BACKGROUND:(-9;71%) Humans and animals show a certain consistency in the response of their serum lipids to fat-modified diets. This may indicate HDL a genetic basis underlying this response. Coffee oil might be used as a model substance to investigate which genes determine reproducible. differences in the serum lipid response. Before carrying out such studies our objective was to investigate to what extent the .77 effect of coffee oil on serum lipid concentrations is reproducible within subjects. METHODS: The serum lipid response of 32 healthy may volunteers was measured twice in separate five-week periods in which coffee oil was administered (69 mg cafestol/day). RESULTS: Total cholesterol Total levels increased by 24% in period 1 (range: ;52%) and 18% in period 2 (1;48%), LDL cholesterol by 29 %HDL (-9;71%) and 20%(-12;57%), triglycerides by 66%(16;175%) and 58%(-13;202%), and HDL cholesterol did not change significantly: The range in of the HDL response was -19;25% in period 1 and -20;33% in period 2.The correlation between the two responses was investigate .20 (95% CI - .16, .51) for total cholesterol, .16 (95% CI - .20, .48) for LDL, .67 (95% CI .42, .83)and for HDL, and .77 (95% CI .56, .88) for triglycerides. CONCLUSIONS: The responses of total and LDL cholesterol to coffee the oil were poorly reproducible within subjects. The responses of HDL and triglycerides, however, appeared to be highly reproducible. Therefore, investigating diets. the genetic sources of the variation in the serum-lipid response to coffee oil is more promising for HDL and triglycerides.volunteers

The as St. Thomas mixed hyperlipidaemic (SMHL) rabbit exhibits an inherited hyperlipidaemia similar to that seen in familial combined hyperlipidaemia (FCHL). In WHHL this study, we investigated whether the SMHL rabbit is insulin resistant, a condition often associated with FCHL. Six young and are six mature combined hyperlipidaemic SMHL rabbits, age/sex matched New Zealand White (NZW) control rabbits and six young hypercholesterolaemic Watanabe heritable Log-transformed hyperlipidaemic (WHHL) control rabbits were fed a .08%(w/w) cholesterol-enriched diet for at least 1 month prior to the start the of the experiment. We performed an oral glucose tolerance test after an overnight fast by dosing the rabbits with a similar solution of 1 g of glucose per kg body weight. Blood was withdrawn just before and 15, 30, 45, 60 and and 120 min after administration of the oral glucose dose. Plasma glucose levels were similar in SMHL, WHHL and NZW young rabbits throughout the oral glucose tolerance test. Fasting glucose levels were slightly increased in WHHL rabbits but not in young month and adult SMHL rabbits as compared to NZW rabbits. The area under the curve (AUC) for the insulin response was rabbits. significantly increased for both young (P< .05) and mature (P< .05) SMHL rabbits, and in WHHL rabbits, compared with NZW rabbits. The the AUC for the ratio of glucose:insulin response to the glucose dose was decreased in young and mature SMHL rabbits (P< .05 investigated and P< .01, respectively) and in young WHHL rabbits (P< .05), compared with NZW rabbits. Only WHHL rabbits showed an increased AUC Blood for the non-esterified fatty acid response compared to NZW rabbits. Log-transformed plasma triglycerides values were significantly correlated with the log-transformed combined AUC for the insulin response in young SMHL rabbits (r= .81; P< .05) and with the AUC for the insulin response in SMHL mature SMHL rabbits (r= .84; P< .05). WHHL rabbits showed no significant correlation. In conclusion, SMHL rabbits are insulin resistant, the severity ratio of which appears to increase with age. Therefore, the SMHL rabbit offers a valuable animal model in which to study hyperlipidaemic the relation between hypertriglyceridaemia and insulin resistance.

