Cholestyramine alters the lipid and energy metabolism of chicks fed dietary medium-or long-chain triacylglycerol

The effects of cholestyramine, a bile acid binding polymer, on the lipid and energy metabolism of chicks given dietary medium-chain triacylglycerol (MCT) or long-chain triacylglycerol (LCT) were investigated. Chicks (from 8 to 17 days of age) were fed diets containing MCT or LCT at 200 g oil/kg diet with or without 2% cholestyramine under equalized feeding conditions. An adjusted LCT diet was formulated in order to supply another group with daily nutrients and dietary metabolizable energy (ME) equal to MCT groups, except for corn starch. ME intakes of chicks given MCT or LCT diets were reduced by cholestyramine; consequently, fat and energy retention was reduced, though the reduction was more drastic in chicks fed LCT. This was caused by a change in amounts of the fecal excretion of fat and bile acids. Cholestyramine enhanced the excretion of octanoic acid (8∶0) in the feces, which suggests that bile acids are needed for 8∶0 absorption. Cholestyramine affects the utilization of dietary MCT and LCT by lowering fat and energy retention in chicks. However, the effect of cholestyramine on MCT utilization was smaller than its effect on utilization of LCT.     

Modulation of apolipoprotein E-mediated plasma clearance and cell uptake of emulsion particles by cholesteryl ester

Cholesteryl ester, along with triglyceride (TG), is the major core component of plasma lipoproteins. We investigated the effect of core composition on the physical state and metabolic behavior of lipid emulsions, as model particles of lipoproteins. Fluorescence studies using 1,6-diphenylhexatriene analogs showed that although cholesteryl oleate (CO) significantly decreased core mobility, the surface rigidity of phosphatidylcholine (PC) monolayers was independent of core composition. When intravenously injected into rats, the increased amount of core CO tended to retard TG emulsion removal from plasma, and the initial clearance rate was correlated with the amount of apolipoprotein E (apoE) bound from plasma. In addition, PC liposomes with a similar emulsion particle size showed negligible binding of apoE and were cleared at a slower rate compared to all emulsions. Furthermore, the effect of CO on the binding behavior of apoE to the emulsion surface and the emulsion uptake by hepatocytes was assessed in vitro. Replacing core TG with CO was found to decrease the apoE binding capacity to emulsions markedly without changing the binding affinity and thereby to reduce the cell uptake of emulsion particles by HepG2 cells. These results indicate that the physical state of core lipids, which can be modulated by cO content, plays a role in emulsion metabolism through the alteration in apoE binding.     

Lymphatic transport of a physical mixture of medium-and long-chain TAG in rats

Lymphatic transport of a mixture of medium-chain TAG (MCT) and long-chain TAG (LCT) was studied in lymph-cannulated rats. Animals were administered a test emulsion containing either triolein, tricaprylin, or a 1∶1 mixture of triolein and tricaprylin, and the lymph was collected for 24 h. The lymphatic recovery rate of medium-chain FA (MCFA) was significantly higher in rats given the TAG mixture than in those given MCT alone. The lymphatic recovery rate of long-chain FA (LCFA) also was significantly higher in rats given the TAG mixture than in those given LCT alone. No TAG containing three MCFA (i.e., MCT) was detected, and 37.7% of TAG containing one or two MCFA was detected in the lymph TAG when rats were given the TAG mixture. These results indicate that lymphatic transport of MCFA and LCFA can be modified by the combination of MCT and LCT.     

