Dietary linoleic acid-induced hypercholesterolemia and accumulation of very light HDL in steers

This experiment was designed to study the effects in fattening steers of n−6 PUFA supplementation on the plasma distribution and chemical composition of major lipoproteins (TG-rich lipoproteins: d<1.006 g/mL; intermediate density lipoproteins + LDL: 1.019<d<1.060 g/mL; light HDL: 1.060<d<1.091 g/mL; and heavy HDL: 1.091<d<1.180 g/mL). For a period of 70 d, animals [454±20 d; 528±36 kg (mean±SD)] were given a control diet (diet C, n=6) consisting of hay and concentrate mixture (54 and 46% of diet dry matter, respectively) or the same diet supplemented with sunflower oil (4% of dry matter), given either as crushed seeds (diet S, n=6) or as free oil continuously infused into the duodenum through a chronic canula to avoid ruminal PUFA hydrogenation (diet O, n=6). Plasma lipids increased in steers given diet S (×1.4, P<0.05) and diet O (×2.3, P<0.05), leading to hyperphospholipemia and hypercholesterolemia. With diet S, hypercholesterolemia was associated with higher levels of light (×1.4, P<0.05) and heavy HDL (×1.3, NS). With diet O, it was linked to higher levels of light HDL (×1.8, P<0.005) and to very light HDL accumulation within density limits of 1.019 to 1.060 g/mL, as demonstrated by the apolipoprotein A-I profile. Diet O favored incorporation of 18∶2n−6 into polar (×2.2, P<0.05) and neutral lipids (×1.5 to ×8, P<0.05) at the expense of SFA, MUFA, and n−3 PUFA. Thus, protection of dietary PUFA against ruminal hydrogenation allowed them to accumulate in plasma lipoproteins, but the effects of hypercholesterolemia on animal health linked to very light HDL accumulation remain to be elucidated.     

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.     

Diminished macrophage cholesterol removal rate by the altered HDL metabolism in the Nagase analbuminemic rat

Dyslipoproteinemia of the Nagase analbuminemic rat (NAR) is characterized by elevated concentrations of VLDL and LDL attributed to increased rates of liver lipoprotein synthesis. Increased lysophosphatidylcholine (LPC) in NAR HDL has been attributed to high plasma LCAT activity. We show here that, as compared with Sprague-Dawley rats (SDR), NAR plasma triacylglycerol (TAG), total cholesterol (TC), HDL TAG, protein, total phospholipids (PL), LPC, and PS are increased. These alterations rendered the NAR HDL particle more susceptible to the activity of the enzyme hepatic lipoprotein lipase (HL), which otherwise was unaltered in our study. Fractional catabolic rates in blood of the autologous ¹²⁵I-apoHDL (median and lower quartile values), were, respectively, 0.231 and 1.645 (n=10) in NAR as compared with 0.140 and 0.109 (n=10) in SDR (P=0.012), corresponding to synthesis rates of HDL protein of 89.8±33.7 mg/d in NAR and 17.4±6.5 mg/d in SDR (P=0.0122). Furthermore, Swiss mouse macrophage free-cholesterol (FC) efflux rates, measured as the percent [¹⁴C]-cholesterol efflux/6 h, were 8.2±2.3 (n=9) in NAR HDL and 11.2±3.2 (n=10) in SDR HDL (P=0.03). Therefore, in NAR the modification of the HDL composition slows down the cell FC efflux rate, and together with the increased rate of plasma HDL metabolism influences the reverse cholesterol transport system.     

