Transfer of apolipoproteins between plasma lipoproteins and exogenous lipid particles after repeated bolus injections or during a continuous infusion of fat emulsion

Recent studies on the metabolism of artificial lipid particles in a fat emulsion (exo TG) revealed that exo TG acquired apolipoproteins in vivo and in vitro. In particular, apolipoproteins C-II and C-III (apo C-II and apo C-III) are rapidly transferred from high-density lipoprotein (HDL) to exo TG, and return to HDL after the hydrolysis of exo TG. The present study was undertaken to examine whether the movement of apo C-II and apo C-III between HDL and exo TG is influenced by a prior injection of fat emulsion. Two experiments were undertaken. In experiment 1, six male volunteers received three bolus injections of a fat emulsion at a dose of 0.1 g of TG/kg with intervals of 90 min between injections. In experiment 2, the plasma concentrations of triglycerides were maintained at approximately 500 mg/dl for 160 min by the continuous infusion of exo TG. Levels of apo C-II and apo C-III, and the elimination rate of exo TG were followed in each test. In experiment 1, the movement of apolipoproteins between exo TG and HDL was unchanged between the first, second, and third bolus. The elimination rate of exo TG after the third bolus was higher than that after the first bolus. In experiment 2, after the administration of exo TG, the levels of C apolipoproteins in the fraction of HDL began to decrease, and those in the fraction of very-low-density lipoprotein that contained exo TG began to increase. When the concentrations of triglycerides in plasma reached a plateau, the distribution of C apolipoproteins in the lipoprotein fraction also stabilized.(ABSTRACT TRUNCATED AT 250 WORDS)     

Apolipoprotein C-II modifications associated with an infusion of artificial lipid particles

Artificial lipid particles used as parenteral nutrition solution do not contain any apolipoproteins when they are infused into the circulation. Despite the absence of apolipoproteins, the metabolism of artificial lipid particles is similar to that of chylomicrons which contain various kinds of apolipoprotein. Of the known apolipoproteins, apolipoprotein C-II (apo C-II) is important in the hydrolysis of triglyceride-rich lipoproteins via involvement in the activation of lipoprotein lipase. Modifications of apo C-II associated with intravenous infusion of a lipid emulsion were investigated in eight patients. Changes in apo C-IIs in high density lipoproteins (HDL), low density lipoproteins (LDL) and very low density lipoproteins (VLDL) together with the plasma level of triglycerides, were quantified before and for 90 min after a bolus injection of a 10% lipid emulsion (1 ml/kg of body weight). Immediately prior to the injection, 54% of the total amount of apo C-II was present in HDL, while 27% was present in VLDL. After 5 to 10 min, the amount of apo C-II in HDL decreased to 29% of the total, while that in VLDL increased to 62%. Subsequently, the amounts of apo C-II in HDL and VLDL began to return to the preinjection levels. These variations in apo C-II were closely correlated with the plasma clearance of triglyceride. The result indicates that the injected lipids are not inert particles during their short intravascular life, but that they acquire apo C-II from HDL.     

Capacity of high-density lipoprotein for donating apolipoproteins to fat particles in hypertriglyceridemia induced by fat infusion.

Acquisition of apolipoproteins C-II (apoCII) and C-III (apoCIII) is essential for the regulation of intravascular metabolism of fat particles (exoTG). This study was undertaken to investigate whether the capacity of high-density lipoprotein (HDL) for donating apoCII and apoCIII is influenced by the concentration of triglycerides (TGs) in plasma. A fat emulsion was infused into six male volunteers at a rate of 0.5 g TG.kg-1.h-1 (priming dose) for 30 min. For the following 160 min, fat was infused a fat emulsion was infused into the same subjects at a rate of 0.3 g.kg-1.h-1 for 160 min after the administration of the priming dose of fat emulsion for 30 min (experiment 2). The plasma TG concentrations and the amounts of apoCII and apoCIII in exo TG and HDL were monitored. The concentration of TG in the plasma stabilized at approximately 500 mg/dl in experiment 1, whereas it continued to increase to 815 +/- 42 mg/dl at 160 min after the start of the infusion of the fat emulsion in experiment 2. In experiment 1, the amount of both apoCII and apoCIII began to increase in exoTG and to decrease in HDL after the initiation of fat infusion. These changes in the distribution of apoC stabilized while the TG concentration remained at a plateau value. However, in experiment 2, the amount of apoC in exoTG did not increase further in response to the additional rise in plasma TG level. These results suggest that there is a relative lack of apoC that can be donated by HDL, depending on the quantitative balance between exoTG and HDL.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glucosyl hesperidin lowers serum triglyceride level in hypertriglyceridemic subjects through the improvement of very low-density lipoprotein metabolic abnormality