LDL binding to lipid emulsion particles: effects of incubation duration,temperature, and addition of plasma subfractions

Lipid emulsions used in parenteral nutrition interact with lipoproteins leading to exchanges of lipids and acquisition of several apolipoproteins (apo). It has been previously observed that, during in vitro incubation of emulsions with purified LDL, a variable fraction of LDL binds to TG-rich emulsion particles. The purpose of this study was to better characterize such an interaction. Two emulsions containing 20% soybean oil (Endolipid, B. Braun AG, Melsungen, Germany) or fish oil were incubated with LDL, either alone or in the presence of various plasma subfractions, for different durations and at different temperatures. The fraction named M-LE (containing TG-rich particles modified after incubation) was separated by ultracentrifugation or gel filtration chromatography, and the apoB content was measured as an index of LDL binding to TG-rich emulsion particles. The formation of such complexes was visualized by freeze-fracture electron microscopy. LDL binding was not influenced by the method used for M-LE isolation. Binding occurred quickly, did not increase with prolonged incubation, was inversely related to increasing incubation or ultracentrifugation temperature, and withstood 40 h of ultracentrifugation at 163,000 x g. The presence of glycerol or excess phospholipids in the emulsion did not markedly affect the formation of the complexes. In contrast, adding very small amounts of lipoprotein-poor plasma (d > 1.210 g/mL) or HDL markedly reduced the process, and albumin had no effect. The TG composition of the emulsion influenced the binding of LDL to TG-rich particles, since more apoB was found in M-LE from fish oil than from soybean oil emulsion.     

Interactions between medium-chain and long-chain triacylglycerols in lipid and energy metabolism in growing chicks

The combined effects of dietary medium-chain triacylglycerols (MCT) and long-chain triacylglycerols (LCT) on lipid and energy utilization in chicks were investigated. Corn oil was used as the LCT source, and trioctanoin (8∶0) was used as the MCT source. The efficiency of dietary energy utilization (such as metabolizable energy values and fat and energy retention) decreased linearly as the level of MCT increased, but the efficiency of dietary protein utilization (protein retained per protein consumed) was not affected in a consistent manner. Fecal saturated and monounsaturated fatty acid composition was dependent on the dietary fatty acid composition, whereas fecal linoleic acid content was not. It is concluded that dietary MCT and LCT influence each other to some degree, with respect to protein and lipid metabolism in chicks. Moreover, in most cases, the nutritional characteristics of each triacylglycerol, including food efficiency and fat and energy retention, are independent of each other in growing chicks.     

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.     

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.     

Enteral feeding a structured lipid emulsion containing fish oil prevents the fatty liver of sepsis

Fish oils (FO) have been shown to reduce plasma triglycerides (TG). In this study we evaluated whether enteral feeding with a structured lipid emulsion (SLE) containing FO and medium-chain triglycerides (MCT) would prevent the hypertriglyceridemia and fatty infiltration of the liver that develops during sepsis. For five days, male Lewis rats (275–300 g) were fed intragastrically a nutritionally complete diet containing a SLE or a similar diet with a soybean oil emulsion (SOE) in place of the SLE. On the fifth day, sepsis was induced by intravenously injecting 8×10⁷ liveEscherichia coli colonies/100 g b.w.; 24 h later the control SLE, septic SLE, control SOE, and septic SOE rats were sacrificed. Diet, but not treatment, had a significant effect on serum TG and free fatty acids (FFA). Feeding the SLE reduced the plasma FFA of the control and septic rats by more than 50% in comparison to both control and septic rats fed the SOE. Soleus muscle activity of lipoprotein lipase from the septic SLE rats was 44% higher than the control SLE rats. Soleus muscle from the septic SLE rats also had a twofold greater activity of lipoprotein lipase than the septic SOE rats. TG did not accumulate in the livers of the septic rats fed SLE when compared to the control SLE rats and the rats fed the SOE. Livers from the septic rats fed the SLE had a third of the TG that were present in the livers from the septic rats fed the SOE. The rate of incorporation of [¹⁴C]oleate into liver lipids was significantly lower in septic rats fed SLE than in those fed the SOE. TG esterification was 70% lower in the septic rats fed SLE rather than the SOE. Our findings suggest that the SLE with FO and MCT has a role in the prevention of the sepsis-associated fatty liver by reducing the biosynthesis of liver TG.     