Vitamin D and Evening Primrose Oil Administration Improve Glycemia and Lipid Profiles in Women with Gestational Diabetes

Limited data are available assessing the effects of vitamin D and evening primrose oil (EPO) administration on markers of insulin resistance and lipid concentrations in gestational diabetes mellitus (GDM). This study was designed to evaluate the effects of vitamin D and EPO administration on insulin resistance and lipid concentrations among women with GDM. In this prospective randomized, double‐blind, placebo‐controlled clinical trial, 60 participants with GDM were divided into 2 groups of either 1000 IU vitamin D3 and 1000 mg EPO or placebo for 6 weeks. At the beginning and end of the study, fasting blood samples were obtained from the participants to measure related variables. After 6 weeks of intervention, changes in fasting plasma glucose (?3.6 ± 7.5 vs. +1.5 ± 11.4 mg/dL, P = 0.04), serum insulin concentrations (?2.0 ± 5.3 vs. +4.6 ± 10.7 µIU/mL, P = 0.004), homeostasis model of assessment (HOMA) insulin resistance (?0.5 ± 1.1 vs. +1.1 ± 2.5, P = 0.003), HOMA‐B cell function (?7.7 ± 23.3 vs. +17.4 ± 42.9, P = 0.007) and the quantitative insulin sensitivity check index (+0.01 ± 0.02 vs. ?0.01 ± 0.02, P = 0.007) in the vitamin D plus EPO group were significantly different from the placebo group. In addition, compared with the placebo, vitamin D and EPO supplementation resulted in significant reductions in serum TAG (?20.0 ± 54.3 vs. +34.3 ± 38.2 mg/dL, P < 0.001), VLDL (?4.0 ± 10.9 vs. +6.9 ± 7.6 mg/dL, P < 0.001), TC (?22.1 ± 32.6 vs. +5.3 ± 20.1 mg/dL, P < 0.001), LDL concentrations (?18.0 ± 25.5 vs. +1.8 ± 15.7 mg/dL, P = 0.001) and TC/HDL (?0.3 ± 0.4 vs. +0.3 ± 0.5 mg/dL, P < 0.001). We did not observe any significant effect of vitamin D and EPO supplementation on serum HDL concentrations. Clinical trial registration number: http://www.irct.ir : IRCT201509115623N52.     

Effect of fish oil on cancer cachexia and host liver metabolism in rats with prostate tumors

The aim of this study was to investigate whether tumor-induced cachexia and aberrations in host liver metabolism, induced by the MAT-LyLu variant of the Dunning prostate tumor, could be prevented by ω3 fatty acids from fish oil. On day 0, adult Copenhagen-Fisher rats fed normal chowad libitum were inoculated with 10⁶ MAT-LyLu cells (n=14) or saline (n=9). On day 7, when tumors were palpable, four tumor-bearing (TB) and four nontumorbearing (NTB) rats were put on isocaloric diets with 50% of total energy as fish oil. The introduction of fish oil-enriched diets caused a reduction in energy intake to less than half of the energy intake by animals fed normal diets during days 7–14 (difference by dietary group: NTB,P<0.001; TB,P<0.001). During days 14–21, energy intake in fish oil-fed animals returned to approximately 75% of energy intake by animals fed normal diets (difference by dietary group: NTB,P<0.003; TB,P=0.001). Carcass weight of animals on day 21, when the study was terminated, was significantly related to initial weight (P=0.05) and mean food intake during the study (P=0.01). When data were adjusted for these variables using analysis of covariance, with NTB animals on normal diets being the reference group, significant loss of carcass weight was observed in TB animals on normal diets only (mean ±SEM 58±10 g loss,P<0.001), but not in TB animals on fish oil diets (8±18 g loss,P=0.67). This positive effect of fish oil diets on carcass weight in TB animals was statistically significant (50±19 g,P<0.02), implicating that the fish oil enriched diet inhibited tumor-induced weight loss by more than 85%. No effect of fish oil diets on tumor growth was detected. In all TB animals, regardless of diet, hepatic [P_i]/adenosine triphosphate] ratios measured by³¹P magnetic resonance spectroscopy (MRS)in vivo andin vitro were elevated, and absolute concentrations of phosphocholine, glycerophosphocho-line, glycerophosphoethanolamine and glucose-6-phosphate as determined by³¹P MRSin vitro were reduced. Ultrastructural studies of liver tissue revealed increased numbers of mitochondria and increased amounts of endoplasmic reticulum in the host liver of TB animals, without differences between dietary group. In conclusion, fish oil supplementation partially inhibited MAT-LyLu tumor-induced cachexia, but did not prevent the majority of³¹P MRS-detectable alterations in host liver metabolism.     

