemiologic studies suggest that the consumption of red wine may lower the risk of cardiovascular disease. The cardioprotective effect of red wine has been attributed to the polyphenols present in red wine, particularly resveratrol (a stilbene, with estrogen-like activity), and the flavonoids, catechin, epicatechin, quercetin and phenolic acids such as gallic acid. At present, very little is known about the mechanisms by which red wine phenolic compounds benefit the cardiovascular system. Therefore, the aim of this study was to elucidate whether red wine polyphenolics reduce lipoprotein production and clearance by the liver. Cultured HepG2 cells were incubated in the presence of dealcoholized red wine, alcohol-containing red wine and atorvastatin for 24 h. The apolipoprotien B100 (apoB100) protein (marker of hepatic lipoproteins) was quantified on Western blots with an anti-apoB100 antibody and the enhanced chemiluminescence detection system. Apolipoprotein B100 levels in the cells and that secreted into the media were significantly reduced by 50% in liver cells incubated with alcohol-stripped red wine compared with control cells. This effect of dealcoholized red wine on apoB100 production in HepG2 cells was similar to the effect of atorvastatin. Apo B100 production was significantly attenuated by 30% in cells incubated with alcoholized red wine, suggesting that the alcohol was masking the effect of red wine polyphenolics. Apo B100 production was significantly attenuated by 45% with the polyphenolic compounds resveratrol and quercertin. In addition, dealcoholized and alcoholized red wine and atorvastatin significantly increased 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase mRNA and LDL receptor binding activity relative to controls. Dealcoholized red wine also increased LDL receptor gene expression. Collectively, this study suggests that red wine polyphenolics regulate major pathways involved in lipoprotein metabolism.

Apolipoprotein B-100↗

PubMed2003

Identification of lipoproteins of intestinal origin in human atherosclerotic plaque.

Apolipoproteins (apo) B48 and B100 are exclusive markers of lipoproteins derived from the intestine and liver, respectively. Lipoproteins of hepatic origin are causally related to atherosclerosis and are found in plaque. However, lipoproteins of intestinal origin have not previously been reported in human atherosclerotic tissue, although studies in animal models suggest that chylomicrons may contribute to arterial cholesterol entrapment. In this study, we report on the relative distribution of both apoB48 and apoB100 in human atherosclerotic tissue. Lipoproteins were isolated from human femoral and carotid endarterectomy samples, from varicose vein and aortic aneurysms. ApoB was determined by Western blot analysis and quantified based on the signal to apoB48 and apoB100 protein standards of known mass. ApoB48 and apoB100 were found in human carotid and femoral endarterectomy samples, but not in varicose vein or aortic aneurysm tissue. The level of apoB48 relative to hepatic lipoproteins (B100) was found to be much greater than would be predicted based on the relative plasma concentration and arterial exposure of the two lipoprotein groups. Intimal association was substantially greater in carotid endarterectomy samples compared to femoral, however, the ratio of chylomicrons to hepatic lipoproteins was greater in the latter. On the basis that chylomicron apoB48 was found in human atherosclerotic tissue and that each chylomicron particle contains substantial quantities of cholesterol, it is possible that the contribution of intestinal lipoproteins to atherosclerosis may be significant.

Aged↗

PubMed2003

The incorporation and metabolism of amyloid-beta into chylomicron-like lipid emulsions.

The aggregation and deposition of amyloid-beta (Abeta) in the brain is thought to be an early event in the pathology of Alzheimer's disease (AD). Many studies have reported the association of Abeta with lipoproteins from plasma suggesting an involvement of lipoprotein particles in Abeta transport. Chylomicron-like lipid emulsions, resembling chylomicrons in composition, size and metabolism were prepared in the presence of [125I]Abeta1-40. Abeta was found to associate significantly with these lipid emulsions during their preparation. The chylomicron-like emulsions containing Abeta were then injected into a lateral ear vein of conscious rabbits and blood sampled at regular intervals up to 30 mins. It was observed that there was no difference in the plasma clearance of [125I]Abeta and that of the 3H-cholesteryl ester, a marker of the emulsion particles, demonstrating that Abeta remains associated with these particles throughout both their lipolysis and tissue uptake. Our results show that Abeta can be metabolised in association with triglyceride rich lipoproteins (TRLs). In addition we report the presence of specific markers of TRLs of hepatic and intestinal origin in human CSF thus suggesting a potential means of cerebral Abeta delivery.

Amyloid beta-Peptides↗

PubMed2002

The effect of Puerariae radix on lipoprotein metabolism in liver and intestinal cells.

