Carbohydrate type and amount alter intravascular processing and catabolism of plasma lipoproteins in guinea pigs

To test the effects of exchanging dietary complex and simple carbohydrate for fat calories on lipoprotein metabolism, guinea pigs were fed two different fat/carbohydrate ratios: 2.5∶58% (w/w) or 25∶29% (w/w) with either sucrose or starch as the carbohydrate source. Animals fed high-fat had higher plasma low-density lipoprotein (LDL) and hepatic cholesterol concentrations than animals fed low-fat diets (P<0.01). The cholesteryl ester content per particle was higher, and the number of triacylglycerol (TAG) molecules was lower in very low density lipoprotein (VLDL) and LDL from animals fed high-fat diets. Intake of high-fat/sucrose resulted in higher plasma LDL concentrations than intake of high-fat/starch, and animals fed low-fat/starch had the highest plasma TAG concentrations associated with VLDL particles containing more TAG molecules, as well as a TAG-enriched LDL. The activity of plasma lecithin cholesteryl:acyl transferase (LCAT) was highest in animals fed high-fat/sucrose, and heart lipoprotein lipase (LPL) activity was higher in animals fed high-fat diets. Hepatic apoprotein B/E (apo B/E) receptor number (B_max) was increased 21% with low-fat diets (P<0.01). These results suggest that the hypercholesterolemia induced by high-fat and by sucrose intake are associated with a higher plasma LCAT activity which results in a cholesteryl ester-enriched VLDL which, by the action of LPL, might be more readily converted to LDL through the delipidation cascade leading to downregulation of hepatic apo B/E receptors. The hypertriglyceridemia associated with low-fat intake may result from increased production of VLDL TAG, which would explain the increased TAG content and the higher TAG/CE ratio of VLDL from animals fed the low-fat/starch diet.     

Soluble fiber and soybean protein reduce atherosclerotic lesions in guinea pigs. Sex and hormonal status determine lesion extension

These studies were undertaken to assess guinea pigs as potential models for early atherosclerosis development. For that purpose, male, female, and ovariectomized (to mimic menopause) guinea pigs were fed a control or a TEST diet for 12 wk. Differences between diets were the type of protein (60% casein/40% soybean vs. 100% soybean) and the type of fiber (12.5% cellulose vs. 2.5% cellulose/5% pectin/5% psyllium) for control and TEST diets, respectively. Diet had no effect on plasma cholesterol or triacylglycerol (TAG) concentrations; however, there were significant effects related to sex/hormonal status. Ovariectomized guinea pigs had higher plasma cholesterol and TAG concentrations than males or females (P<0.01). In contrast to effects on plasma lipids, hepatic cholesterol and TAG were 50% lower in the TEST groups (P<0.01) compared to controls. Low density lipoproteins (LDL) from guinea pigs fed the TEST diet had a lower number of cholesteryl ester (CE) molecules and a smaller diameter than LDL from controls. Atherosclerotic lesions were modulated by both diet (P<0.0001) and sex (P<0.0001). Guinea pigs fed the TEST diet had 25% less lesion extension whereas males had 20% larger occlusion of the arteries compared to both female and ovariectomized guinea pigs. Significant positive correlations were found between LDL CE and atherosclerotic lesions (r=0.495, P<0.05) and LDL size and fatty streak area (r=0.56, P<0.01). In addition, females fed the TEST diet had the lowest plasma and hepatic cholesterol concentrations, the smallest LDL particles, and the least atherosclerosis involvement compared to the other groups. These data indicate that dietary factors and sex/hormonal status play a role in determining plasma lipids and atherosclerosis in guinea pigs.     

Effects of dietary phenolic compounds on tocopherol, cholesterol, and fatty acids in rats

