In vitro transfer of apolipoproteins from plasma lipoproteins to artificial lipid particles

Our earlier studies in vivo revealed that artificial lipid particles (exo TG) in lipid emulsion acquire apolipoprotein C-II (apo C-II) from high density lipoprotein (HDL). Since the transfer of apo C-II to exo TG terminated within a short time after the intravenous injection of exo TG, it is likely that exo TG has a high affinity for apolipoprotein. This hypothesis has been investigated in vitro. Human plasma was incubated at 37 degrees C with or without a 10% emulsion of soybean oil for 5 min and 60 min. After the incubation, the plasma was separated into HDL, low density lipoprotein (LDL) and very low density lipoprotein (VLDL). Levels of apo C-II, C-III and E in each lipoprotein fraction were quantified. When the plasma was incubated without exo TG, the distribution of apo C-II and C-III in the lipoprotein fractions was unchanged after incubations for 5 and 60 min. However, when the plasma was incubated with exo TG, apo C-II and C-III in the HDL fraction decreased after a 5 min incubation, while those in the VLDL fraction increased. Apo E in each lipoprotein fraction did not change after 5- and 60-min incubations regardless of the presence or absence of exo TG.(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

Reduction in plasma apolipoprotein E and HDL1 levels in rats with essential fatty acid deficiency

Rats were fed linoleate- or triolein-supplemented total parenteral solutions by continuous intragastric infusion for 7 or 14 d to characterize plasma lipid and apolipoprotein (apo) levels, and the high density lipoprotein (HDL) profile associated with essential fatty acid deficiency (EFAD). Results indicate that plasma cholesterol and triglyceride levels tend to be lower with EFAD, whereas plasma levels of apolipoproteins E and B are lower and apo A-I levels are higher in EFAD animals. EFAD was also associated with 30% fewer apo E--enriched HDL1 particles and a decrease from 11.4 to 11.1 nm in the mean peak diameter of HDL (P less than 0.05). These observations emphasize the sensitivity of apo E content to alterations in plasma cholesterol level and suggest that cholesterol transport is decreased during EFAD in the rat.     

Compositional changes in plasma high-density lipoprotein particles in marginally zinc-deficient male rats

This study investigated the effect of zinc status on the lipid and apolipoprotein composition of high-density lipoproteins (HDL) in adult male rats fed a semipurified diet containing a marginal level (2.8 mg/kg) of Zn as compared with the pair-fed and ad libitum-fed controls given an adequate level (30.8 mg/kg) of Zn for 7-10 wk. Compositional and chromatographic analysis of HDL fraction showed that Zn deficiency significantly lowered the total amount of circulating HDL particles with no effect on the concentrations of total protein, triglyceride, phospholipid, and cholesterol. The ratios of free: esterified cholesterol remained the same for the three groups. Electrophoretic analysis of the apolipoprotein profile showed marked decreases in the relative contents of apolipoproteins E and C and an increase in apolipoprotein (apo) A-I with no significant change in apo A-VI. No apparent morphologic aberrations of HDL particles were observed. Such changes may significantly influence the transport and metabolism of cholesterol and may provide an explanation for altered cholesterol homeostasis in Zn deficiency.     

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.     

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.     

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.     

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.     

Interrelationship of plasma triglycerides and HDL size and composition in rats fed different dietary saturated fats