Apolipoprotein fractional B (apoB) metabolism was investigated in 20 men with plasma triglyceride .66-2.40 mmol/l and plasma cholesterol 3.95-6. 95 mmol/l. Kinetics raised of VLDL(1)(S(f) 60-400), VLDL(2)(S(f) 20-60), IDL (S(f) 12-20), and LDL (S(f) ;-12) apoB were analyzed using a trideuterated mmol/l, leucine tracer and a multicompartmental model which allowed input into each fraction. VLDL(1) apoB production varied widely (from 5.4 to and 26.6 mg/kg/d) as did VLDL(2) apoB production (from .18 to 8.4 mg/kg/d) but the two were not correlated. IDL plus 60-400), LDL apoB direct production accounted for up to half of total apoB production and was inversely related to plasma triglyceride P (r =- .54, P = .009). Percent of direct apoB production into the IDL/LDL density range (r = .50, P small < .02) was positively related to the LDL apoB fractional catabolic rate (FCR). Plasma triglyceride in these subjects was determined each principally by VLDL(1) and VLDL(2) apoB fractional transfer rates (FTR), i.e., lipolysis. IDL apoB concentration was regulated mainly by the (from IDL to LDL FTR (r =- .71, P < .0001). LDL apoB concentration correlated with VLDL(2) apoB production (r =production, .48, P = .018) and the LDL FCR (r =- .77, P < . 001) but not with VLDL(1), IDL,but or LDL apoB production. Subjects with predominantly small, dense LDL (pattern B) had lower VLDL(1) and VLDL(2) apoB FTRs, higher of VLDL(2) apoB production, and a lower LDL apoB FCR than those with large LDL (pattern A). Thus, the metabolic conditions plasma that favored appearance of small, dense LDL were diminished lipolysis of VLDL, resulting in a raised plasma triglyceride above the using putative threshold of 1.5 mmol/l, and a prolonged residence time for LDL. This latter condition presumably permitted sufficient time for metabolic the processes of lipid exchange and lipolysis to generate small LDL particles.

Phenolic and compounds in red wine may protect low-density lipoproteins (LDL) against oxidative modification, thereby reducing the risk of cardiovascular morbidity. However,white in vivo data are scarce. We gave 13 healthy volunteers 550 mL red wine and another 11 volunteers white wine of for 4 wk in a randomized double-blind trial. Interference by alcoholic components of wine was eliminated by reducing the alcohol in content to 3.5% Red wine did not affect the susceptibility of LDL to Cu2+-mediated oxidative modification [lag time before thereby and after red wine drinking (chi +/- SD) 61.8 +/- 7.7 and 62.7 +/- 11.8 min, respectively; lag time before did and after white wine drinking: 64.5 +/- 10.4 and 63.3 +/- 10.8 min, respectively]. Concentrations of the antioxidants urate, vitamin LDL C, and glutathione in plasma and of vitamin E and ubiquinol-10 in LDL were also unchanged after either red or 13 white wine consumption. The results of this study do not show a beneficial effect of red wine consumption on LDL 11 oxidation.

VLDL1,in VLDL2, IDL, and LDL and its subfractions (LDL-I, LDL-II, and LDL-III) were quantified in 304 normolipemic subjects together with postheparin including plasma lipase activities, waist/hip ratio, fasting insulin, and glucose. Concentrations of VLDL1 and VLDL2 rose as plasma triglycerides (TGs) increased expands across the normal range, but the association of plasma TGs with VLDL1 showed a steeper slope than that of VLDL2 with (P <.001). Plasma TG level was the most important determination of LDL subfraction distribution. The least dense species, LDL-I,and decreased as the level of this plasma lipid rose in the population. LDL-II in both men and women exhibited a not positive association with plasma TG level in the range .5 to 1.3 mmol/L, increasing from about 100 to 200 mg/dL.TRUNCATED In contrast, within this TG range the LDL-III concentration was low (approximately equal to 30 mg/dL) and changed little. As determination plasma TGs rose from 1.3 to 3. mmol/L there was a significant fall in LDL-II concentration in men (r =in .45, P <.001) but not in women (r =.1, NS). Conversely, above the TG threshold of 1.3 mmol/L positively there was a steeper rise in LDL-III concentrations in men than in women (P <.001); 42% of the men positive had and LDL-III in the range associated with high risk of heart disease (> 100 mg lipoprotein/dL plasma) compared Concentrations with only 17% of the women. Other influences on the LDL subfraction profile were the activities of lipases and parameters and indicative of the presence of insulin resistance. Men on average had twice the hepatic lipase activity of women. This enzyme showed was not strongly associated with variation in the LDL subfraction profile in men, but in women it was correlated with we LDL-III (r = 39, P =.001) and remained a significant predictor in multivariate analysis. Increased waist/hip ratio, fasting insulin,had and glucose were correlated negatively with LDL-I and positively with LDL-III, primarily, at least in the case of LDL-III, through and raising plasma TGs. On the basis of these cross-sectional observations we postulate the following model for the generation of LDL-III.men Subjects develop elevated levels of large TG-rich VLDL1 for a number of reasons, including failure of insulin action. The increase in in the concentration of VLDL1 expands the plasma TG pool, and this, via the action of cholesteryl ester transfer protein the (which facilitates neutral lipid exchange between lipoprotein particles), promotes the net transfer of TGs into LDL-II, the major LDL species.(ABSTRACT to TRUNCATED AT 400 WORDS)