Soy protein containing isoflavones favorably influences macrophage lipoprotein metabolism but not the development of atherosclerosis in CETP transgenic mice

The possibility that soy protein containing isoflavones influences the development of experimental atherosclerosis has been investigated in ovariectomized mice heterozygous for the human CETP transgene and for the LDL-receptor null allele (LDLr^+/− CETP^+/−). After ovariectomy at 8 wk of age they were fed a fat/cholesterol-rich diet for 19 wk and divided into three experimental groups: dietary unmodified soy protein containing isoflavones (mg/g of diet), either at low-dose (Iso Low, 0.272, n=25), or at high-dose (Iso High, 0.535, n=28); and the atherogenic diet containing an isoflavone-depleted alcohol-washed soy protein as a control group (n=28). Aortic root lipid-stained lesion area (mean μm²×10³±SD) did not differ among Iso Low (12.3±9.9), Iso High (7.4±6.4), and controls (10.7±12.8). Autoantibody titers against plasma oxidized LDL did not differ among the experimental groups. Using the control mice as the reference value (100%), in vitro mouse peritoneal macrophage uptake of labeled acetylated LDL-cholesterol was lower in the Iso High (68%) than in the Iso Low (85%) group. The in vitro percent removal by exogenous HDL of labeled unesterified cholesterol from macrophages previously enriched with human [4-¹⁴C]-cholesteryl oleate acetylated LDL was enhanced in the Iso High group (50%). In spite of these in vitro potentially antiatherogenic actions, soy protein containing isoflavones did not modify the average size of lipid-stained area in the aortic root.     

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.     

Dietary polyunsaturated fat decreases interaction between low density lipoproteins and arterial proteoglycans

Polyunsaturated dietary fat (n−3 and n−6) results in less atherosclerosis in monkeys compared to lard (Parks, J.S., Kaduck-Sawyer, J., Bullock, B.C., and Rudel, L.L.,Arteriosclerosis 10, 1102–1112; Rudel, L.L., Parks, J.S., Johnson, F.L., and Babiak, J.,J. Lipid Res. 27, 465–474, 1986). We hypothesized that this was due, in part, to a decreased reactivity of low density lipoproteins (LDL) with arterial proteoglycans (PG). To test this hypothesis, cynomolgus monkeys were fed diets containing lard, safflower oil (n−6 polyunsaturated; Poly), menhanden fish oil (FO), or oleic acid-rich safflower oil (oleinate; Mono) for 14 mon, and plasma LDL were isolated and characterized. Several properties of LDL thought to be important in the interaction of LDL with arterial PG were measured including LDL particle size, chemical composition, sialic acid content, density distribution, apolipoprotein E (apoE) content and cholesteryl ester transition temperature. Plasma LDL cholesterol concentrations (mg/dL) after 14 mon of diet consumption averaged (mean±SEM): FO (366±45), Lard (352±27), Poly (279±24), and Mono (230±43). The composition of LDL was similar among diet groups except that FO LDL were relatively depleted of cholesteryl ester and enriched in protein and were smaller in size. LDL sialic acid content was similar among diet groups (4.5–5.0 μg/mg LDL protein). The LDL apoE/B molar ratio, a measure of the apoE content per LDL particle averaged: Mono (3.0±1.0), Poly (2.0±0.1), Lard (1.8±0.5), and FO (1.0±0.2). The FO group had a lower proportion (13%) of the apoE enriched d=1.015–1.025 g/mL subfraction of LDL than did the other diet groups (31–45%). The transition temperature of the LDL cholesteryl esters was below body temperature for the FO and Poly groups (36°C) and above for the Lard and Mono groups (40–44°C). The percentage of LDL cholesterol that formed insoluble complexes with arterial chondroitin sulfate PG averaged: Mono (29±4%), Lard (18±3%), Poly (14±3%), and FO (7±2%). Among all diet groups, there was a significant positive correlation (r=0.54) between LDL-PG complex formation and LDL apoE/B molar ratio. We conclude that dietary FO and Poly result in LDL that are less reactive with arterial PG compared to Lard or Mono fats. While FO appears to decrease PG binding by decreasing the apoE content and amount of the largest LDL subfraction, Poly fat appears to affect LDL-PG interactions by other mechanisms. Decreased LDL-PG interactions may lead to decreased atherosclerosis in animals fed polyunsaturated dietary fat.     