We investigated the relative effects of different dietary saturated fats on the size distribution, apolipoprotein (apo) and chemical composition of HDL in fasted rats. Male Sprague-Dawley rats (174 +/- 2 g) were fed diets containing 0.035% cholesterol and 16% fat (wt/wt) from corn oil (CO diet) or from 2% CO plus 14% butterfat (BF diet), beef tallow (BT diet), palm oil (PO diet) or coconut oil (CN diet) for 6 wk. Apparent lipid digestibility was significantly lower with the PO and BT diets vs. the CO, BF and CN diets. Plasma total cholesterol levels were significantly higher in rats fed the PO and BT diets than in rats fed the BF and CN diets but were not different among the PO-, BT- and CO-fed groups. Nondenaturing gradient gel electrophoresis immunoblot analysis indicated that HDL apo A-I and E resided on particles with significantly smaller modal diameters in rats fed all saturated fats compared with those fed the CO diet. Chemical analyses indicated that HDL generally contained proportionately less protein and more triglyceride, free cholesterol and apo E with saturated fat feeding than with CO diet feeding. Significantly higher plasma and VLDL triglyceride levels were noted with ingestion of the BT, PO or CN diet than with the CO diet. Butterfat feeding resulted in lower plasma triglycerides and HDL-esterified cholesterol than did feeding the other saturated fats. Very low density lipoprotein triglyceride concentrations were inversely correlated with HDL modal diameter of apo E containing lipoproteins (P less than 0.005). These data provide further evidence of the interrelationship of triglyceride and HDL metabolism and suggest that mechanisms independent of cholesterol ester transfer protein may mediate this response in rats.     

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.     

Studies on stroke-prone spontaneously hypertensive rats (SHRSP) fed a high-fat and high-cholesterol diet--changes in serum concentrations and distributions of apolipoproteins A-I, A-IV and E

The effects of a high-fat and high-cholesterol diet (HFC diet) on serum lipoproteins and apolipoproteins were studied in stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Kyo: Wistar rats (WKY). In particular, the changes in serum concentrations and distributions among lipoprotein fractions of apolipoproteins A-I, A-IV and E (apo A-I, A-IV and E) were investigated in detail. These apolipoproteins are the main protein constituents of high density lipoprotein (HDL) which is considered to be an anti-atherogenic factor and accounts for a large part of the serum lipoproteins in the rat. Serum lipoprotein fractions were isolated by stepwise density-gradient ultracentrifugation. The alterations in lipoprotein fractions and apolipoproteins in lipoprotein fractions were roughly estimated by native gradient polyacrylamide gel electrophoresis and sodium dodecyl sulfate (SDS)-gradient polyacrylamide gel electrophoresis. Next, the concentrations of apo A-I, A-IV and E in serum, serum lipoprotein fractions and serum lipoprotein-free fraction were measured by rocket immunoelectrophoresis according to the method of Laurell as modified by us. Cholesterol was enzymatically determined by a commercially available kit. The results obtained were as follows: 1) A remarkable increase in the very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) fractions was observed in WKY and SHRSP. This was associated with a remarkable increase in the cholesterol and apo B contents and with a significant increase in the apo E content. These changes in the VLDL and IDL fractions were more drastic in SHRSP than in WKY, which suggests the promotive effect of hypertension in SHRSP on the production of VLDL and IDL fractions.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

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)     

Small supplements of N-3 fatty acids change serum low density lipoprotein composition by decreasing phospholipid and apolipoprotein B concentrations in young adult women

Summary In order to investigate the effect of a short-term application of marine n-3 polyunsaturated fatty acids on the composition of serum very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL), nine women aged 29±4.2 years, following a diet with a SFA/MUFA/PUFA profile of 2.4/3/1, received supplements of six capsules daily, each capsule containing 0.137 g of n-3 fatty acids (14.5% eicosapentaenoic acid (EPA) and 8.9% docosahexaenoic acid (DHA)) for 10 d. Food consumption, assessed during two 10-days periods indicates that percentage contribution of SFA, MUFA, and PUFA to the daily energy intake did not change through the fish-oil supplementation period, but the daily consumption of n-3 fatty acids increased 2.3 times. N-3 fatty supplementation increased EPA and DHA percentages in serum phospholipids, but failed to decrease (p>0.05) the cholesterol and triglyceride concentration in serum LDL and HDL, although it did so in VLDL. In contrast, the lipoprotein-phospholipid and lipoprotein-protein concentrations were markedly affected, mainly in LDL and HDL (at least p<0.01). HDL and VLDL compositions were not affected but the total mass (lipid+protein in mg/dl) concentration of these lipoproteins significantly decreased (p<0.05), suggesting a lower number of these particles in circulating blood after the n-3 treatment. The LDL-cholesterol/LDL-apolipoprotein B ratio increased (p<0.01) reflecting a probable increase in LDL size. Following fish oil supplementation, LDL particles contained a significantly lower amount of phospholipids, which also suggests changes in the surface/core ratio of the average LDL. Changes in serum lipoprotein lipids did not significantly correlate with any dietary change other than the n-3 fatty acid increase. The results indicate that a 10-day application of a small supplement of n-3 change the LDL composition leading to less atherogenic LDL particles with lower phospholipid and apolipoprotein (Apo) B concentrations. Received: 15 May 1998, Accepted: 28 August 1998     