Major clofibrate effects on liver and plasma lipids are independent of changes in polyunsaturated fatty acid composition induced by dietary fat

The effects of clofibrate on the content and composition of liver and plasma lipids were studied in mice fed for 4 wk on diets enriched in n−6 or n−3 polyunsaturated fatty acids (PUFA) from sunflower oil (SO) or fish oil (FO), respectively; both oils were fed at 9% of the diet (dry weight basis). Only FO was hypolipidemic. Both oil regimes led to slightly increased concentrations of phospholipids (PL) and triacylglycerols (TG) in liver as compared with a standard chow diet containing 2% fat. Clofibrate promoted hypolipidemia only in animals fed SO. Its main effect was to enlarge the liver, such growth increasing the amounts of major glycerophospholipids while depleting the TG. SO and FO consumption changed the proportion of n−6 or n−3 PUFA in liver and plasma lipids in opposite ways. After clofibrate action, the PUFA of liver PL were preserved better than in the absence of oil supplementation. However, most of the drug-induced changes (e.g., increased 18∶1n−9 and 20∶3n−6, decreased 22∶6/20∶5 ratios) occurred inrrespective of lipids being rich in n−6 or n−3 PUFA. The concentration of sphingomyelin (SM), a minor liver lipid that virtually lacks PUFA, increased with the dietary oils, decreased with clofibrate, and changed its fatty acid composition in both situations. Thus. oil-increased SM had more 22∶0 and 24∶0 than clofibrate-decreased SM, which was significantly richer in 22∶1 and 24∶1.     

Eicosenoic and docosenoic acid incorporation in serum lipoproteins in rats fed rapeseed oil

Rats were fed rapeseed oil rich in eicosenoic (20∶1) and docosenoic (22∶1) acids for 7 days, and the fatty acid composition of the lipid classes of serum and serum lipoproteins was determined. Concentrations of 20∶1 and 22∶1 acids in the lipid classes were variable, especially among lipoproteins, and were a direct function of the alimentary state of the animal. The results suggest differences in the incorporation of the above acids among the major lipoprotein types and various lipid classes within a given lipoprotein type. The quick partial disappearance of very low density lipoproteins (VLDL) and of low density lipoproteins (LDL) containing 20∶1 and 22∶1 acids upon starvation and the preferential incorporation of these acids in the triacylglycerols of high density lipoproteins (HDL) are discussed.     

Olive Oil-Based Lipid Emulsions Do Not Influence Platelet Receptor Expression in Comparison to Medium and Long Chain Triglycerides In vitro

Lipid emulsions influence platelet aggregation and receptor expression. However, the effect on platelet function is not fully explained. Therefore, the aim of this study was to examine the influence of the lipids Lipofundin^®, Lipidem^® and ClinOleic^® on surface expressions of P‐selectin, GPIb and GPIIb/IIIa on platelets in vitro. Whole blood was incubated in two different concentrations (0.06 and 0.6 mg/ml) of LCT/MCT, n‐3/LCT/MCT and LCT‐MUFA for 30 min, followed by activation with TRAP‐6 or ADP for flow‐cytometric assay. Rates of P‐selectin, GPIb and GPIIb/IIIa expression were analyzed. There was a significant increase in GPIIb/IIIa‐ and P‐selectin‐expression after incubation with LCT/MCT and n‐3/LCT/MCT at the concentration of 0.6 mg/ml, without and after stimulation with TRAP‐6 and ADP. GPIb was significantly decreased. Accordingly, LCT‐MUFA had no effect on receptor expression of platelets in vitro. We demonstrated that LCT‐MUFA did not activate receptor expression of platelets whereas LCT/MCT significantly increased platelet aggregation in vitro. This finding should be noted for parenteral nutrition of intensive care patients and, in the future, might provide further insight into the pathogenic pathways of acute thromboembolic events. However, prospectively designed clinical studies are needed to support our results.     