To examine the serum triglyceride (TG)-lowering effect of a soluble hesperidin derivative, glucosyl hesperidin (G-hesperidin), and its mechanisms, we carried out a G-hesperidin administration test in hypertriglyceridemic subjects. G-Hesperidin was administered to the subjects at 500 mg/d for 24 wk. In this study, the subjects were classified into high-TG type (TG > 150 mg/dL), borderline-TG type (TG 110-150 mg/dL) and normal-TG type (TG < 110 mg/dL) on the basis of their initial serum TG values. Among these phenotypes, serum TG level significantly decreased in the high-TG type during the G-hesperidin administration period. It was also observed that elevated values of serum remnant-like particle cholesterol (RLP-C), apolipoprotein (apo) B, apo C-II, apo C-III and apo E occurred in the high-TG type and that these serum levels were significantly reduced by G-hesperidin administration. Moreover, polyacrylamide gel electrophoresis analysis of serum lipoproteins revealed that the very low-density lipoprotein (VLDL)/low-density lipoprotein (LDL) ratio and LDL migration index of the high-TG type were remarkably higher than those of the other phenotypes but that their high values were significantly reduced by the administration. These results indicate that G-hesperidin preferentially lowers serum TG in hypertriglyceridemic subjects and that this effect is possibly caused by the improvement of VLDL metabolic abnormality, leading to the reduction of small dense LDL.     

Effect of protein, unsaturated fat, and carbohydrate intakes on plasma apolipoprotein B and VLDL and LDL containing apolipoprotein C-III: results from the OmniHeart Trial

BACKGROUND: Plasma apolipoprotein B (apo B) and VLDL and LDL with apolipoprotein C-III (apo C-III) are independent risk factors for cardiovascular disease (CVD). Dietary intake affects lipoprotein concentration and composition related to those apolipoproteins. OBJECTIVE: We studied differences in apo B lipoproteins with and without apo C-III after 3 healthy diets based on the Dietary Approaches to Stop Hypertension Trial diet. DESIGN: Healthy participants (n = 162) were fed each of 3 healthy diets for 6 wk in a crossover design. Diets differed by emphasis of either carbohydrate (Carb), unsaturated fat (Unsat), or protein (Prot). Blood was collected at baseline and after diets for analysis. RESULTS: Compared with the Carb diet, the Prot diet reduced plasma apo B and triglycerides in VLDL with apo C-III (16%, P = 0.07; 11%, P = 0.05, respectively) and apo B in LDL with apo C-III (16%, P = 0.04). Compared with the Unsat diet, the Prot diet reduced triglycerides in VLDL with apo C-III (16%, P = 0.02). Compared with baseline (subjects' usual diet was higher in saturated fat), the Prot diet reduced apo B in LDL with apo C-III (11%, P = 0.05), and all 3 diets reduced plasma total apo B (6-10%, P < 0.05) and apo B in the major type of LDL, LDL without apo C-III (8-10%, P < 0.01). All 3 diets reduced the ratio of apo C-III to apo E in VLDL. CONCLUSIONS: Substituting protein for carbohydrate in the context of a healthy dietary pattern reduced atherogenic apo C-III-containing LDL and its precursor, apo C-III-containing VLDL, resulting in the most favorable profile of apo B lipoproteins. In addition, compared with a typical high-saturated fat diet, healthy diets that emphasize carbohydrate, protein, or unsaturated fat reduce plasma total and LDL apo B and produce a lower more metabolically favorable ratio of apo C-III to apo E.     