The effects of the phenolic compounds butylated hydroxytoluene (BHT), sesamin (S), curcumin (CU), and ferulic acid (FA) on plasma, liver, and lung concentrations of α- and γ-tocopherols (T), on plasma and liver cholesterol, and on the fatty acid composition of liver lipids were studied in male Sprague-Dawley rats. Test compounds were given to rats ad libitum for 4 wk at 4 g/kg diet, in a diet low but adequate in vitamin E (36 mg/kg of γ-T and 25 mg/kg of α-T) and containing 2 g/kg of cholesterol. BHT significantly reduced feed intake (P<0.05) and body weight and increased feed conversion ratio; S and BHT caused a significant enlargement of the liver (P<0.001), whereas CU and FA did not affect any of these parameters. The amount of liver lipids was significantly lowered by BHT (P<0.01) while the other substances reduced liver lipid concentrations but not significantly. Regarding effects on tocopherol levels, (i) feeding of BHT resulted in a significant elevation (P<0.001) of α-T in plasma, liver, and lung, while γ-T values remained unchanged; (ii) rats provided with the S diet had substantially higher γ-T levels (P<0.001) in plasma, liver, and lung, whereas α-T levels were not affected; (iii) administration of CU raised the concentration of α-T in the lung (P<0.01) but did not affect the plasma or liver values of any of the tocopherols; and (iv) FA had no effect on the levels of either homolog in the plasma, liver, or lung. The level of an unknown substance in the liver was significantly reduced by dietary BHT (P<0.001). BHT was the only compound that tended to increase total cholesterol (TC) in plasma, due to an elevation of cholesterol in the very low density lipoprotein + low density lipoprotein (VLDL+LDL) fraction. S and FA tended to lower plasma total and VLDL+LDL cholesterol concentrations, but the effect for CU was statistically significant (P<0.05). FA increased plasma high density lipoprotein cholesterol while the other compounds reduced it numerially, but not significantly. BHT, CU, and S reduced cholesterol levels in the liver TC (P<0.001) and percentages of TC in liver lipids (P<0.05). With regard to the fatty acid composition of liver lipids, S increased the n-6/n-3 and the 18∶3/20∶5 polyunsaturated fatty acids (PUFA) ratios, and BHT lowered total monounsaturated fatty acids and increased total PUFA (n−6+n−3). The effects of CU and FA on fatty acids were not highly significant. These results suggest some in vivo interactions between these phenolic compounds and tocopherols that may increase the bioavailability of vitamin E and decrease cholesterol in rats.     

Dietary menhaden, seal, and corn oils differentially affect lipid and Ex vivo eicosanoid and thiobarbituric acid-reactive substances generation in the guinea pig

This investigation was carried out to characterize the effects of specific dietary marine oils on tissue and plasma fatty acids and their capacity to generate metabolites (prostanoids, lipid peroxides). Young male guinea pigs were fed nonpurified diet (NP), or NP supplemented (10%, w/w) with menhaden fish oil (MO), harp seal oil (SLO), or corn oil (CO, control diet) for 23 to 28 d. Only the plasma showed significant n−3 polyunsaturated fatty acid (PUFA)-induced reductions in triacylglycerol (TAG) or total cholesterol concentration. Proportions of total n−3 PUFA in organs and plasma were elevated significantly in both MO and SLO dietary groups (relative to CO), and in all TAG fractions levels were significantly higher in MO-than SLO-fed animals. The two marine oil groups differed in their patterns of incorporation of eicosapentaenoic acid (EPA). In guinea pigs fed MO, the highest levels of EPA were in the plasma TAG, whereas in SLO-fed animals, maximal incorporation of EPA was in the heart polar lipids (PL). In both marine oil groups, the greatest increases in both docosahexaenoic acid (22∶6n−3, DHA) and docosapentaenoic acid (22∶5n−3, DPA) relative to the CO group, were in plasma TAG, although the highest proportions of DHA and DPA were in liver PL and heart TAG, respectively. In comparing the MO and SLO groups, the greatest difference in levels of DHA was in heart TAG (MO>SLO, P<0.005), and in levels of DPA was in heart PL (SLO>MO, P<0.0001). The only significant reduction in proportions of the major n−6 PUFA, arachidonic acid (AA), was in the heart PL of the SLO group (SLO>MO=CO, P<0.005). Marine oil feeding altered ex vivo generation of several prostanoid metabolites of AA, significantly decreasing thromboxane A₂ synthesis in homogenates of hearts and livers of guinea pigs fed MO and SLO, respectively (P<0.04 for both, relative to CO). Lipid peroxides were elevated to similar levels in MO- and SLO-fed animals in plasma, liver, and adipose tissue, but not in heart preparations. This study has shown that guinea pigs respond to dietary marine oils with increased organ and plasma n−3 PUFA, and changes in potential synthesis of metabolites. They also appear to respond to n−3 PUFA-enriched diets in a manner that is different from that of rats.     