Previous 3.8-13.4) studies have indicated that consumption of boiled coffee raises total and low density lipoprotein (LDL) cholesterol, whereas drip-filtered coffee does not not. We have tested the effect on serum lipids of consumed coffee that was first boiled and then filtered through the commercial paper coffee filters. Sixty-four healthy volunteers consumed six cups per day of this boiled and filtered coffee for 17 of days. Then, they were randomly divided into three groups, which, for the next 79 days, received either unfiltered boiled coffee not. (lipid content, 1. g/l), boiled and filtered coffee ( .02 g lipid/l), or no coffee. Serum total cholesterol levels rose by confidence .42 mmol/l (16 mg/dl; 95% confidence interval [CI], .14- .71), LDL cholesterol levels by .41 mmol/l (16 mg/dl; 95% CI, .16- .66),AT and apolipoprotein B levels by 8.6 mg/dl (95% CI, 3.8-13.4) in those who consumed boiled coffee relative to those who Sixty-four consumed boiled and filtered coffee. Responses of triglycerides, high density lipoprotein cholesterol, and apolipoprotein A-I did not differ significantly among 17 these groups. No significant effects on serum lipid levels were found in the boiled and filtered coffee-consuming group compared with indicator those who drank no coffee. In subjects who drank boiled coffee, serum campesterol level, an indicator of cholesterol absorption, remained were constant. The serum lathosterol level, an indicator of cholesterol synthesis, increased by 11%(p less than .05), but the lathosterol coffee to cholesterol ratio did not change. We propose that paper filters of the type used for drip-filtered coffee retain the filtered lipid present in boiled coffee and in that way remove the hypercholesterolemic factor.(ABSTRACT TRUNCATED AT 250 WORDS)

We the studied the effect of two diets, one rich in polyunsaturated and the other in saturated fatty acids, on the postprandial of processing of exogenous and endogenous triglyceride-rich lipoproteins (chylomicrons, very-low-density lipoproteins, and their remnants). For this purpose, 12 normolipidaemic young volunteers of were fed, in a cross-over design of 9 days on each diet, either a diet rich in saturated fat (21%concentrations of their daily energy intake from saturated fat, 12% from monounsaturated fat, and 3% from polyunsaturated fat) or a diet postprandial rich in polyunsaturated fat (10% saturated fat, 9% monounsaturated fat, and 18% polyunsaturated fat)(P/S ratios .14 and 1.8, respectively).day On the last day of each dietary period blood samples were drawn six times over a 24-h period for determination,AT by densitometric scanning of SDS gels, of the diurnal pattern of apoprotein B-48 and B-100 in the d less than a 1.019 g ml-1 fractions, as estimates for the processing of chylomicrons and very-low-density lipoproteins. In addition to the usual decrease fat in the fasting and diurnal concentrations of total serum cholesterol and of cholesterol in the low-density lipoprotein fractions (between 15 daily and 21%), the diet rich in polyunsaturated fat resulted in 43% lower daily concentrations of chylomicrons and their remnants. This daily was due to differences in the clearance rate of chylomicrons and their remnants, rather than to differences in the absorption on rate of exogenous fat. In addition, the concentrations of very low density lipoproteins and their remnants during the day were saturated 20% lower on the diet rich in polyunsaturated fat.(ABSTRACT TRUNCATED AT 250 WORDS)