A solid dietary fat containing fish oil redistributes lipoprotein subclasses without increasing oxidative stress in men

There is a demand and need for healthy solid dietary fats. However, synthetic fats can be tailored to contain specific physiologic properties. Our goal was to design dietary solid test fats that would be both beneficial to the atherogenic lipid profile and stable against lipid peroxidation. Sixteen men (age 35-75 y) substituted 80 g of their normal dietary fat intake with test fat for two periods of 21 d each in a double-blind, randomized, crossover study. Although solid, both test fats were low in cholesterol-raising SFA. Test fat "F" contained 5 g/100 g long chain (n-3) fatty acids matched by oleic acid in test fat "O." Plasma total triacylglycerol (TAG), VLDL TAG, cholesterol in VLDL, and intermediate density lipoproteins (IDL) were lower (P < 0.05), whereas apolipoprotein (apo) B of the large LDL-2 (d = 1031-1042 g/L) subclass, and cholesterol of HDL(2b) subclass, were higher after intake of F than O fat (P < 0.05). There was no difference in the effect on in vivo oxidation measured as the ratio of plasma isoprostanes F(2) to arachidonic acid and urinary isoprostanes, whereas the vitamin E activity/plasma total lipids ratio was higher after intake of F than O (P = 0.008). In conclusion, a solid dietary fat containing (n-3) PUFA decreased plasma TAG, VLDL, and IDL cholesterol, and redistributed lipoprotein subclasses in LDL and HDL, with a higher concentration of the larger and less atherogenic subfractions. These changes took place without an increase in oxidative stress as measured by in vivo markers.     

Heritability of Serum Apolipoprotein Concentrations in Middle-Aged Japanese Twins

Background

Studies of the genetic and environmental influences on apolipoproteins have been conducted, but few have used data from Japanese twins. The aim of this study was to quantify and compare the genetic and environmental causes of individual differences in the serum concentrations of apolipoproteins in Japanese middle-aged twins.

Methods

Apo A-I, apo A-II, apo B, apo C-II, apo C-III, and apo E were studied. A total of 142 twin pairs, aged 45 through 65 years, were enrolled: 85 monozygotic pairs (59 male, 26 female) and 57 same-sexed dizygotic pairs (43 male, 14 female). The intraclass correlation coefficient and structural equation modeling were used to estimate the best-fitting model and heritability.

Results

Sixteen percent to 75% of the total variances of apo A-I, apo C-II, and apo C-III were attributable to genetic influence; apo A-I and apo C-II were influenced by dominant genetic factors. Twenty percent to 73% of the total variances of apo A-II, apo B, and apo E were attributable to additive genetic influence; apo B was clearly influenced by common environmental factors. Furthermore, the heritability of all apolipoproteins was higher among females than among males.

Conclusions

Genetic factors, including additive genetic effects (A) and dominant effects (D), influence apolipoprotein levels. However, a common environment does not influence the variances of these apolipoproteins, with the exception of apo B. Furthermore, the heritability of apolipoprotein phenotypes differs by sex.Key words: apolipoprotein, heritability, adult twins     

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.     