The effect of dietary docosahexaenoic acid on plasma lipoproteins and tissue fatty acid composition in humans

Normal, healthy male volunteers (n=6) were fed diets [high docosahexaenoic acid-DHA] containing 6 g/d of DHA for 90 d. The stabilization (low-DHA) diet contained less than 50 mg/d of DHA. A control group (n=4) remained on the low-DHA diet for the duration of the study (120 d). Blood samples were drawn on study days 30 (end of the stabilization period), 75 (midpoint of the intervention period), and 120 (end of the intervention period). Adipose tissue (AT) samples were taken on days 30 and 120. The plasma cholesterol (C), low density lipoprotein (LDL)-C and apolipoproteins (apo) [Al, B, and lipoprotein (a)] were unchanged after 90 d, but the triglycerides (TAG) were reduced from a mean value of 76.67±24.32 to 63.83±16.99 mg/dL (n=6, P<0.007 using a paired t-test) and the high density lipoprotein (HDL)-C increased from 34.83±4.38 mg/dL to 37.83±3.32 mg/dL (n=6, P<0.017 using a paired t-test). The control group showed no significant reduction in plasma TAG levels. Apo-E, however, showed a marked increase in the volunteers’ plasma after 90 d on the high-DHA diet, from 7.06±4.47 mg/dL on study day 30 to 12.01±4.96 mg/dL on study day 120 (P<0.002 using a paired t-test). The control subjects showed no significant change in the apo-E in their plasma (8.46±2.90 on day 30 vs. 8.59±2.97 on day 120). The weight percentage of plasma DHA rose from 1.83±0.22 to 8.12±0.76 after 90 d on the high-DHA diet. Although these volunteers were eating a diet free of eicosapentaenoic acid (EPA), plasma EPA levels rose from 0.38±0.05 to 3.39±0.52 (wt%) after consuming the high-DHA diet. The fatty acid composition of plasma lipid fractions—cholesterol esters, TAG, and phospholipid—showed marked similarity in the enrichment of DHA, about 10%, after the subjects consumed the high-DHA diet. The DHA content of these plasma lipid fractions varied from less than 1% (TAG) to 3.5% (phospholipids) at baseline, study day 30. EPA also increased in all plasma lipid fractions after the subjects consumed the high-DHA diet. There were no changes in the plasma DHA or EPA levels in the control group. Consumption of DHA also caused an increase in AT levels of DHA, from 0.10±0.02 to 0.31±0.07 (wt%) (n=6, P<0.001 using a paired t-test), but the amount of EPA in their AT did not change. Thus, dietary DHA will lower plasma TAG without EPA, and DHA is retroconverted to EPA in significant amounts. Dietary DHA appears to enhance apo-E synthesis in the liver. It appears that DHA can be a safe and perhaps beneficial supplement to human diets.     