BACKGROUND: Animal studies investigating the beneficial effects of Puerariae radix on cardiovascular disease have suggested this plant possesses anti-diabetic and lipid lowering properties. However, the exact mechanism by which Puerariae radix affects lipid metabolism is currently unknown. The aim of this study was to investigate the effect of the water extract of Puerariae radix on the secretion of VLDL and chylomicrons from HepG2 liver cells and CaCo2 cells, respectively, in humans. METHODS: The amount of apoB100 (a protein marker for VLDL) and apoB48 (a protein marker for chylomicrons) in cells and media were quantified by Western Blotting and enhanced chemiluminescence (ECL). Total, free and esterified cholesterol concentrations were measured by gas liquid chromatography. RESULTS: Treatment of cells with water extract of Puerariae radix significantly decreased apoB100 production and secretion from HepG2 cells up to 66% in a dose dependent manner. The intracellular total cholesterol and free cholesterol concentration in HepG2 cells also decreased with increasing concentration of the Puerariae radix. In contrast, water extract of Puerariae radix attenuated apoB48 concentrations in cells, but not apoB48 secretion from CaCo2 enterocytes. CONCLUSIONS: Collectively, our findings suggest that the water extract of Puerariae radix attenuates the hepatic lipoprotein production and secretion. Our present cell culture findings may explain why circulating VLDL and LDL levels were attenuated in animals supplemented with Puerariae radix. Since decreasing the production and secretion of atherogenic lipoproteins decreases the risk of development of cardiovascular disease, diets supplemented with radix may provide a safe and effective beneficial cardioprotective effects in humans.

Apolipoprotein B-100↗

PubMed2002

Cholesterol esters regulate apoB48 secretion in CaCo2 cells.

In this study, we investigated the effect of atorvastatin, an HMG-CoA reductase inhibitor and CL277082, an ACAT inhibitor, on apolipoprotein B48 synthesis, degradation and secretion in transformed human intestinal enterocytes (CaCo2 cells). Cells were incubated with atorvastatin or CL277082 in the absence or presence of sterol containing media and pulsed with [S35]-methionine and chased with unlabelled methionine. Concomitantly, the effect of atorvastatin and CL277082 on the relative amount of apoB48 protein in cells and media was also quantified by western blotting using an apoB antibody and enhanced chemiluminescence. Suppression of cholesterol synthesis with atorvastatin did not attenuate the production or secretion of apoB48 from CaCo2 cells under basal conditions. On the other hand, suppression of cholesterol biosynthesis with atorvastatin under stimulatory conditions accelerated the degradation of apoB48 in cells without affecting its synthesis or secretion. There was no effect of exogenous sterols on apoB48 secretion. Taken together, neither endogenous nor exogenous cholesterol appears to acutely modulate apoB48 secretion from intestinal cells. In contrast, inhibition of cholesterol esterification with ACAT inhibitor significantly attenuated apoB48 secretion under basal and stimulatory conditions by a mechanism which enhanced apoB48 degradation. Collectively, our results suggest that in CaCo2 cells, newly synthesized cholesterol ester may be an immediate regulator apoB48 secretion.

Apolipoprotein B-48↗

PubMed2002

Polyunsaturated fatty acids downregulate the low density lipoprotein receptor of human HepG2 cells.

The aim of the study was to investigate the effect of different fatty acids on the low density lipoprotein (LDL) receptor of cultured human liver HepG2 cells. Previous studies investigating the effect of fatty acids on LDL expression have reported conflicting findings and are limited to measurements of LDL receptor binding activity. Therefore, this study is unique in that the relative effects of different fatty acids on the LDL receptor were investigated at three different stages of expression: 1) functional cellular LDL binding activity, 2) amount of LDL receptor protein and 3) LDL receptor mRNA level. The HepG2 cells were incubated for 24 hr with either 100 &mgr;M palmitic, oleic, linoleic or eicosapentaenoic acid (EPA). The measurement of LDL receptor binding activity was with colloidal gold-LDL conjugates, cellular LDL receptor protein was by western blotting and LDL receptor mRNA by Southern blotting of reverse-transcribed, polymerase chain reaction-amplified cDNA. The LDL receptor binding activity, protein and mRNA levels decreased as the degree of unsaturation of the fatty acids increased (palmitic acid greater-than-or-equal oleic acid > linoleic acid > EPA) and the inverse relationship held whether or not cholesterol was included in the culture media. The relative differences were very similar for the three stages of expression indicating that modulation of the LDL receptor by the fatty acids occurred at the level of gene transcription. The increased susceptibility to oxidation of the polyunsaturated fatty acids was unlikely to be a factor in the effect because EPA and linoleic acid (250 &mgr;M) still downregulated the LDL receptor in the presence of the antioxidant vitamin E (50 &mgr;M). In conclusion, the polyunsaturates, linoleic acid and EPA, effectively downregulated the LDL receptor of HepG2 cells compared to palmitic acid. The effects of these fatty acids were observed at the level of LDL receptor binding activity, protein and mRNA, strongly suggesting that the fatty acid effects were at the level of gene transcription.

Journal Article↗