Changes in rat plasma apolipoproteins and lipoproteins during moderate protein deficiency: potential use in the assessment of nutritional status

To test apolipoprotein sensitivity as protein deficiency markers, concomitant evolution of plasma apolipoproteins (apo) and usual nutritional markers (transthyretin, albumin, transferrin) were followed during a 28-d protein restriction in young male Wistar rats. In addition, plasma lipids and chemical composition of lipoproteins were assayed by d 28. The control and the deficient groups were fed 18% and 6% casein diets, respectively. By d 28 the protein-deficient group exhibited hypotriglyceridemia resulting from the decrease in VLDL triacylglycerols; free cholesterol and phospholipids were increased, reflecting the increment in LDL-HLDL1. In plasma total lipoproteins, apo BH, AI and E were not different than controls in the deficient group. Apolipoprotein AIV decreased after d 14 and was significantly less than in controls at d 28. Apolipoprotein BI was considerably reduced by d 14 (43% less) and d 28 (52% less) compared with the control group. Apolipoproteins C + AII were significantly lower in the protein-deficient group by d 14 (43%). By d 28, VLDL apo C were decreased 60% by protein restriction. Transthyretin level was 20% lower in the protein-deficient group by d 7 but returned to control values by d 14. A moderately lower value was observed for albumin by d 7 and d 14 and for transferrin by d 28. These results indicate that, in this model, apo BI and C are more sensitive to protein depletion than usual nutritional markers.     

Studies on stroke-prone spontaneously hypertensive rats (SHRSP) fed a high-fat and high-cholesterol diet--effect of taurine on serum lipoprotein metabolism in hypercholesterolemic rats

It is well known that taurine, a final metabolite of sulfur-containing amino acids, plays an important role in bile acid metabolism and that it also has a moderately hypotensive effect. Moreover, it has recently been revealed that taurine shows a hypocholesterolemic effect in animals with experimentally induced hypercholesterolemia. However, the hypocholesterolemic mechanism remains unresolved. Stroke-prone spontaneously hypertensive rats (SHRSP) easily develop hypercholesterolemia when fed a high-fat and high-cholesterol diet (HFC diet). In our previous paper, we reported changes in the concentrations and distributions of serum lipoproteins and apolipoproteins in hypercholesterolemic SHRSP and Kyo: Wistar rats (WKY) induced by HFC feeding. In this paper, to elucidate the mechanism of the hypocholesterolemic effect of taurine, we investigated the effects of taurine on concentrations and distributions of serum lipoproteins and apolipoproteins in hypercholesterolemic SHRSP and WKY induced by HFC feeding. The results obtained were as follows: 1) The hypocholesterolemic effect of taurine in hypercholesterolemic SHRSP was remarkable in comparison with that in hypercholesterolemic WKY. 2) The hypocholesterolemic effect of taurine was mainly due to a marked suppression of extreme elevations of cholesterol contents in the VLDL and IDL fractions of both strains. This was associated with a decrease in the elevated contents of apo B and apo E which are major components of VLDL and IDL. This suppressive effect was more obvious in SHRSP than in WKY, which explains the greater hypocholesterolemic effect of taurine in SHRSP. It could be that, as a result of taurine administration, the catabolism of cholesterol to bile acid in the liver is accelerated, followed by a decrease of the hepatic cholesterol pool, resulting in a suppression of the synthesis and/or secretion of VLDL (beta-VLDL) in the liver. 3) The hypocholesterolemic effect of taurine was also observed in the LDL fractions of both strains, but the effect was not as strong as that observed in the VLDL and IDL fractions. This effect might be attributable to suppression of the synthesis and/or secretion of LDL in the liver and a decrease in the elevated content of apo E HDL (HDLc) which spans two density fractions (the LDL and HDL fractions). 4) In HDL fractions of both strains, the decreased content of apo E HDL (HDL1 and HDLc) was even lower, whereas the decreased apo A-I content in the HDL fraction of SHRSP was significantly restored and the cholesterol level was slightly elevated.(ABSTRACT TRUNCATED AT 400 WORDS)     

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.