Use of α-tocopherol acetate to improve fresh pig meat quality of full-fat rapeseed-fed pigs

Thirty-two pigs were allocated to one of four diets, FFRD0 and FFRD200, containing full-fat rapeseed (FFR), 150 g/kg [25–50 kg liveweight (LW)], and 250 g/kg (50–90 kg LW), or CD0 and CD200, containing equivalent quantities of rapeseed meal and 34 g/kg (25–50 kg LW) or 59.2 g/kg (50–90 kg LW) coconut oil and lard (0.5:0.5, w/w). Diets FFRD200 and CD200 were supplemented with 200 mg/kg α-tocopherol acetate (ATA). ATA supplementation significantly (P<0.001) reduced muscle drip loss. The melting point (°C) of subcutaneous fat was significantly lowered by FFR (P<0.001) but increased by ATA supplementation (P<0.05). Tissue α-tocopherol (AT) concentrations were significantly increased by ATA supplementation. Longissimus dorsi AT concentration was positively correlated with AT concentration in subcutaneous fat (r=0.86) and in plasma at 35 (r=0.65) and 77 (r=0.85) days of feeding (P<0.001). In both L. dorsi and subcutaneous adipose tissue lipids, FFRD caused a significant (P<0.001) decrease in the ratio of n-6 to n-3 fatty acids and a significant (P<0.001) increase in the ratio of polyunsaturated to saturated fatty acids. AT supplementation significantly reduced the susceptibility of L. dorsi and subcutaneous fat to lipid oxidation during storage at 4°C for up to 16 d. For all dietary treatments and storage times, lipid oxidation [mg malondialdehyde (MDA)/kg muscle] was greater in the surface layer (0–2.5 mm) of L. dorsi than below the surface (2.5–5 mm). Oxidative stability of L. dorsi lipids to iron-induced lipid peroxidation was significantly improved (P<0.001) by AT supplementation. Meat from pigs fed FFRD diets was significantly less stable to iron-induced oxidation (nmoles MDA/mg protein) at the longer incubation periods (100 and 200 min). The susceptibility of L. dorsi to iron-induced lipid oxidation decreased as the ratio of the tissue concentration of AT to unsaturated fatty acid increased.     

Long-term feeding of dietary oils alters lipid metabolism, lipid peroxidation, and antioxidant enzyme activities in a teleost (Anabas testudineus bloch)

Anabas testudineus (climbing perch), average body weight 21±1 g, were maintained in culture tanks and fed a 35% protein feed plus an additional supplementation of three dietary oils (20% each of coconut oil, palm oil, or cod liver oil). Body weight gain was similar among all groups. However, several hepatic lipogenic enzymes such as malic enzyme (ME), NADP-isocitrate dehydrogenase (ICDH), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH) and β-hydroxy-β-methyl glutaryl CoA reductase (HMG CoA reductase) were assayed, and they responded differently. Hepatic ME and G6PDH activities showed a significant decrease in the coconut oil and palm oil groups, but there was no significant change in ICDH activity. The 6PGDH activities were reduced, whereas HMG CoA reductase activity was increased in the palm oil-treated group. Cholesterol synthesis in the liver and muscle increased in the palm oil-treated group, but liver phospholipids did not show any significant change in fish supplemented with oils rich in saturated fatty acids. Triacyl-glycerol and free fatty acid concentrations were high in the coconut oil- and palm oil-supplemented groups. Lipid peroxidation products such as thiobarbituric acid-reactive substances and conjugated dienes decreased in the same two groups. Antioxidant potential was high in all groups as evidenced by increased activity of superoxide dismutase, glutathione peroxidase, and glutathione content. The results of this study indicate that in fish, dietary lipids depress hepatic lipogenic activity as well as lipid peroxidation products by maintaining high levels of antioxidant enzymes.     