Effects of a (n−3) polyunsaturated fatty acid-deficient diet on profiles of serum vitellogenin and lipoprotein in vitellogenic trout (Salmo gairdneri)

During the 6 months of vitellogenesis, 3-year-old female trout (Salmo gairdneri) were fed either an enriched (E) or an (n−3) polyunsaturated fatty acid (PUFA)-deficient (D) diet; serum vitellogenin (VG) and lipoproteins (d<1.21 g/ml) were analyzed at the third month of vitellogenesis (September) and at ovulation (December). The serum content of high density lipoproteins (HDL), the major protein class, maintained a mean value of 1500 mg/dl at both stages and with both diets. On the contrary, very low density lipoproteins (VLDL) were 90% higher during vitellogenesis than at spawning time, whereas excess vitellogenin circulated at this period (6580 mg/dl serum with diet E). The diet deficient in (n−3) lowered serum vitellogenin content by 16% in September and by 26% in December. The degree of (n−3) PUFA incorporation moderately decreased in low density lipoproteins (LDL) and in HDL with the (n−3)-deficient diet. The effect was more pronounced for 20∶5. On the other hand, essential 22∶6 was incorporated into vitellogenin at the same rate in September as in December with diet E (23% and 25%, respectively), whereas after a 3-month deficiency, the percentage fell to 12%; this percentage rose again to 19% at spawning time. These findings show that, although stored (n−3) PUFA were not exhausted after a 6-month dietary deficiency, the incorporation of essential fatty acids (EFA) into vitellogenin during the early stages of oogenesis was low, suggesting changes in egg composition that may influence hatching.     

A comparison of the effect of medium- vs. long-chain triglycerides on the <Emphasis Type="Italic">in vitro</Emphasis> solubilization of cholesterol and/or phytosterol into mixed micelles

Despite clinical evidence of the cholesterol-lowering effects of phytosterols, the exact mechanisms involved are still unclear. Displacement of cholesterol by phytosterols from mixed micelles, which is due to their greater hydrophobicity, is one of the hypotheses for the lumenal effects contributing to the reduction of intestinal cholesterol absorption. In this study a dynamic in vitro lipolysis method was used to examine the solubilization behavior of cholesterol and/or phytosterols during lipolysis to probe the efficacy of cholesterol displacement from mixed micelles by phytosterols. The effects of lipid chain length on sterol solubilization were studied by using microcrystalline suspensions containing 17% phytosterol or cholesterol, formulated in long-chain TG (LCT) and medium-chain TG (MCT). When digesting cholesterol suspended in LCT, the entire cholesterol dose was incorporated into the micellar phase. For the cholesterol formulation suspended in MCT, 50.3% of the initial dose was recovered in the micelles. Under the respective conditions, we observed lower solubilization of phytosterols than of cholesterol (roughly fourfold). Only 25% of the initial phytosterol dose was solubilized from suspensions formulated with LCT, and 13% was solubilized from MCT formulations. Co-administration of phytosterol and cholesterol suspensions showed a significant reduction of cholesterol solubilization, particularly when dosed in MCT, with ≈25% of the cholesterol dose solubilized. Insignificant amounts of cholesterol were displaced by phytosterols when cholesterol was presolubilized in the mixed micelles. The results show that, compared with LCT, mixed micelles containing MCT lipolysis products have a reduced solubilizing capacity for cholesterol, which adds to the effectiveness of the phytosterols in displacing cholesterol. This suggests potential benefits of using medium chain length lipids in cholesterol-lowering phytosterol products.     

Vitamin E Transfer from Lipid Emulsions to Plasma Lipoproteins: Mediation by Multiple Mechanisms