Effect of dietary cholesterol on low density lipoprotein-receptor, 3-hydroxy-3-methylglutaryl-CoA reductase, and low density lipoprotein receptor-related protein mRNA expression in healthy humans

We investigated the possibility that dietary cholesterol downregulates the expression of low density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase genes of circulating mononuclear cells in vivo in healthy humans. We also studied the variations of the LDL receptor-related protein (LRP) gene in the same conditions. Dieters (n=5) were submitted to a 4-d fat restriction (mean cholesterol intake: 6±4 mg/d), followed by a 7-d cholesterol (a mean of 791±150 mg/d) supplementation. Controls (n=3) did not change their diet. During fat restriction, serum total and LDL cholesterol decreased significantly (P<0.05), and LDL receptor and HMG-CoA reductase mRNA copy numbers in mononuclear cells increased by 57 and 147%, respectively (P<0.05). After reintroducing cholesterol, serum cholesterol was stable whereas LDL receptor and HMG-CoA reductase mRNA decreased by 46 and 72% (P<0.05) and LRP mRNA increased by 59% (P<0.005). The changes in LDL receptor and HMG-CoA reductase mRNA abundance were correlated (r=+0.79, P=0.02) during cholesterol reintroduction as were LDL receptor and LRP mRNA levels, but negatively (r=−0.70, P=0.05). Also, 70% of the variability in LRP mRNA (P<0.005) was explained by dietary cholesterol. Thus, the basic mechanisms regulating cellular cholesterol content, the coordinate feedback repression of genes governing the synthesis and uptake of cholesterol, are operating in vivo in humans. However, serum cholesterol did not increase in response to dietary cholesterol, suggesting that these mechanisms may not play as predominant a role as previously believed in the short-term control of serum cholesterol in vivo in humans. A new finding is that LRP gene is also sensitive to dietary cholesterol, suggesting that it may participate in the control of serum cholesterol. Further in vivo studies in humans are warranted to explore the molecular mechanisms of the physiological response to dietary cholesterol in humans.     

Influence of Simvastatin on apoB-100 Secretion in Non-Obese Subjects with Mild Hypercholesterolemia

Statins decrease apoB-100-containing lipoproteins by increasing their fractional catabolic rates through LDL receptor-mediated uptake. Their influence on hepatic secretion of these lipoproteins is controversial. The objective of the study was to examine the influence of simvastatin on the secretion of apoB-100-containing lipoproteins in fasting non-obese subjects. Turnover of apoB-100-containing lipoproteins was investigated using stable isotope-labeled tracers. Multicompartmental modeling was used to derive kinetic parameters. Eight male subjects (BMI 25 ± 3 kg/m²) with mild hypercholesterolemia (LDL cholesterol 135 ± 30 mg/dL) and normal triglycerides (111 ± 44 mg/dL) were examined under no treatment (A), under chronic treatment with simvastatin 40 mg/day (B) and after an acute-on-chronic dosage of 80 mg simvastatin under chronic simvastatin treatment (C). Lipoprotein concentrations changed as expected under 40 mg/day simvastatin. Fractional catabolic rates increased in IDL and LDL but not in VLDL fractions versus control [VLDL +35% in B (n.s.) and +21% in C (n.s.); IDL +169% in B (P = 0.08) and +187% in C (P = 0.032); LDL +87% in B (P = 0.025) and +133% in C (P = 0.025)]. Chronic (B) and acute-on-chronic simvastatin treatment (C) did not affect lipoprotein production rates [VLDL −8 and −13%, IDL +47 and +38%, and LDL +19 and +30% in B and C, respectively (all comparisons n.s.)]. The data indicate that simvastatin does not influence the secretion of apoB-100-containing lipoproteins in non-obese subjects with near-normal LDL cholesterol concentrations.     

Effects of dietary saturated fat on erucic acid induced myocardial lipidosis in rats

Male Sprague-Dawley rats were fed for one week diets containing 20% by weight fat/oil mixtures with different levels of erucic acid (22∶1n−9) (∼2.5 or 9%) and total saturated fatty acids (∼8 or 35%). Corn oil and high erucic acid rapeseed (HEAR) oil were fed as controls. The same hearts were evaluated histologically using oil red O staining and chemically for cardiac triacylglycerol (TAG) and 22∶1n−9 content in cardiac TAG to compare the three methods for assessing lipid accumulation in rat hearts. Rats fed corn oil showed trace myocardial lipidosis by staining, and a cardiac TAG content of 3.6 mg/g wet weight in the absence of dietary 22∶1n−9. An increase in dietary 22∶1n−9 resulted in significantly increased myocardial lipidosis as assessed histologically and by an accumulation of 22∶1n−9 in heart lipids; there was no increase in cardiac TAG except when HEAR oil was fed. An increase in saturated fatty acids showed no changes in myocardial lipid content assessed histologically, the content of cardiac TAG or the 22∶1n−9 content of TAG at either 2.5 or 9% dietary 22∶1n−9. The histological staining method was more significantly correlated to 22∶1n−9 in cardiac TAG (r=0.49;P<0.001) than to total cardiac TAG (r=0.40;P<0.05). The 22∶1n−9 content was highest in cardiac TAG and free fatty acids. Among the cardiac phospholipids, the highest incorporation was observed into phosphatidylserine, followed by sphingomyelin. With the addition of saturated fat, the fatty acid composition showed decreased accumulation of 22∶1n−9 and increased levels of arachidonic and docosahexaenoic acids in most cardiac phospholipids, despite decreased dietary concentrations of their precursor fatty acids, linoleic and linolenic acids.     