Increased plasma concentrations of lipoprotein(a) during a low-fat, high-carbohydrate diet are associated with increased plasma concentrations of apolipoprotein C-III bound to apolipoprotein B-containing lipoproteins

BACKGROUND: Low-fat, high-carbohydrate (LFHC) diets have been shown to increase plasma concentrations of lipoprotein(a) [Lp(a)] and of triacylglycerol- rich lipoproteins (TRLs). OBJECTIVE: We tested whether increases in plasma Lp(a) induced by an LFHC diet are related to changes in TRLs. DESIGN: Healthy men (study 1; n = 140) consumed for 4 wk each a high-fat, low-carbohydrate diet (HFLC; 40% fat, 45% carbohydrate) and an LFHC diet (20% fat, 65% carbohydrate). Plasma lipids; lipoproteins; apolipoprotein (apo) B, A-I, and C-III; and Lp(a) were measured at the end of each diet. In a second group of men following a similar dietary protocol (study 2; n = 33), we isolated apo(a)-containing particles by immunoaffinity chromatography and determined the concentrations of apo C-III in ultracentrifugally isolated subfractions of apo B-containing lipoproteins. RESULTS: In study 1, plasma concentrations of Lp(a) (P < 0.001), triacylglycerol (P < 0.001), apo B (P < 0.005), apo C-III (P < 0.005), and apo C-III in apo B-containing lipoproteins (non-HDL apo C-III) (P < 0.001) were significantly higher with the LFHC diet than with the HFLC diet. Stepwise multiple linear regression analysis showed that the association of changes in Lp(a) with changes in non-HDL apo C-III was independent of changes in body mass index, apo B, LDL cholesterol, and HDL cholesterol. Plasma lipid and lipoprotein changes were similar in study 2, and we found that both total apo C-III and the apo C-III content of apo(a)-containing particles were increased in a TRL fraction consisting predominantly of large VLDL particles [TRL-apo(a)]. CONCLUSIONS: The increase in plasma Lp(a) with an LFHC diet is significantly associated with an increase in non-HDL apo C-III. Enrichment of TRL-apo(a) with apo C-III may contribute to this dietary effect on Lp(a) concentrations.     

Effects of guar gum on plasma lipoproteins and apolipoproteins C-II and C-III in patients affected by familial combined hyperlipoproteinemia

In recent years, guar gum has been shown to be a potent hypocholesterolemic agent. The effects of this fiber on triglycerides are less clear. In order to evaluate the influence of guar supplementation on plasma lipoproteins and apolipoprotein C-II (apoC-II) and apolipoprotein C-III (apoC-III) isoforms (apoC-III2, apoC-III1, apoC-III0), 16 g/day of guar gum were administered to 12 outpatients affected by familial combined hyperlipoproteinemia for a period of 60 days. Mean total cholesterol and triglyceride levels significantly decreased after 15 days of treatment and persisted reduced at the 30th and 60th day of guar supplementation. While low-density lipoprotein cholesterol paralleled the reduction of total plasma cholesterol, we did not observe any change in the cholesterol content of high-density lipoprotein (HDL) subfractions (HDL2 and HDL3) during the study. A redistribution of the relative content of very low-density lipoprotein apoC-III isoforms with a significant increase of apoC-III1 and a decrease of apoC-III0 was observed after 15, 30, and 60 days of guar gum administration. The results show that guar gum reduces not only cholesterol but also triglyceride levels in patients affected by familial combined hyperlipoproteinemia. Further studies are needed to confirm the suggestion that the different distribution of very low-density lipoprotein apoC-III isoforms induced by guar supplementation may influence the behavior of plasma triglycerides.     