Species variation in the atherogenic profile of monkeys: Relationship between dietary fats,lipoproteins, and platelet aggregation

Because lipoproteins and platelet aggregation have been implicated in atherogenesis, relative differences in the response of these variables to dietary fat saturation were compared in three species of monkeys differing in their susceptibility to atherosclerosis (cebus, rhesus, and squirrel monkeys). Both long-term (8–12 years) and short-term (8 weeks) responses to diets containing 31% fat calories were examined in the same monkeys. As expected, long-term feeding of coconut oil by comparison to corn oil produced significantly higher plasma concentrations of total cholesterol, LDL cholesterol, apoB, and triglycerides, as well as higher ratios of LDL/HDL cholesterol and apo B/apo A-I. These responses were characteristic of all species with cebus being most responsive and rhesus the least. The shortterm plasma cholesterol response to animal fats (butter, lard, beef tallow) was significantly less than that to coconut oil. When fish oil was substituted for two-thirds of either corn oil or coconut oil, exceptional decreases occurred in plasma cholesterol and triglycerides, as well as in HDL cholesterol and apo A-I concentrations despite the fact that the fish oil diets contained more saturated fat and less polyenes than the corn oil diet. Platelet aggregation tended to increase with saturated fat consumption and greatly decreased with fish oil intake in all monkeys, although cebus monkeys were ten-fold more resistant to platelet aggregation than the other two species. The molecular species of platelet phosphatidylcholine (PC) varied with both the dietary fat fed and species of monkey. An inverse correlation (r=−0.60; p<0.001) was found between changes in one such PC molecular species (18∶0−20∶4) induced by diet and the platelet aggregation threshold. These results demonstrate that the lipemic and platelet responses to dietary saturated fat depend upon both the type of fat (i.e., the specific combination of dietary fatty acids, including the chain length of saturated fatty acids and the degree of polyunsaturation) and the species of monkey (genetic component) in which the response is elicited.     

Vitamin E supplementation increases circulating vitamin E metabolites tenfold in end-stage renal disease patients

Vitamin E supplementation could elevate circulating vitamin E metabolites while modulating oxidative and inflammatory status in end-stage renal failure patients undergoing hemodialysis. Plasma concentrations of carboxyethyl-hydroxychromanols (α-and γ-CEHC), ascorbic acid, α-and γ-tocopherols, E₂-isoprostanes, and inflammatory biomarkers [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), ferritin, and C-reactive protein (CRP)] were measured in blood samples obtained from patients (n=11) before and after dialysis on two occasions prior to, and at 1 and 2 mon of daily vitamin E supplementation (400 IU RRR-α-tocopherol). Supplementation nearly doubled plasma α-tocopherol concentrations (from 18±0.5 to 31±1.7 μM, P<0.0001), whereas γ-tocopherol concentrations decreased (from 2.8±0.3 to 1.7±0.2 μM, P=0.001). Serum α-CEHC increased 10-fold from 68±3 to 771±175 nM (P<0.0001), and γ-CEHC increased from 837±164 to 1136±230 nM (P=0.008). Vitamin E supplementation also increased postdialysis hematocrits from 38±1% to 41±1% (P<0.001). Dietary antioxidant intakes (vitamins E and C) were low in most subjects; plasma ascorbic acid levels (88±27 μM) decreased significantly with dialysis (33±11 μM, P=0.01). Plasma Il-6, CRP, TNF-α, and free F₂-isoprostane concentrations were elevated throughout the study. There is a complex relationship between chronic inflammation and oxidative stress that is not mitigated by short-term vitamin E supplementation. Importantly, serum vitamin E metabolite concentrations that increased 10-fold within 30 d of supplementation did not increase further, suggesting routes other than urine for removal of metabolites.     

Plasma kinetics of free and esterified cholesterol in familial hypercholesterolemia: Effects of simvastatin