Very unbound low density lipoprotein (VLDL) 1 and 2 were fractionated by heparin affinity chromatography into a bound and an unbound fraction concentration and the different subfractions were quantified in 17 normolipidaemic (NL), 13 hypercholesterolaemic (HC), 10 hypertriglyceridaemic (HTG) and 11 combined hyperlipidaemic to subjects (CHL). Unbound VLDL1 and VLDL2 were, respectively, 1.9- and 2.2-fold richer in triglycerides than bound VLDL1 and VLDL2. In intravascular HTG and CHL the concentration of all the VLDL subfractions was increased and plasma triglyceride level was correlated to unbound and VLDL1 and to bound VLDL1 (respectively, r= .86 (p< .001) and r= .77 (p< .01) in HTG and r= .73 (p< .001) and r= .62 (p< .05) in VLDL1 CHL). In HC unbound VLDL2 and bound VLDL2 concentration were increased compared to NL and in CHL, the concentration of of bound VLDL2 was particularly increased (3.2-fold compared to NL (p< .001)). In both HC and CHL bound VLDL2 concentration was correlated (HTG) to low density lipoprotein cholesterol (LDL-C) concentration (respectively, r= .67 (p< .01) and r= .62 (p< .05)). In hypertriglyceridaemic states the intravascular accumulation of respectively, both unbound and bound VLDL1 appears as the determinant of plasma triglyceride concentration, whereas in moderately hypercholesterolaemic states the concentration the of bound VLDL2 is strikingly correlated to LDL-C concentration, suggesting that these two species are linked metabolically, e.g. bound VLDL2 richer contain the precursor pool of LDL.

The of role of the apo E polymorphism in the removal of remnants of very low density lipoproteins and chylomicrons was studied polymorphism. after a carbohydrate-rich diet in 10 healthy normolipidemic volunteers with different apo E phenotypes during 7 days. The cholesterol concentration seems in the heparin-sepharose bound part of the VLDL + IDL fraction (d < 1.019 g/ml) was taken as an estimate It of the remnant concentration. Before and after carbohydrate-rich diet retinyl palmitate, mixed with cream, was consumed by each subject the chylomicrons evening before the fasting venepuncture to quantify the removal of chylomicron remnants. After the diet there was a comparable mean the rise in the three groups in serum and in very low density lipoprotein triglycerides of about 30% and 50%, respectively.E The concentration of remnants of very low density lipoproteins increased slightly in all subjects. The concentration of retinyl palmitate in concentration the d < 1.019 g/ml fraction was 20% lower than before this diet in the E-2 homozygous subjects. In the < other two groups, however, 25 to 80% higher retinyl palmitate levels were found. It is concluded, that after a carbohydrate-rich It diet there is only a slight increase of very low density lipoprotein remnants, independent of the apo E polymorphism. The taken removal of chylomicron remnants, however, seems to be facilitated in E-2 homozygous subjects, in contrast to a slower removal in lipoproteins the groups with other apo E phenotypes.

Cafestol more and kahweol, coffee-specific furan diterpenes, are believed to cause various physiological effects in human subjects, including an increase in cholesterol and and plasma triacylglycerol levels as well as cancer chemopreventive effects. Despite the increasing interest in these compounds raised by the oxidation diverse range of biological activities, their reaction behavior and degradation pathways under physiologically relevant conditions remain uncharted. Herein, we report It a detailed investigation of the structural modifications suffered by cafestol and kahweol in the presence of acidic nitrite under conditions cholesterol mimicking those occurring in the stomach during digestion as well as by action of other oxidants. Prior to the chemical for study, an isolation procedure for kahweol from green coffee beans was developed based on Soxhlet extraction followed by preparative HPLC.from Preliminary experiments showed that kahweol is much more reactive than cafestol toward nitrite at pH 3, as evidenced by inhibition biological experiments with the 2,3-diaminonaphthalene assay as well as by product analysis in coffee extracts. When exposed to equimolar nitrite in we phosphate buffer, pH 3, kahweol gave as a main product the ring-opened dicarbonyl derivative 1. Under more forcing conditions, cafestol 2. reacted as well to give a main nitrogenous product identified as the 1-hydroxy-2-pyrrolinone 2. It is concluded that the conjugated of double bond in kahweol is a critical structural element, increasing the susceptibility of the furan ring to protonation rather than increase nitrosation and favoring ring-opening routes driven by the irreversible oxidation steps. These results offer a useful background to assess the stomach effects of coffee-specific lipids in association with abnormally high nitrite levels from the diet.