Hepatic lipid characteristics and histopathology of laying hens fed CLA or n−3 fatty acids

The effect of dietary CLA and n−3 PUFA on hepatic TAG accumulation, histopathology, and FA incorporation in lipid classes by laying chickens was investigated. One hundred twenty 30-wk-old single-comb white leghorn laying hens were distributed randomly to four treatments (3 replications of 10 birds) and were fed diets containing CLA and animal fat (Diet I), 18∶3n−3 (Diet II), or long-chain n−3 FA (Diet III). A sunflower oil (n−6 FA)-based diet was the control. Feeding Diet I resulted in an increase in hepatic total lipids (P<0.05). The liver TAG content was 32.2, 18.9, 29.4, and 18.7 mg/g for hens fed Diet I, Diet II, Diet III, and the control diet, respectively (P<0.05). The serum TAG was lowest in bilds fed Diet II (P<0.05). Diet I resulted in an increase in the total number of fat vacuoles and lipid infiltration in hepatocytes (P<0.05). The number of cells with 75% or higher lipid vacuolation was observed only in birds fed Diet I. Feeding diets containing CLA resulted in an increase in the content of the c9,t11 CLA isomer in liver TAG and PC (P<0.05). No difference was observed in the CLA concentration of hepatic PE fractions. The content of DHA (22∶6n−3) was higher in the TAG, PC, and PE of hens fed Diet II and Diet III than Diet I and the control (P<0.05). Feeding CLA resulted in an increase in total saturated FA in the TAG and PC fractions (P<0.05). Long-term feeding of CLA in laying birds leads to an increase in liver TAG and may predispose birds to fatty liver hemorrhagic syndrome.     

Changes in Plasma LDL and HDL Composition in Patients Undergoing Cardiac Surgery

Changes of lipoprotein composition have been mainly reported in conditions of sepsis. This study characterized compositional changes in LDL and HDL during the acute phase response following cardiac surgery with cardiopulmonary bypass. Twenty-one patients undergoing cardiac surgery were included in this study. Blood samples were drawn before operation and on day 2 post-surgery. In parallel to plasma lipids and antioxidant status, lipoproteins were analyzed for lipid, apolipoprotein (apo), hydroperoxide and alpha-tocopherol content. Beyond decreases in lipid concentrations and antioxidant defenses, cardiac surgery induced substantial modifications in plasma lipoproteins. ApoB decrease in LDL fraction (−46%; P < 0.0001) reflected a marked reduction in the circulating particle number. LDL cholesteryl ester content relative to apoB concentration remained unchanged post-surgery while triglyceride (+113%; P < 0.001), free cholesterol (+22%; P < 0.05) and phospholipid (+23%; P < 0.025) were raised relative to apoB indicating increased particle size. In HDL, an abrupt rise of apoSAA (P < 0.05) was observed together with a decrease of apoA1 (−22%; P < 0.005). Cholesteryl ester content in HDL fraction decreased in parallel to apoA1 concentration while triglycerides, free cholesterol and phospholipids increased relative to apoA1. In contrast to unchanged alpha-tocopherol content, hydroperoxide content was increased in LDL and HDL. By comparison to sepsis, cardiac surgery induces a comparable reduction in circulating LDL but a more limited decrease in HDL particles. Furthermore, in contrast, cardiac surgery induces an increase in polar and non-polar lipids, as well as of particle size in both LDL and HDL. M. Hacquebard is recipient of a fellowship from the Danone Institute, Belgium.     