The objective of this study was to evaluate the kinetics of both free and esterified forms of cholesterol contained in a emulsion that binds to LDL receptors (LDE) in subjects with heterozygous familial hypercholesterolemia (FH), and the same subjects under the effects of high-dose simvastatin treatment, as compared with a control normolipidemic group (NL). Twentyone FH patients (44.0±13.0 yr, 12 females, LDL cholesterol levels 6.93±1.60 mmol/L) and 22 normolipidemic patients (44.0±15.0, 10 females, LDL cholesterol levels 3.15±0.62 mmol/L) were injected intravenously with ¹⁴C-cholesteryl ester and ³H-cholesterol. FH patients were also evaluated after 2 mon of 40 or 80 mg/d simvastatin treatment, and plasma samples were collected over 24 h to determine the residence time (RT, in h) of both LDE labels, expressed as the median (25%; 75%). The RT of both ¹⁴C-cholesteryl ester and ³H-cholesterol were greater in FH than in NL [FH: 36.0 (20.5; 1191.0), NL: 17.0 (12.0–62.5), P=0.015; and FH: 52.0 (30.0; 1515.0); NL 20.5 (14.0–30.0) P<0.0001]. Treatment reduced LDL cholesterol by 36% (P<0.0001), RT of ¹⁴C-cholesteryl ester by 49% (P=0.0029 vs. baseline), and ³H-cholesterol RT by 44% (P=0.019 vs. baseline). After treatment, the RT values of ¹⁴C-cholesteryl ester in the FH group approached the NL values (P=0.58), but the RT of ³H-cholesterol was still greater than those for the NL group (P=0.01). The removal of LDE cholesteryl esters and free cholesterol was delayed in FH patients. Treatment with a high dose of simvastatin normalized the removal of cholesterol esters but not the removal of free cholesterol.     

Postpartum Weight Retention is Associated with Elevated Ratio of Oxidized LDL Lipids to HDL-Cholesterol

Oxidized LDL lipids (ox‐LDL) are associated with lifestyle diseases such as cardiovascular diseases, metabolic syndrome and type 2 diabetes. The present study investigated how postpartum weight retention effects on ox‐LDL and serum lipids. The study is a nested comparative research of a cluster‐randomized controlled trial, NELLI (lifestyle and counselling during pregnancy). During early pregnancy (8–12 weeks) and 1 year postpartum, 141 women participated in measurements for determining of plasma lipids: total cholesterol (T‐C), LDL‐cholesterol (LDL‐C), HDL‐cholesterol (HDL‐C), triacylglycerols (TAG) and ox‐LDL. Subjects were stratified into tertiles (weight loss, unaltered weight and weight gain groups) based on their weight change from baseline to follow‐up. Ox‐LDL was determined by baseline level of conjugated dienes in LDL lipids. Among the group of weight gainers, concentration of TAG reduced less (?0.14 vs. ?0.33, p = 0.002), HDL‐C reduced more (?0.31 vs. ?0.16, p = 0.003) and ox‐LDL/HDL‐C ratio increased (3.0 vs. ?0.2, p = 0.003) when compared to group of weight loss. Both T‐C and LDL‐C elevated more (0.14 vs. ?0.21, p = 0.008; 0.31 vs. 0.07, p = 0.015) and TAG and ox‐LDL reduced less (?0.33 vs. 0.20, p = 0.033; ?3.33 vs. ?0.68, p = 0.026) in unaltered weight group compared to weight loss group. The women who gained weight developed higher TAG and ox‐LDL/HDL‐C ratio as compared to those who lost weight. Postpartum weight retention of 3.4 kg or more is associated with atherogenic lipid profile.     

Postprandial and short-term effects of dietary virgin olive oil on oxidant/antioxidant status

It is generally believed that virgin olive oil consumption has beneficial effects, but little is known about its effects postprandially on oxidant/antioxidant status. The aim of this study was to determine changes in oxidative stress biomarkers and lipid profile after a single dose of virgin olive oil and after 1 wk of daily consumption. Sixteen subjects (9 men, 7 women) ingested 50 mL of virgin olive oil in a single dose. Blood samples were collected from 0 to 24 h. Thereafter, 14 participants (8 men, 6 women) followed a 1-wk 25 mg/d virgin olive oil dietary intervention. Blood samples were collected at the end of this period. Serum TAG (P=0.016), plasma FA (P<0.001) and lipid peroxidation products in plasma (P<0.001) and VLDL (P=0.007) increased, reaching a peak at 4–6 h, and returning to baseline values at 24 h after oil ingestion. The opposite changes were observed in plasma glutathione peroxidase (P=0.001) and glutathione reductase (GR) (P=0.042). No changes in LDL lipid peroxidation or resistance to oxidation were observed postprandially. At 24 h, plasma oleic acid remained increased (P<0.05) and resistance of LDL to oxidation improved (P<0.05). After 1 wk of virgin olive oil consumption, plasma oleic acid (P=0.031), resistance of LDL to oxidation (P<0.05), and plasma GR activity (P=0.005) increased. These results indicate that changes in oxidant/antioxidant status occur after oral virgin olive oil. Virgin olive oil consumption could provide short-term benefits for LDL resistance to oxidation and in glutathione-related enzyme activities.     