The present study determined alpha-tocopherol mass transfer from an alpha-tocopherol-rich emulsion to LDL and HDL, and assessed the potential of different mechanisms to modulate alpha-tocopherol transfers. Emulsion particles rich in alpha-tocopherol were incubated in vitro with physiological concentrations of LDL or HDL. The influence of plasma proteins was assessed by adding human lipoprotein poor plasma (LPP) fraction with intact vs heat inactivated PLTP, or with a specific cholesteryl ester transfer protein (CETP) inhibitor, or by adding purified PLTP or pig LPP which lacks CETP activity. After 4 h incubation in absence of LPP, alpha-tocopherol content was increased by ~80% in LDL and ~160% in HDL. Addition of LPP markedly enhanced alpha-tocopherol transfer leading to 350–400% enrichment in LDL or HDL at 4 h. Higher (~10 fold) enrichment was achieved after 20 h incubation with LPP. Facilitation of alpha-tocopherol transfer was (i) more than 50% higher with human vs pig LPP (despite similar PLTP phospholipid transfer activity), (ii) reduced by specific CETP activity inhibition, (iii) not fully suppressed by heat inactivation, and (iv) not restored by purified PLTP. In conclusion, alpha-tocopherol content in LDL and HDL can be markedly raised by rapid transfer from an alpha-tocopherol-rich emulsion. Our results indicate that alpha-tocopherol mass transfer between emulsion particles and lipoproteins is mediated by more than one single mechanism and that this transfer may be facilitated not only by PLTP but likely also by other plasma proteins such as CETP.     

Tripalmitin–Sodium Dodecyl Sulfate Emulsion Droplet Liquid vs. Solid State Impacts in vitro Digestive Lipolysis

Questions remain as to the impact of lipid structure, including crystallinity, on digestibility and metabolic response. This study was undertaken to determine the impact of triacylglycerol crystallinity on digestibility using undercooled (liquid emulsion, LE) and crystalline (solid emulsion, SE) particles exposed to an in vitro model simulating upper gastrointestinal tract (GIT) digestive conditions. By hot microfluidization, 10 wt% tripalmitin oil‐in‐water emulsions (D_3,2 ~ 0.115 nm) with 0.9 wt% sodium dodecyl sulfate (SDS) were prepared. SE demonstrated complex melting behavior, was predominantly in the beta polymorph, and consisted of a heterogeneous mixture of anisometric particles. In vitro duodenal lipolysis was more extensive for the spherically shaped LE droplets vs. SE (P < 0.05), despite the fact that exposure to simulated gastric conditions (at pH 2, but not at pH 7) induced partial crystallization. Therefore, lipid droplet physical state impacted and was impacted by exposure to gastrointestinal conditions, with differences observed in fatty acid digestive release and implications for lipid absorption.     

Replacement of dietary fish oil with increasing levels of linseed oil: Modification of flesh fatty acid compositions in Atlantic salmon (<Emphasis Type="Italic">Salmo salar</Emphasis>) using a fish oil finishing diet

Five groups of salmon, of initial mean weight 127±3 g, were fed increasing levels of dietary linseed oil (LO) in a regression design. The control diet contained capelin oil (FO) only, and the same oil was blended with LO to provide the experimental diets. After an initial period of 40 wk, all groups were switched to a finishing diet containing only FO for a further 24 wk. Growth and flesh lipid contents were not affected by dietary treatment. The FA compositions of flesh total lipids were linearly correlated with dietary FA compositions (r ²=0.88–1.00, P<0.0001). LO included at 50% of added dietary lipids reduced flesh DHA and EPA (20∶5n−3) concentrations to 65 and 58%, respectively, of the concentrations in fish fed FO. Feeding 100% LO reduced flesh DHA and EPA concentrations to 38 and 30%, respectively, of the values in fish fed FO. Differences between diet and flesh FA concentrations showed that 16∶0, 18∶1n−9, and especially DHA were preferentially retained in flesh, whereas 18∶2n−6, 18∶3n−3, and 22∶1n−11 were selected against and presumably utilized for energy. In fish previously fed 50 and 100% LO, feeding a finishing diet containing FO for 16 wk restored flesh DHA and EPA concentrations, to ≈80% of the values in fish fed FO throughout. Flesh DHA and EPA concentrations in fish fed up to 50% LO were above recommended intake values for humans for these EFA. This study suggests that LO can be used as a substitute for FO in seawater salmon feeds and that any reductions in DHA and EPA can be largely overcome with a finishing diethigh in FO before harvest.     