Arterial deepvenous difference of lipoproteins in skeletal muscle of patients in postoperative state: effects of medium chain triglyceride emulsion

The effect of fat infusion with medium chain triglycerides (MCT) and long chain triglycerides (LCT) on serum lipoproteins before and after passage through the skeletal muscle was investigated with the forearm technic in eight patients after abdominal operation. All lipoprotein fractions were enriched with triglycerides and phospholipids from infused artificial fat particles with the consequence of significantly increased ratios of TG/PL and TG/apo B in VLDL, of TG/apo B in LDL and TG/apo A-I in HDL. Uptake and release of lipoprotein components by skeletal muscle are given by arterial-deepvenous differences considering the blood flow rates. The positive arterial-deepvenous difference of VLDL triglycerides after 4-hr infusion is interpreted as cleavage and uptake of infused MCT by the muscle. The release of LDL is more pronounced after the fat infusion than before, suggesting a degradation and enhanced catabolism of artificial fat particles. HDL release may be also a consequence of catabolism of artificial TG/PL-particles. These results indicate an uptake of MCT/LCT emulsion by the skeletal muscle.     

Serum apolipoprotein A-I levels: relationship to lipoprotein lipid levels and selected demographic variables

Serum apolipoprotein A-I (apo A-I) and lipoprotein cholesterol and triglycerides were measured in 289 persons randomly selected from a Northern California industrial population in 1974-1976. Apo A-I and high density lipoprotein (HDL) cholesterol were strongly correlates with one another and both were inversely correlated with very low density lipoprotein (VLDL) triglycerides. The decrease in HDL-cholesterol with increasing VLDL-triglycerides was relatively much larger than the concomitant decrease in apo A-I. The relative decrease in the sum of cholesterol and triglycerides in the HDL fraction was similar to that for apo A-I, suggesting that the decreasing HDL-cholesterol:apo A-I ratio with increasing VLDL-triglycerides is due in large part to reciprocal transfer of cholesteryl esters for triglycerides between HDL and VLDL. Mean apo A-I level was 16 mg/dl higher in women not taking exogenous sex steroids than in men, 31 mg/dl higher in women taking estrogens without progestins and 10 mg/dl higher in contraceptive drug users than in other women, and 8 mg/dl higher in black than in white men. The first two of these differences were statistically significant. Apo A-I level was unrelated to age, but increased with ethanol consumption and decreased with adiposity. An inverse relationship between Apo A-I and cigarette smoking was found among women.     

Dietary monounsaturated fat activates metabolic pathways for triglyceride-rich lipoproteins that involve apolipoproteins E and C-III

BACKGROUND: Dietary monounsaturated fat (MUFA) and complex carbohydrates have different effects on triglyceride-rich lipoprotein (TRL) metabolism. OBJECTIVE: We hypothesized that apolipoprotein (apo) E and apo C-III might be involved in these dietary effects because of their crucial role in TRL metabolism. DESIGN: Twelve adults consumed, for 3 wk each, 2 isocaloric diets: first a carbohydrate-rich diet (48% complex carbohydrate, 8% MUFAs) and then a MUFA-rich diet (31% complex carbohydrate, 24% MUFAs) 12 mo later. The dietary composition of other macronutrients in the 2 diets was similar. Body weight was kept constant. Postprandial apo B kinetic studies using stable-isotope tracers were performed after each dietary intervention. Multiple VLDL, intermediate-density lipoprotein (IDL), and LDL fractions were prepared on the basis of apo E and apo C-III contents. RESULTS: The MUFA diet increased by approximately 4-6-fold, the secretion of VLDLs and IDLs containing both apo E and apo C-III (E+CIII+) (P < 0.05). These are TRLs that mostly cleared from the circulation and are minor precursors of LDL. The MUFA diet also decreased by 60% (P < 0.05) the secretion of the TRLs without apo E or apo C-III (major precursors of LDL in plasma) and decreased their flux to LDLs. Total LDL flux did not change because the MUFA diet increased the flux to LDL from E-CIII+ TRLs, a process that requires the removal of apo C-III. In addition, the MUFA diet significantly increased the TRL fractional catabolic rate by 50% and doubled the percentage of TRLs that were cleared rather than being converted to LDLs. CONCLUSION: MUFA intake activates synthetic and rapid catabolic pathways for TRL metabolism that involve apo E and apo C-III and suppresses the metabolism of more slowly metabolized VLDLs and IDLs, which do not contain these apolipoproteins.     