Eicosapentaenoic acid is primarily responsible for hypotriglyceridemic effect of fish oil in humans

The aim of this study was to determine whether eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), or both, were responsible for the triglyceride (TG)-lowering effects of fish oil. EPA (91% pure) and DHA (83% pure), a fish oil concentrate (FOC; 41% EPA and 23% DHA) and an olive oil (OO) placebo (all ethyl esters) were tested. A total of 49 normolipidemic subjects participated. Each subject was given placebo for 2–3 wk and one of the n-3 supplements for 3 wk in randomized, blinded trials. The target n-3 fatty acid (FA) intake was 3 g/day in all studies. Blood samples were drawn twice at the end of each supplementation phase and analyzed for lipids, lipoproteins, and phospholipid FA composition. In all groups, the phospholipid FA composition changed to reflect the n-3 FA given. On DHA supplementation, EPA levels increased to a small but significant extent, suggesting that some retroconversion may have occurred. EPA supplementation did not raise DHA levels, however, FOC and EPA produced significant decreases in both TG and very low density lipoprotein (VLDL) cholesterol (C) levels (P<0.01) and increases in low density lipoprotein (LDL) cholesterol levels (P<0.05). DHA supplementation did not affect cholesterol, triglyceride, VLDL, LDL, or high density lipoprotein (HDL) levels, but it did cause a significant increase in the HDL₂/HDL₃ cholesterol ratio. We conclude that EPA appears to be primarily responsible for TG-lowering (and LDL-C raising) effects of fish oil.     

Effect of low-to-moderate amounts of dietary fish oil on neutrophil lipid composition and function

Although essential to host defense, neutrophils are also involved in numerous inflammatory disorders including rheumatoid arthritis. Dietary supplementation with relatively large amounts of fish oil [containing >2.6 g eicosapentaenoic acid (EPA) plus 1.4 g docosahexaenoic acid (DHA) per day] can attenuate neutrophil functions such as chemotaxis and superoxide radical production. In this study, the effects of more moderate supplementation with fish oil on neutrophil lipid composition and function were investigated. The rationale for using lower supplementary doses of fish oil was to avoid adverse gastrointestinal problems, which have been observed at high supplementary concentrations of fish oil. Healthy male volunteers aged <40 yr were randomly assigned to consume one of six dietary supplements daily for 12 wk (n=8 per treatment group). The dietary supplements included four different concentrations of fish oil (the most concentrated fish oil provided 0.58 g EPA plus 1.67 g DHA per day), linseed oil, and a placebo oil. The percentages of EPA and DHA increased (both P<0.05) in neutrophil phospholipids in a dose-dependent manner after 4 wk of supplementation with the three most concentrated fish oil supplements. No further increases in EPA or DHA levels were observed after 4 wk. The percentage of arachidonic acid in neutrophil phospholipids decreased (P<0.05) after 12 wk supplementation with the linseed oil supplement or the two most concentrated fish oil supplements. There were no significant changes in N-formyl-met-leu-phe-induced chemotaxis and superoxide radical production following the dietary supplementations. In conclusion, low-to-moderate amounts of dietary fish oil can be used to manipulate neutrophil fatty acid composition. However, this may not be accompanied by modulation of neutrophil functions such as chemotaxis and superoxide radical production.     

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.