Lipid Emulsions Differentially Affect LPS-Induced Acute Monocytes Inflammation: In Vitro Effects on Membrane Remodeling and Cell Viability

The aim of this study was to assess how lipid emulsions for parenteral nutrition affect lipopolysaccharide (LPS)‐induced acute monocyte inflammation in vitro. An 18 h long LPS induced human monocyte leukemia cell stimulation was performed and the cell‐growth medium was supplemented with three different industrial lipid emulsions: Intralipid^®, containing long‐chain triglycerides (LCT—soybean oil); Medialipid^®, containing LCT (soybean oil) and medium‐chain triglycerides (MCT—coconut oil); and SMOFlipid^®, containing LCT, MCT, omega‐9 and ‐3 (soybean, coconut, olive and fish oils). Cell viability and apoptosis were assessed by Trypan blue exclusion and flow cytometry respectively. Monocyte composition and membrane remodeling were studied using gas chromatography and NR12S staining. Microparticles released in supernatant were measured by prothrombinase assay. After LPS challenge, both cellular necrosis and apoptosis were increased (threefold and twofold respectively) and microparticle release was enhanced (sevenfold) after supplementation with Medialipid^® compared to Intralipid^®, SMOFlipid^® and monocytes in the standard medium. The monocytes differentially incorporated fatty acids after lipid emulsion challenge. Finally, lipid‐treated cells displayed microparticles characterized by disrupted membrane lipid order, reflecting lipid remodeling of the parental cell plasma membrane. Our data suggest that lipid emulsions differentially alter cell viability, monocyte composition and thereby microparticle release. While MCT have deleterious effects, we have shown that parenteral nutrition emulsion containing LCT or LCT and MCT associated to n‐3 and n‐9 fatty acids have no effect on endotoxin‐induced cell death and inflammation.     

Effects of n−3 and n−6 fatty acids on the activities and expression of hepatic antioxidant enzymes in autoimmune-prone NZB×NZW F1 mice

Menhaden fish oil (FO) containing n−3 fatty acids dramatically extends the life span and delays the onset and progression of autoimmune disease in (NZB×NZW)F₁ (B/W) female mice as compared to those fed corn oil (CO) rich in n−6 lipids. As an inefficient antioxidant defense system has been linked to autoimmune diseases, the present study was undertaken to determine whether the protective action of n−3 lipids is mediated through their antioxidant defense system. Weanling B/W mice were fed a nutritionally adequate, semipurified diet containing CO or krill oil (KO) or FO at 10% level (w/w)ad libitum until the mice were 6.5 months old. All diets contained the same level of vitamin E (21.5 mg/100 g diet). We compared the effects of feeding n−6 and n−3 lipids on survival, kidney disease, hepatic microsomal lipid composition, peroxidation, and on the activity and mRNA expression of the antioxidant enzymes catalase, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in 6.5-month-old B/W mice. The results showed that when compared to livers from CO-fed mice, livers from KO- and FO-fed mice showed: (i) significantly higher (P<0.001) activities and expression of CAT, GSH-Px and SOD; (ii) significantly lower (P<0.001) arachidonic acid (20∶4n−6) and linoleic acid (18∶2n−6) and higher (P<0.001) eicosapentaenoic acid (20∶5n−3) and docosahexaenoic acid (22∶6n−3) levels in hepatic microsomes; and (iii) significantly lower (P<0.001) estimated peroxidation indices and thiobarbituric acid reactive substances generation. The data indicate that one of the mechanisms through which the n−3 lipids delay the onset of autoimmune diseases in B/W mice may be through maintenance of higher activities and expression of hepatic antioxidant enzymes.     