Influence of artificial fat emulsions on the composition of serum lipoproteins in humans

Infusions of about 50 g soya oil, emulsified with egg lecithin (Intralipid) or soya lecithin (Lipofundin) have different effects on the composition of serum lipoprotein fractions in volunteers (n = 6). Triglycerides are altered in all lipoprotein fractions most in lowest density classes but also in LDL and HDL. Differences in maximal concentrations (higher during Intralipid) and differences in removal rate of triglycerides (faster with Lipofundin) are due to different emulsifiers. Cholesterol increase in VLDL and decrease in HDL3 are independent from emulsifier. Intralipid produces an increase of phospholipids in all lipoprotein fractions, Lipofundin only in VLDL. Linoleic acid in lecithin fatty acids of lipoprotein fractions is increased by Lipofundin and decreased by Intralipid. Apolipoprotein A-I and A-II decrease in HDL3 and slightly increase in HDL2. During both infusions apolipoprotein C-II increases significantly after Intralipid.     

Responses of plasma lipoproteins and sex hormones to the consumption of lean fish incorporated in a prudent-type diet in normolipidemic men

OBJECTIVE: The effects of lean fish on plasma lipoproteins, postheparin plasma lipolytic activities and sex hormones were examined in 11 normolipidemic male subjects. METHODS: This study was a randomized crossover trial of two isoenergetic prudent-type diets, lean fish diet and beef, pork, veal, eggs and milk (nonfish) diet. Experimental diets provided approximately 11800 kJ--18% as proteins, 50% as carbohydrates, 32% as lipids [ratio of polyunsaturated to saturated fatty acids (P:S) of 1:1 compared with 0.5:1 in preexperimental diet], and 260 mg cholesterol/day. RESULTS: Compared with the nonfish diet, the lean fish diet induced higher plasma total and LDL apolipoprotein (apo) B and apo B:apo A-1 ratio, indicating that the substitution of lean fish for beef, veal, pork, eggs and milk provides little benefits with regard to plasma apo B concentrations in a low-fat high P:S diet. Moreover, triglycerides:apo B and cholesterol:apo B ratios of VLDL were lower following the lean fish diet than the nonfish diet, suggesting the presence of smaller very low-density lipoprotein (VLDL) particles following the consumption of lean fish. Higher plasma concentrations of sex hormone-binding globulin (SHBG), HDL2 cholesterol and HDL2:HDL3 cholesterol ratio were found with the lean fish diet compared with the nonfish diet. Negative correlations between plasma postheparin lipoprotein lipase (LPL) activity and VLDL triglycerides (n = 11, r = -0.53, p = 0.02), and between plasma postheparin LPL activity and VLDL triglycerides:apo B ratio (n = 11, r = -0.64, p = 0.02) were also observed following the lean fish diet. CONCLUSION: These results suggest that the effects of substituting lean fish for beef, veal, pork, eggs and milk on plasma lipoproteins may be partly associated with variations in plasma sex hormone status and plasma LPL activity in normolipidemic men.     