Chylomicron and VLDL TAG structures and postprandial lipid response induced by lard and modified lard

Alterations in chylomicron and VLDL TAG and the magnitude of postprandial lipemia were studied in healthy volunteers after two meals of equal FA composition but different TAG-FA positional distribution. Molecular level information of individual lipoprotein TAG regioisomers was obtained with a tandem MS method. The incremental area under the response curve of VLDL TAG was large (P=0.021) after modified lard than after lard. In plasma TAG, the difference did not quite reach statistical significance (P=0.086). In general, there were less TAG with palmitic acid in the sn-2 position and more TAG with oleic acid in the sn-2 position in chylomicrons than in fat ingested. From 1.5 to 8 h postprandially, the proportion of individual chylomicron TAG was constant or influenced by TAG M.W. VLDL TAG regioisomerism was similar regardless of the positional distribution of fat ingested. Significant alterations were seen in VLDL TAG FA, in M.W. fractions, and in individual regioisomers with respect to time. The TAG sn-14∶0-18∶1-18∶1+sn-18∶1-18∶1-14∶0, sn-16∶0-16∶1-18∶1+sn-18∶1-16∶1-16∶0, and sn-16∶1-18∶1-18∶1+sn-18∶1-18∶1-16∶1 decreased (P<0.05); and sn-16∶0-16∶0-18∶2+sn-18∶2-16∶0-16∶0, sn-16∶0-16∶0-18∶1+sn-18∶1-16∶0-16∶0, sn-16∶0-18∶1-16∶0, and sn-16∶0-18∶1-18∶2+sn-18∶2-18∶1-16∶0 increased (P<0.05) after both meals. In conclusion, positional distribution of TAG FA was found to affect postprandial lipid metabolism in healthy normolipidemic subjects.     

Regulation of very low density lipoprotein apo B metabolism by dietary fat saturation and chain length in the guinea pig

Studies investigated the effects of dietary fatty acid composition and saturation on the regulation of very low density lipoprotein (VLDL) apo B flux, clearance, and conversion to low density lipoprotein (LDL) in guinea pigs fed semipurified diets containing 15% (w/w) corn oil (CO), lard (LA), or palm kernel oil (PK). Plasma cholesterol levels were highest with dietary PK (3.1±1.0 mmol/L) followed by LA (2.4±0.4 mmol/L) and CO (1.6±0.4 mmol/L) intake. VLDL particles were larger (P<0.05) in the LA (78±7 nm) and PK (69±10 nm) groups compared to animals fed CO (49±5 nm). VLDL-apo B fractional catabolic rates (FCR) were highest in guinea pigs fed the LA diet (P<0.05) and VLDL apo B flux, estimated from VLDL ¹²⁵I-apo B turnover kinetics, were higher in LA compared to PK or CO fed guinea pigs. In the case of PK consumption, the kinetic estimates of VLDL apo B flux significantly underestimated rates compared to direct VLDL apo B secretion measurements and LDL turnover analyses. These data demonstrate that differences in the composition and amount of saturated fatty acids have differential effects on VLDL apo B flux, catabolism, and conversion to LDL which, together with changes in LDL receptor-mediated catabolism, determine plasma LDL cholesterol levels in guinea pigs. The data also indicate that kinetic analysis of VLDL metabolism in PK fed animals is inaccurate possibly due to the presence of a small, nonequilibrating pool of newly synthesized VLDL which is rapidly converted to LDL.     

Dose-Dependent Effects of Docosahexaenoic Acid Supplementation on Blood Lipids in Statin-Treated Hyperlipidaemic Subjects

The objective of the study was to evaluate potential benefits of docosahexaenoic acid (DHA) rich fish oil supplementation as an adjunct to statin therapy for hyperlipidaemia. A total of 45 hyperlipidaemic patients on stable statin therapy with persistent elevation of plasma triglycerides (averaging 2.2 mmol/L) were randomised to take 4 g/day (n = 15) or 8 g/day (n = 15) of tuna oil or olive oil (placebo, n = 15) for 6 months. Plasma lipids, blood pressure and arterial compliance were assessed initially and after 3 and 6 months in 40 subjects who completed the trial. Plasma triglycerides were reduced 27% by 8 g/day DHA-rich fish oil (P < 0.05) but not by 4 g/day when compared with the placebo and this reduction was achieved by 3 months and was sustained at 6 months. Even though total cholesterol was already well controlled by the statin treatment (mean initial level 4.5 mmol/L), there was a further dose-dependent reduction with fish oil supplementation (r = −0.344, P < 0.05). The extent of total cholesterol reduction correlated (r = −0.44) with the initial total cholesterol levels (P < 0.005). In the subset with initial plasma cholesterol above 3.8 mmol/L, plasma very low density lipoprotein (VLDL), intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) were isolated and assayed for cholesterol and apolipoprotein B (apoB) at the commencement of the trial and at 3 months of intervention. Fish oil tended to lower cholesterol and apoB in VLDL and raise both in LDL. There were no changes in IDL cholesterol, IDL apoB and high-density lipoprotein cholesterol. The results demonstrate that DHA-rich fish oil supplementation (2.16 g DHA/day) can improve plasma lipids in a dose-dependent manner in patients taking statins and these changes were achieved by 3 months. Fish oil in addition to statin therapy may be preferable to drug combinations for the treatment of combined hyperlipidaemia.     