Lymphatic absorption of structured glycerolipids containing medium-chain fatty acids and linoleic acid,and their effect on cholesterol absorption in rats

The effects of various structured triglycerides containing medium-chain (caprylic or capric acids) and long-chain (linoleic acid) fatty acids on fatty acid and cholesterol absorption were studied in lymph-cannulated rats. A considerable portion of capric and caprylic acid was absorbed through the lymph duct, although to a lesser extent than was linoleic acid. Capric and linoleic acid located at the 2-position of 2-decanoyl-1,3-dilinoleoyl-glycerol (18∶2/10∶0/18∶2) and 2-linoleoyl-1,3-didecanoyl-glycerol (10∶0/18∶2/10∶0), respectively, tended to be absorbed more efficiently than those located at the 1- and 3-position or those from tricaprin (10∶0/10∶0/10∶0) or trilinolein (18∶2/18∶2/18∶2). A similar trend was observed when the medium-chain fatty acid was caprylic acid instead of capric acid. Caprylic acid absorption from 2-octanoyl-1,3-dilinoleoylglycerol (18∶2/8∶0/18∶2) was significantly greater (p<0.05) than from 2-linoleoyl-1,3-dioctanoyl-glycerol (8∶0/18∶2/8∶0) or tricaprylin (8∶0/8∶0/8∶0). Preferential absorption of caprylic and linoleic acid was not observed when the 1 to 2 and the 2 to 1 mixtures of 8∶0/8∶0/8∶0 and 18∶2/18∶2/18∶2, respectively, were administered. The structured lipids did not affect the lymphatic absorption of cholesterol. The results suggest that structured triglycerides composed of medium-chain fatty acids and linoleic acid may be more useful for the treatment of lipid malabsorption than are mixtures of medium-chain triglyceride (MCT) and long-chain triglycride (LCT).     

Modulation of renal injury in pcy mice by dietary fat containing n−3 fatty acids depends on the level and type of fat

Low-fat diets and diets containing n−3 fatty acids (FA) slow the progression of renal injury in the male Han:Sprague-Dawley (SPRD)-cy rat model of polycystic kidney disease. To determine whether these dietary fat effects are similar in females and in another model of renal cystic disease, in this study we used both male and female pcy mice to examine the effects of fat level and type on disease progression. Adult pcy mice were fed 4, 10, or 20 g soybean oil/100 g diet for 130 d in study 1. In study 2, weanling pcy mice were fed high or low levels of fat rich in 18∶2n−6 (corn oil, CO) 18∶3n−3 (flaxseed oil/CO 4∶1 g/g, FO), or 22∶6n−3 (algal oil/CO 4∶1 g/g, DO) for 8 wk. In adult pcy mice, low-compared with high-fat diets lowered kidney weights (2.4±0.2 vs. 3.1±0.2 g/100 g body weight, P=0.006) and serum urea nitrogen (SUN) (9.6±0.6 vs. 11.9±0.6 mmol/L, P=0.009), whereas in young pcy mice it reduced renal fibrosis volumes (0.44±0.04 vs. 0.62±0.04 mL/kg body weight, P<0.0001). FO feeding in young pcy mice mitigated the detrimental effects of high fat on fibrosis while not altering kidney size, function, and oxidative damage when compared with the CO-fed mice. In contrast, DO-compared with CO-fed mice had higher kidney weights (2.64±0.07 vs. 2.24±0.08 g/100 g body weight, P=0.005), SUN (9.4±0.57 vs. 7.0±0.62 nmol/L, P<0.0001), and cyst volumes (7.9±0.28 vs. 6.2±0.30 mL/kg body weight, P<0.0001) and similar levels of oxidative damage and fibrosis. The FA compositions of the diets were reflected in the kidneys: 18∶2n−6, 18∶3n−3, and 22∶6n−3 were the highest in the CO, FO, and DO diets, respectively. Dietary effects on kidney disease progression were similar in males and females. A low-fat diet slows progression of renal injury in male and female pcy mice, consistent with findings in the male Han:SPRD-cy rat. Dietary fat type also influenced renal injury, with flaxseed oil diets rich in 18∶3n−3 slowing early fibrosis progression compared with diets rich in 18∶2n−6 or in 22∶6n−3.