Magnesium deficiency affects plasma lipoprotein composition in rats

Weanling rats were pair-fed for 8 d with control and Mg-deficient diets containing 960 and 30 mg of Mg/kg, respectively. The marked reduction in plasma Mg levels indicated that the rats fed the Mg-deficient diet were indeed deficient. In the Mg-deficient rats the percent composition of triglycerides in VLDL, LDL and HDL was elevated and that of protein was reduced. Although the proportion of cholesterol was reduced in LDL and HDL, that of phospholipid was decreased only in HDL. Magnesium deficiency induced a decrease in the percent composition of apolipoprotein (apo) E and a relative increase in the apo C for VLDL. In HDL from Mg-deficient rats, the proportion of apo AI was higher than normal, apo AIV was lower than normal and apo E was virtually absent. The percent composition of oleic and linoleic acids was increased but that of stearic and arachidonic acids was depressed in both VLDL and HDL derived from Mg-deficient rats compared with pair-fed controls. Whether these alterations in lipoprotein profile contribute to hyperlipoproteinemia or are the results of the metabolic changes that produce hyperlipoproteinemia remain to be determined.     

Randomized controlled trial of the effect of n-3 fatty acid supplementation on the metabolism of apolipoprotein B-100 and chylomicron remnants in men with visceral obesity

BACKGROUND: Lipid abnormalities may contribute to the increased risk of atherosclerosis and coronary disease in visceral obesity. Fish oils lower plasma triacylglycerols, but the underlying mechanisms are not fully understood. OBJECTIVE: We studied the effect of fish oils on the metabolism of apolipoprotein B-100 (apo B) and chylomicron remnants in obese men. DESIGN: Twenty-four dyslipidemic, viscerally obese men were randomly assigned to receive either fish oil capsules (4 g/d, consisting of 45% eicosapentaenoic acid and 39% docosahexaenoic acid as ethyl esters) or matching placebo (corn oil, 4 g/d) for 6 wk. VLDL, intermediate-density lipoprotein (IDL), and LDL apo B kinetics were assessed by following apo B isotopic enrichment with the use of gas chromatography-mass spectrometry after an intravenous bolus injection of trideuterated leucine. Chylomicron remnant catabolism was measured with the use of an intravenous injection of a chylomicron remnant-like emulsion containing cholesteryl [(13)C]oleate, and isotopic enrichment of (13)CO(2) in breath was measured with isotope ratio mass spectrometry. Kinetic values were derived with multicompartmental models. RESULTS: Fish oil supplementation significantly (P < 0.05) lowered plasma concentrations of triacylglycerols (-18%) and VLDL apo B (-20%) and the hepatic secretion of VLDL apo B (-29%) compared with placebo. The percentage of conversions of VLDL apo B to IDL apo B, VLDL apo B to LDL apo B, and IDL apo B to LDL apo B also increased significantly (P < 0.05): 71%, 93%, and 11%, respectively. Fish oils did not significantly alter the fractional catabolic rates of apo B in VLDL, IDL, or LDL or alter the catabolism of the chylomicron remnant-like emulsion. CONCLUSION: Fish oils effectively lower the plasma concentration of triacylglycerols, chiefly by decreasing VLDL apo B production but not by altering the catabolism of apo B-containing lipoprotein or chylomicron remnants.     

Fish consumption shifts lipoprotein subfractions to a less atherogenic pattern in humans

The effect of fish consumption on plasma lipoprotein subfraction concentrations was studied in 22 men and women (age > 40 y). Subjects were provided an average American diet (AAD, 35% of energy as fat, 14% as saturated fat, and 35 mg cholesterol/MJ) for 6 wk before being assigned to a National Cholesterol Education Program (NCEP) Step 2 high-fish diet (n = 11, 26% of energy as fat, 4.5% as saturated fat, and 15 mg cholesterol/MJ) or a NCEP Step 2 low-fish diet (n = 11, 26% of energy as fat, 4.0% as saturated fat, and 11 mg cholesterol/MJ) for 24 wk. All food and drink were provided to study participants. Consumption of the high-fish NCEP Step 2 diet was associated with a significant reduction in medium and small VLDL, compared with the AAD diet, whereas the low-fish diet did not affect VLDL subfractions. Both diets significantly reduced LDL cholesterol concentrations, without modifying LDL subfractions. Both diets also lowered HDL cholesterol concentrations. However, the high-fish diet significantly lowered only the HDL fraction containing both apolipoprotein (apo) AI and AII (LpAI:AII) and did not change HDL subfractions assessed by NMR, whereas the low-fish diet significantly lowered the HDL fraction containing only apo AI (LpAI) and the large NMR HDL fractions, resulting in a significant reduction in HDL particle size. Neither diet affected VLDL and LDL particle size. Our data indicate that within the context of a diet restricted in fat and cholesterol, a higher fish content favorably affects VLDL and HDL subspecies.     