Electronegative Low-Density Lipoprotein is Associated with Dense Low-Density Lipoprotein in Subjects with Different Levels of Cardiovascular Risk

Dyslipidemias and physicochemical changes in low-density lipoprotein (LDL) are very important factors for the development of coronary artery disease (CAD). However, pathophysiological properties of electronegative low-density lipoprotein [LDL(−)] remain a controversial issue. Our objective was to investigate LDL(−) content in LDL and its subfractions (phenotypes A and B) of subjects with different cardiovascular risk. Seventy-three subjects were randomized into three groups: normolipidemic (N; n = 30) and hypercholesterolemic (HC; n = 33) subjects and patients with CAD (n = 10). After fasting, blood samples were collected and total, dense and light LDL were isolated. LDL(−) content in total LDL and its subfractions was determined by ELISA. LDL(−) content in total LDL was lower in the N group as compared to the HC (P < 0.001) and CAD (P = 0.006) groups. In the total sample and in those of the N, HC, and CAD groups, LDL(−) content in dense LDL was higher than in light LDL (P = 0.001, 0.001, 0.001, and 0.033, respectively) The impact of LDL(−) on cardiovascular risk was reinforced when LDL(−) content in LDL showed itself to have a positive association with total cholesterol (β = 0.003; P < 0.001), LDL-C (β = 0.003; p < 0.001), and non-HDL-C (β = 0.003; P < 0.001) and a negative association with HDL-C (β = −0.32; P = 0.04). Therefore, LDL(−) is an important biomarker that showed association with the lipid profile and the level of cardiovascular risk.     

Comparison of the effect of the amount and degree of unsaturation of dietary fat on plasma low density lipoproteins in vervet monkeys

The effects of the degree of unsaturation and of the amount of dietary fat on low density lipoprotein (LDL) concentration and composition were determined in vervet monkeys. Diets with fat contents of 41, 31 and 18% energy, each with a low and a high polyunsaturated to saturated fatty acid ratio (P/S; 0.27–0.38 and 1.13–1.47) were fed to six female vervet monkeys for two months. Another six females were given a low fat, high P/S diet for the same period of time, to serve as a reference. The cholesterol contents of the diets were low (21–33 mg per day) and relatively constant. LDL cholesterol concentrations decreased significantly (P≤0.01) when the dietary fat content decreased from 31 to 18% of energy. The dietary P/S ratio only affected LDL cholesterol concentrations during moderate (31% of energy) fat intake, where LDL cholesterol increased (P≤0.01) with a decrease in dietary P/S. Substantial individual variations were observed in LDL cholesterol concentration responses to dietary fat changes. The changes in LDL cholesterol concentrations were the result of changes in the concentration of LDL particles, as the molecular composition did not differ significantly between dietary periods. The high density lipoprotein choelsterol and the plasma triacylglycerol concentrations were not influenced by the dietary fat changes. During the high P/S diets, the percentage of 18∶2 (linoleic acid) increased (P≤0.01) and that of 18∶1 (oleic acid) decreased (P≤0.01) in LDL esterified cholesterol, as compared to the low P/S diets. In adipose tissue triacylglycerol the percentage of 18∶2 was three times higher (P≤0.01) during the high P/S diets than during the low P/S diets. A decrease in the amount of dietary fat (from 31 to 18% of energy) was associated with an increase in the percentage of 18∶1 in LDL esterified cholesterol.     