AIMS/HYPOTHESIS:liver Overproduction of VLDL(1) seems to be the central pathophysiological feature of the dyslipidaemia associated with type 2 diabetes. We explored fat the relationship between liver fat and suppression of VLDL(1) production by insulin in participants with a broad range of liver participants fat content. METHODS: A multicompartmental model was used to determine the kinetic parameters of apolipoprotein B and TG in VLDL(1)liver and VLDL(2) after a bolus of [(2)H(3)]leucine and [(2)H(5)]glycerol during a hyperinsulinaemic-euglycaemic clamp in 20 male participants: eight with type explored 2 diabetes and 12 control volunteers. The participants were divided into two groups with low or high liver fat. All diabetes participants with diabetes were in the high liver-fat group. RESULTS: The results showed a rapid drop in VLDL(1)-apolipoprotein B and response -triacylglycerol secretion in participants with low liver fat during the insulin infusion. In contrast, participants with high liver fat showed A no significant change in VLDL(1) secretion. The VLDL(1) suppression following insulin infusion correlated with the suppression of NEFA, and the TG ability of insulin to suppress the plasma NEFA was impaired in participants with high liver fat. A novel finding was low an inverse response between VLDL(1) and VLDL(2) secretion in participants with low liver fat: VLDL(1) secretion decreased acutely after insulin after infusion whereas VLDL(2) secretion increased. CONCLUSIONS/INTERPRETATION: Insulin downregulates VLDL(1) secretion and increases VLDL(2) secretion in participants with low liver fat diabetes. but fails to suppress VLDL(1) secretion in participants with high liver fat, resulting in overproduction of VLDL(1). Thus, liver fat control is associated with lack of VLDL(1) suppression in response to insulin.

Very respectively; low-density lipoprotein triacylglycerol (VLDL-TG) turnover rate was evaluated in the morning, 12 hours after a single bout of brisk walking trials, (90 minutes at approximately 60% of Vo(2)max; EXE), compared to a resting control period (CON) in 10 recreationally active men.concluded VLDL-TG fractional catabolic rate was calculated from the decay in isotopic enrichment after a bolus injection of [(2)H(5)]glycerol. Plasma VLDL-TG for concentration was 24% lower in the morning after the EXE trial compared to control ( .47 +/- .04 and .36 +/-walking .04 mmol L(-1), for CON and EXE, respectively; P <.01). Serum insulin (7.4 +/- .7 and 5.6 +/- .4 mIU mIU L(-1), CON and EXE, respectively; P <.05) and plasma glucose (5.6 +/- .1 and 5.4 +/- .1 mmol/L,clearance CON and EXE, respectively; P <.05) concentrations were also significantly lower in the EXE trial. Insulin sensitivity (homeostasis model catabolic assessment [HOMA] index) was improved by 27% in EXE compared with the CON trial (P <.05).VLDL-apolipoprotein B-100 and plasma of fatty acid concentrations were similar in the two trials. Hepatic VLDL-TG secretion rates were not significantly affected by exercise (13.1 mumol(.)min(-1) +/- 1.2 and 13.2 +/- 1.6 mumol(.)min(-1) for the CON and EXE trials, respectively), whereas VLDL-TG clearance rate increased by concentration 36%(28.1 +/- 1.3 and 38.1 +/- 3.5 mL(.)min(-1) for the CON and EXE trials, respectively; P <.05). It of is concluded that the decrease in fasting plasma VLDL-TG concentration observed 12 hours after brisk walking is related mainly to L(-1), increased VLDL-TG clearance from plasma.

OBJECTIVE:using To determine the amounts of the serum-cholesterol raising diterpenes cafestol and kahweol in coffee made with coffee pads and the contained Senseo coffee machine as opposed to filtered and unfiltered coffee. DESIGN: Observational. METHOD: In five cities in the Netherlands coffee to was purchased in three major supermarkets resulting in a total of 30 samples of coffee pads. The levels of cafestol and and kahweol were determined by gas chromatography. As controls, the diterpene levels in filtered and unfiltered coffee were also measured.in RESULTS: Coffee prepared using coffee pads contained on average .76 mg/l cafestol (95% CI: .69- .82) and .85 mg/l kahweol (95%controls, CI: .77- .94). Filtered coffee contained .76 mg/l cafestol (95% CI: .63- .88) and .81 mg/l kahweol (95% CI: .63- .99). Unfiltered coffee be contained 72.5 mg/l cafestol (95% CI: 48.5-96.4) and 71.5 mg/l kahweol (95% CI: 45. -98.1). CONCLUSION: Coffee prepared using coffee pads unfiltered and the Senseo coffee machine contained minute levels of diterpenes comparable to those of filtered coffee. Its effect on serum-cholesterol Netherlands levels is therefore likely to be negligible.