Rapid induction of essential fatty acid deficiency by intragastric infusion of triolein-supplemented total parenteral nutrition solutions: evidence of increased hepatic cholesterol esterification in the rat

Rats were fed linoleic acid from a safflower oil emulsion or triolein-supplemented total parenteral nutrition solutions by continuous intragastric infusion for 7 and 14 d. Biochemical signs of essential fatty acid deficiency (EFAD) developed in rats supplemented with triolein compared with those receiving linoleic acid, and the relationship between hepatic cholesterol esterification and the distribution of free cholesterol in plasma lipoproteins was investigated in the EFAD and control animals. Results indicate that hepatic triglyceride (TG) and cholesterol ester content are greater and plasma levels of TG and cholesterol are lower in triolein-supplemented groups. Hepatic accumulation of cholesterol esters is associated with an increase in hepatic acyl-CoA:cholesterol acyltransferase activity and also with plasma very low density lipoprotein (VLDL) and high-density lipoprotein (HDL), which contain a greater proportion of cholesterol esters. These data suggest that EFAD can be rapidly induced with continuous intragastric feeding and that hepatic accumulation of cholesterol esters and enrichment of VLDL and HDL with cholesterol esters are early indicators of EFAD in the rat.     

Greater enrichment of triacylglycerol-rich lipoproteins with apolipoproteins E and C-III after meals rich in saturated fatty acids than after meals rich in unsaturated fatty acids

BACKGROUND: Although there is considerable interest in the postprandial events involved in the absorption of dietary fats and the subsequent metabolism of diet-derived triacylglycerol-rich lipoproteins, little is known about the effects of meal fatty acids on the composition of these particles. OBJECTIVE: We examined the effect of meal fatty acids on the lipid and apolipoprotein contents of triacylglycerol-rich lipoproteins. DESIGN: Ten normolipidemic men received in random order a mixed meal containing 50 g of a mixture of palm oil and cocoa butter [rich in saturated fatty acids (SFAs)], safflower oil [n-6 polyunsaturated fatty acids (PUFAs)], or olive oil [monounsaturated fatty acids (MUFAs)] on 3 occasions. Fasting and postprandial apolipoproteins B-48, B-100, E, C-II, and C-III and lipids (triacylglycerol and cholesterol) were measured in plasma fractions with Svedberg flotation rates (S(f)) >400, S(f) 60-400, and S(f) 20-60. RESULTS: Calculation of the composition of the triacylglycerol-rich lipoproteins (expressed per mole of apolipoprotein B) showed notable differences in the lipid and apolipoprotein contents of the SFA-enriched particles in the S(f) > 400 and S(f) 60-400 fractions. After the SFA meal, triacylglycerol-rich lipoproteins in these fractions showed significantly greater amounts of triacylglycerol and of apolipoproteins C-II (S(f) 60-400 fraction only), C-III, and E than were found after the MUFA meal (P < 0.02) and more cholesterol, apolipoprotein C-III (S(f) > 400 fraction only), and apolipoprotein E than after the PUFA meal (P < 0.02). CONCLUSIONS: Differences in the composition of S(f) > 400 and S(f) 60-400 triacylglycerol-rich lipoproteins formed after saturated compared with unsaturated fatty acid-rich meals may explain differences in the metabolic handling of dietary fats.     