Type 1 diabetes compromises plasma arachidonic and docosahexaenoic acids in newborn babies

The activity of Δ6- and Δ5-desaturase, enzymes required for the synthesis of AA and DHA, are impaired in human and experimental diabetes. We have investigated whether neonates of type 1 diabetic women have compromised plasma AA and DHA at birth. Cord blood was obtained from healthy babies born to mothers with (n=31) and without (n=59) type 1 diabetes. FA composition of plasma choline phosphoglycerides (CPG), TG, and cholesterol esters (CE) was assayed. The neonates of the diabetics had lower levels of AA (20∶4n−6, P<0.0001), adrenic acid (22∶4n−6, P<0.01), Σn−6 metabolites (P<0.0001), docosapentaenoic acid (22∶5n−3, P<0.0001), DHA (22∶6n−3, P<0.0001), Σn−3 (P<0.0001), and Σn−3 metabolites (P<0.0001) in CPG compared with the corresponding babies of the nondiabetic mothers. Similarly, they had lower levels of AA (P<0.05), Σn−6 metabolites (P<0.05), DHA (P<0.0001), and Σn−3 metabolites (P<0.01) in plasma CE. There was also a nonsignificant reduction of AA and DHA in TG in the babies of the diabetic group. The current investigation indicates that healthy neonates born to mothers with type 1 diabetes have highly compromised levels of AA and DHA. These nutrients are of critical importance for neurovisual and vascular system development. In poorly controlled maternal diabetes, it is conceivable that the relative “insufficiency” of AA and DHA may exacerbate speech and reading impairments, behavioral disorders, suboptimal performance on developmental tests, and lower IQ, which have been reported in some children born to mothers with type 1 diabetes mellitus. Further studies are needed to understand the underlying mechanism for this biochemical abnormality and its implications for fetal and infant development.     

Correlation of suppressed linoleic acid metabolism with the hypocholesterolemic action of eritadenine in rats

The dose-dependent effects of dietary eritadenine on the metabolism of linoleic acid and on the plasma cholesterol concentration were investigated to clarify the mechanism of the hypocholesterolemic action of eritadenine in rats. Rats were fed control or eritadenine-supplemented (2 to 20 mg/kg) diets for 14 d. Eritadenine supplementation significantly decreased both the plasma cholesterol concentration and the 20∶4n−6/18∶2n−6 ratio of liver microsomal and plasma phosphatidylcholine (PC) in a dose-dependent manner. Eritadenine was also found to decrease the activity of Δ6 desaturase in liver microsomes; these was significant correlation between the Δ6-desaturase activity and the 20∶4n−6/18∶2n−6 ratio in the PC of liver microsomes (r=0.989, P<0.001) or plasma (r=0.986, P<0.001). Certain plasma PC molecular species, as represented by 16:0-18:2, were increased by eritadenine in a dose-dependent manner, and certain plasma PC molecular species, as represented by 18:0-20:4, were conversely decreased by eritadenine. There was a significant correlation between the plasma total cholesterol concentration and the proportion of the sum of plasma PC molecular species which contain 18:1 or 18:2 in the sn-2 position. These results support the idea that the suppression of linoleic acid metabolism by eritadenine might be associated with the hypocholesterolemic action of eritadenine.     

Positional distribution of decanoic acid: Effect on chylomicron and VLDL TAG structures and postprandial lipemia

Although medium-chain FA (MCFA) are mainly absorbed via the portal venous system, they are also incorporated into chylomicron TAG; therefore, the positional distribution of MCFA in TAG is likely to affect their metabolic fate. We studied chylomicron and VLDL TAG structures, as well as the magnitude of postprandial lipemia, after two oral fat loads containing decanoic acid (10∶0) predominantly at the sn-1(3),2 (MML) or at the sn-1,3 positions (MLM) of TAG in a randomized, double-blind, crossover clinical trial with 10 healthy, normal-weight volunteers. An MS-MS method was used to analyze TAG regioisomers. The position of decanoic acid in chylomicron TAG reflected its position in the TAG ingested, and TAG with none, one, two, or three decanoic acid residues were detected after ingestion of both fats. More (P<0.05) 30∶0 and 38∶1 TAG (acyl carbons:double bonds) and fewer 46∶5, 54∶5 and 54∶4 TAG were found in chylomicrons after ingestion of MML than after MLM. The VLDL TAG composition did not differ between the fat loads but did change (P<0.05) 2 to 6 h after ingestion of both fats. No statistical differences were seen between the fat loads in areas under the plasma, chylomicron, or VLDL TAG response curves or in FFA concentrations. Thus, the positional distribution of MCFA in TAG affects their metabolic, fate, but the magnitude of postprandial lipemia does not seem to be dependent on the positional distribution of MCFA in the ingested fat.     