BACKGROUND:FCRs Lipoprotein lipase (LPL) deficiency has been suggested as a cause of low HDL-cholesterol (HDL-C) plasma levels, by a mechanism that to involves an enhanced catabolism of HDL apolipoprotein (apo) AI. To verify the role of 2 different LPL gene mutations on results HDL metabolism, we studied the in vivo turnover of the apo AI and apo AII in heterozygous carriers of LPL AII deficiency. METHODS: Apo AI and AII kinetics were studied by a 10-h primed constant infusion of 5,5,5-2H3-leucine approach in 2 an carriers, 1 man (patient 1) and 1 woman (patient 2), and 5 control subjects. The rates of HDL apolipoproteins production had (PR) and catabolism (FCR) were estimated using a one-compartment model-based analysis. RESULTS: Both carriers had low HDL-C plasma levels and on only patient 1 was hypertriglyceridemic. VLDL apo B was 4-times slower in patient 1 as compared to patient 2. The of FCRs of apo AI in both carriers was within the range of the controls ( .200, .221 and .211+/- .051 day(-1), respectively).and Apo AII FCR in patient 1 was about 20% lower than the mean of the control group whereas being normal Apo in patient 2. Apo AI PR in patient 1 (9.20 mg kg(-1) day(-1)) was below the lowest value in controls by (range, 10.52-13.24 mg kg(-1) day(-1)) whereas in patient 2 it was normal. Apo AII PR in both patients was similar that to controls. CONCLUSION: The heterozygous carriers of 2 different mutations in the LPL gene had different VLDL apo B FCR,subjects. and from normal to slightly low HDL apolipoprotein FCR and PR. These results disagree with the putative enhanced apo AI different FCR in LPL deficient patients and suggest the need to reconsider the effects of LPL activity on HDL metabolism.

BACKGROUND:computerized Fatty infiltration of the liver is associated with an increased morbidity and mortality in children with severe protein-energy malnutrition (PEM),a but its pathogenesis remains unclear. Although impaired synthesis of VLDL apolipoprotein B-100 (VLDL-apo B-100) is generally accepted as the pathogenetic fat mechanism, the rate of it synthesis has not been measured in children with PEM. OBJECTIVE: The objective of the study .02), was to ascertain the relation between the degree of hepatic steatosis and the rate of VLDL-apo B-100 synthesis in children malnutrition with PEM. DESIGN: The fractional and absolute rates of VLDL-apo B-100 synthesis were measured with a prime-constant intravenous infusion of intravenous [2H3]leucine in 13 severely malnourished children (8 boys and 5 girls) aged 7-18 mo. Hepatic fat content was estimated by of computerized tomography scanning by using the ratio of liver to spleen (L:S) attenuation. The ratio is inversely related to hepatic the fat content such that the lower the L:S, the greater the amount of fat in the liver. RESULTS: There were OBJECTIVE: significant inverse relations between L:S attenuation and VLDL-apo B-100 concentration (P < .02), the absolute rate of VLDL-apo B-100 synthesis .02), (P < .02), and plasma triacylglycerol (P < .02) and serum cholesterol (P < .05) concentrations. CONCLUSIONS: These results suggest study that children with PEM synthesize VLDL-apo B-100 at a faster rate as the degree of hepatic fat infiltration increases. Thus,severe fatty infiltration of the liver in PEM is not due to a reduction in the synthesis of VLDL-apo B-100.