Suppression of apolipoprotein B secretion from HepG2 cells by glucosyl hesperidin

Our previous study has shown that a soluble hesperidin derivative, glucosyl hesperidin (G-hesperidin), preferentially lowers serum triglyceride (TG) level in hypertriglyceridemic subjects through the improvement of very low-density lipoprotein (VLDL) metabolic abnormality. G-Hesperidin has also been found to decrease an elevated serum apolipoprotein B (apo B) level in the hypertriglyceridemic subjects, suggesting a possibility that this compound suppresses excess VLDL secretion in the liver. In the present study, to gain a better understanding of possible mechanisms by which G-hesperidin lowers serum TG, we examined whether this derivative affects apo B secretion from HepG2 human hepatoma cells, a model of hepatic VLDL secretion. As a result, G-hesperidin significantly reduced apo B secretion from the oleate-stimulated HepG2 cells. Furthermore, G-hesperidin significantly suppressed apo B secretion only in the oleate-stimulated cells and failed to act on the cells incubated without oleate. In the oleate-stimulated cells, G-hesperidin significantly decreased cellular cholesteryl ester (CE), although it had no effect on cellular TG or free cholesterol amounts. Moreover, the oleate-stimulated cells had a decrease in cellular apo B amounts by G-hesperidin exposure. These findings indicate that G-hesperidin down-regulates the assembly of apo B-containing lipoproteins via the reduction of CE synthesis augmented with oleate and results in suppressing excess apo B secretion from the cells. This effect is speculated to be associated with the improvement of VLDL metabolic abnormality in hypertriglyceridemic subjects and considered as a mechanism of lowering serum TG.     

Different effects of zinc and copper deficiency on composition of plasma high density lipoproteins in rats

Male Sprague-Dawley rats (six per group) were fed an egg white-based diet containing 0 or 5 micrograms/g Cu with 1, 10, 100 or 1000 micrograms/g Zn. After 6 wk of feeding, the rats were killed, and the tissues were processed for trace element, lipid and lipoprotein analysis. Copper deficiency was associated with a higher concentration of plasma free cholesterol, high density lipoprotein (HDL) cholesterol and HDL apolipoproteins. Plasma total cholesterol was not significantly affected. No significant differences were noted in HDL lipid composition. However, HDL apo E and apo A-I concentrations were higher with copper deficiency. Lecithin:cholesterol acyltransferase (LCAT) was not affected in a consistent manner by copper status. Varying the amount of zinc in the diet did not produce significant changes in plasma total cholesterol, plasma free cholesterol, HDL cholesterol, or HDL apolipoprotein concentrations. However, HDL from zinc-deficient rats were enriched in free cholesterol and depleted in triglycerides. Furthermore, the concentration of HDL apo C increased as the level of dietary zinc increased.     

Catabolism of newly formed triglyceride-rich lipoproteins and serum high density lipoproteins in rats fed soybean phospholipid and soybean oil

Previous research has shown that serum cholesterol and apolipoprotein (apo) A-I were lower and serum apoB was higher in rats fed soybean phospholipid (PL) than in rats fed soybean oil. Secretion of cholesterol and apoA-I, but not apoB, from the liver and intestine was lower in rats fed soybean PL. In the present study catabolism of newly formed triglyceride (TG)-rich lipoproteins, from the liver and intestine, and of serum high density lipoproteins (HDL) were compared in rats fed soybean PL and in rats fed soybean oil. The following results were seen: Feeding of soybean PL was related to more TG and less cholesterol in intestinal lymph chylomicrons (CM) and hepatic very low density lipoproteins (VLDL) than was feeding of soybean oil. A lesser amount of the TG, labeled with [3H]oleate in CM and hepatic VLDL, was incorporated into the adipose tissue and muscle in vivo. The clearance of CM-TG from plasma was higher, but that of VLDL-TG and apoB labeled with [3H]lysine was lower. The catabolism of 125I-labeled HDL from the plasma was lower while hepatic uptake of 125I-labeled HDL, in vivo and in vitro, was higher. These results indicate that soybean PL modifies the catabolism of the respective serum lipoproteins. Therefore, we suggest that changes in both the catabolism and secretion of lipoproteins are responsible for the altered serum lipid and apolipoprotein patterns found in rats fed soybean PL.