Effects of dietary defatted squid on cholesterol metabolism and hepatic lipogenesis in rats

Male Sprague-Dawley rats were fed a cholesterol-free (Exp. 1) or cholesterol-supplemented (Exp. 2) diet containing 20% casein (control group) or 15% defatted squid and 5% casein (defatted squid group), as protein, for 14 d. Serum and hepatic cholesterol concentrations were lower in rats fed defatted squid than in those fed casein in both cholesterol-free (−20%, P<0.05 and −15%, P<0.05, respectively) and cholesterol-supplemented (−25%, P<0.05 and −15%, P<0.05, respectively) diets. Hepatic triglyceride concentration was lower in the defatted squid than in the control groups in both cholesterol-free (−51%, P<0.05) and cholesterol-supplemented diets (−38%, P<0.01). The activities of cytosolic fatty acid synthase and the NADPH-generating enzymes, malic enzyme and glucose-6-phosphate dehydrogenase, in the liver were lower in the defatted squid than in the control groups in both cholesterol-free (−21%, P<0.01, −33%, P<0.05, and −33%, P<0.01, respectively) and cholesterol-supplemented diets (−34%, P<0.05, −57%, P<0.05, and −67%, P<0.05, respectively). The activity of mitochondrial carnitine palmitoyltransferase in the liver was comparable between the control and defatted squid groups. The activity of Mg²⁺-dependent phosphatidate phosphohydrolase in the liver cytosol was lower in the defatted squid (−9%, P<0.05) than in the control groups only in the cholesterol-free diet. Fecal excretion of total steroids was stimulated by the feeding of defatted squid in both cholesterol-free (+77%, P<0.005) and cholesterol-supplemented diets (+29%, P<0.01). These results suggest that the nonlipid fraction of squid exerts a hypocholesterolemic effect by increasing the excretion of total steroids in feces. The fraction also induces a triglyceride-lowering activity in the liver by decreasing hepatic lipogenesis.     

Effect of n−3 fatty acid-rich fish oil supplementation on the oxidation of low density lipoproteins

This study was aimed at determining the effect of fish oil supplementation on copper-catalyzed oxidation of low density lipoproteins (LDL) from nine hypertriglyceridemic human subjects. A rapid headspace gas chromatographic method was used to measure the volatile oxidation products from LDL. Propanal and hexanal were the major volatile products formed in the oxidation of n−3 and n−6 polyunsaturated fatty acids (PUFA), respectively. Fish oil supplementation resulted in a significant increase in propanal formation from 3.7 to 13.4 nmol/mL LDL (P<0.01); it also resulted in small decreases in pentanal formation from 14.7 to 11.4 nmol/mL LDL and in hexanal formation from 138 to 108 nmol/mL LDL (P<0.05). The changes in peroxidation products paralleled the changes in LDL composition, which showed a significant increase in n−3 PUFA from 3.2 to 14.6% (P<0.01) and a decrease in n−6 PUFA from 43.7 to 35.0% (P<0.05). Propanal formation was highly and significantly correlated with n−3 PUFA content (r=0.950,P<0.001). Since total volatiles remained unchanged, this indicated that the two groups of LDL samples did not differ in overall oxidative susceptibility. Although fish oil intake did not alter the oxidative susceptibility of LDL, the chemically modified LDL particles generated a distinct pattern of volatile oxidation products that reflected changes in their fatty acid composition.     

Effect of Diacylglycerol on Postprandial Serum Triacylglycerol Concentration: A Meta-analysis

Diacylglycerol (DAG) supplementation has been shown to be associated with the reduction of postprandial triacylglycerol (TAG) concentration, although the extent of the association is uncertain. We quantitatively examined the effect of dietary DAG on postprandial serum TAG concentration by conducting a meta-analysis of randomized controlled trials. Potential papers were initially searched for in the electronic databases of Medline, Embase and Cochrane library. Inclusion criteria required the trial to be randomized with DAG as the treatment group, and TAG as the control group. Information was extracted independently by two investigators and the effect of DAG on postprandial TAG concentration was examined in Review Manager 4.2. Seven papers were included in the statistic pooling. DAG supplementation reduced the increment of postprandial TAG concentration significantly at postprandial 2 h (Weighted mean difference (WMD) −0.07 mmol/L; 95% CI −0.13 to 0.00 mmol/L; P = 0.05), 4 h (WMD −0.15 mmol/L; 95% CI −0.24 to −0.06 mmol/L; P = 0.002) and 6 h (WMD −0.14 mmol/L; 95% CI −0.23 to −0.05 mmol/L; P = 0.002). Linear regression showed that the effect of DAG was positively correlated with the daily dosage at 2 h (P = 0.095) and 6 h (P = 0.053) after lipid loading. In conclusion, compared with TAG oil, DAG reduced the postprandial serum TAG concentration at 2 h, 4 h and 6 h postprandial and was positively correlated with daily dosage.