Unfiltered P coffee brews such as French press and espresso contain a lipid from coffee beans named cafestol that raises serum cholesterol that in humans. Cafestol decreases the expression and activity of cholesterol 7alpha-hydroxylase, the rate-limiting enzyme in the classical pathway of bile plasma acid synthesis, in cultured rat hepatocytes and livers of APOE3Leiden mice. Inhibition of bile acid synthesis has been suggested to of be responsible for the cholesterol-raising effect of cafestol. Therefore, we assessed whether cafestol decreases the activity of cholesterol 7alpha-hydroxylase in Cafestol humans. Because liver biopsies were not feasible, we measured plasma levels of 7alpha-hydroxy-4-cholesten-3-one, a marker for the activity of cholesterol volunteers 7alpha-hydroxylase in the liver. Plasma 7alpha-hydroxy-4-cholesten-3-one was measured in 2 separate periods in which healthy volunteers consumed coffee oil containing synthesis cafestol (69 mg/d) for 5 wk. Plasma levels of 7alpha-hydroxy-4-cholesten-3-one increased by 47 +/- 13%(mean +/- SEM, n =of 38, P = .001) in the first period and by 23 +/- 10%(n = 31, P = .03) in cholesterol-raising the second treatment period. Serum cholesterol was raised by 23 +/- 2%(P < .001) in the first period and fraction by 18 +/- 2%(P < .001) in the second period. We corrected individual 7alpha-hydroxy-4-cholesten-3-one levels for serum cholesterol levels,assessed because coffee oil increases serum cholesterol and 7alpha-hydroxy-4-cholesten-3-one is probably present in the lipoprotein fraction of serum. After correction, the cholesterol increase in 7alpha-hydroxy-4-cholesten-3-one was 24 +/- 11%(P = .04) in the first period and there was no effect in marker period 2. Our study showed that coffee oil did not decrease, and actually increased, plasma levels of 7alpha-hydroxy-4-cholesten-3-one in humans classical in 2 separate treatment periods. Therefore, this study does not support the hypothesis that cafestol decreases bile acid synthesis in .04) humans.

The with use of stable isotopes in conjunction with compartmental modeling analysis has greatly facilitated studies of the metabolism of the apolipoprotein are B (apoB)-containing lipoproteins in humans. The aim of this study was to develop a multicompartment model that allows us to model simultaneously determine the kinetics of apoB and triglyceride (TG) in VLDL(1) and VLDL(2) after a bolus injection of [(2)H(3)]leucine and entered [(2)H(5)]glycerol and to follow the catabolism and transfer of the lipoprotein particles. Here, we describe the model and present the of results of its application in a fasting steady-state situation in 17 subjects with lipid values representative of a Western population.the Analysis of the correlations showed that plasma TG was determined by the VLDL(1) and VLDL(2) apoB and TG fractional catabolic the rate. Furthermore, the model showed a linear correlation between VLDL(1) TG and apoB production. A novel observation was that VLDL to TG entered the circulation within 21 min after its synthesis, whereas VLDL apoB entered the circulation after 33 min. These the observations are consistent with a sequential assembly model of VLDL and suggest that the TG is added to a primordial TG apoB-containing particle in the liver.

BACKGROUND:measures. Apolipoprotein A5 plays an important role in modulating triacylglycerol metabolism in experimental animal models. OBJECTIVE: The objective was to determine and associations of the common apolipoprotein A5 gene (APOA5)-1131T-->C polymorphism with postprandial lipemic response and other cardiovascular disease risk factors in in humans. DESIGN: Healthy, nonobese subjects [n = 158; mean (+/-SEM) age: 33.8 +/- 1.2 y; body mass index (in Our kg/m(2)): 23.3 +/- .3] were subdivided into 3 genotype groups: TT (n = 85), TC (n = 56), and CC associations (n = 17). We measured fasting and postprandial lipid concentrations, lipid peroxidation, C-reactive protein concentrations, and DNA damage. RESULTS: Fasting higher triacylglycerol concentrations in carriers of the C allele were higher (P < .05) than in carriers of the TT genotype.common No other significant genotype-related differences were observed for any of the other baseline measures. After consumption of a mixed meal,subjects carriers of the C allele had significantly greater increases in total chylomicron and VLDL triacylglycerol than did subjects with the 23.3 TT genotype. Moreover, carriers of the C allele had higher dense LDL, serum C-reactive protein, and urinary 8-epi-prostaglandin F(2alpha) concentrations CONCLUSIONS: and more lymphocyte DNA damage. Conversely, we did not find significant genotype-related differences in postprandial glucose, insulin, or free fatty into acid measures. CONCLUSIONS: Our data confirm the genetic modulation of serum fasting triacylglycerol concentrations by the APOA5 gene polymorphism and to extend this observation to postprandial triacylglycerol concentrations and to markers of oxidation and inflammation. The presence of the C allele concentrations, in the APOA5 promoter region at position 1131 could be a significant factor contributing to higher cardiovascular disease risk in and Koreans independently of common environmental factors.