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Because the mechanisms of (n-3) fatty acid-enriched triglyceride-rich particle [(n-3)-TGRP] uptake are not well characterized, we questioned whether (n-3)-TGRP are removed via "nonclassical" pathways, e.g., pathways other than an LDL receptor and/or involving apolipoprotein E (apoE). Chylomicron-sized model (n-3)-TGRP labeled with [3H]cholesteryl ether were injected into wild-type (WT) and CD36 knockout (CD36-/-) mice at low, nonsaturating and high, saturating doses. Blood clearance of (n-3)-TGRP was determined by calculating fractional catabolic rates. At saturating doses, blood clearance of (n-3)-TGRP was slower in CD36-/- mice relative to WT mice, suggesting that in part CD36 contributes to (n-3)-TGRP uptake. To further examine the potential nonclassical clearance pathways, peritoneal-elicited macrophages from WT and CD36-/- mice were incubated with (n-3)-TGRP in the presence of apoE, lactoferrin, and/or sodium chlorate. Cellular (n-3)-TGRP uptake was measured to test the roles of apoE-mediated pathways and/or proteoglycans. ApoE-mediated pathways compensated in part for defective (n-3)-TGRP uptake in CD36-/- cells. Lactoferrin decreased (n-3)-TGRP uptake in the presence of apoE. Inhibition of cell proteoglycan synthesis by chlorate reduced (n-3)-TGRP uptake in both groups of macrophages, and chlorate effects were independent of apoE. We conclude that although CD36 is involved, it is not the primary contributor to the blood clearance of (n-3)-TGRP. The removal of (n-3)-TGRP likely relies more on nonclassical pathways, such as proteoglycan-mediated pathways. [ABSTRACT FROM AUTHOR]

The metabolic syndrome is defined as the coexistence of 3 or more components, some of which indicate alterations in glucose and lipid metabolism. The prevalence of the metabolic syndrome is rapidly increasing in relation to obesity, and it is considered to be an important predictor of cardiovascular disease. Increased intakes or supplements of n-3 marine fatty acids may improve defects in insulin signaling and prevent alterations in glucose homeostasis and the further development of type 2 diabetes. This is largely mediated through a reduction in fatty acid accumulation in muscle and liver. n-3 Polyunsaturated fatty acids (n-3 PUFAs) reduce plasma triacylglycerols and improve the lipoprotein profile by decreasing the fraction of atherogenic small, dense LDL. However, n-3 PUFAs do not lower LDL cholesterol. These effects are likely mediated through the activity of transcription factors relating to expression of genes involved in lipid oxidation and synthesis. Other pleiotrophic effects of n-3 PUFAs may contribute to decreasing the burden of the metabolic syndrome, such as modulating inflammation, platelet activation, endothelial function, and blood pressure. Although studies comparing the effect of both major n-3 PUFAs are limited, docosahexaenoic acid appears at least as efficient as eicosapentaenoic acid in correcting several risk factors. The use of n-3 PUFAs should be considered in more global strategies including changes in lifestyle, such as adhering to a healthy Mediterranean type of diet and practicing regular physical exercise. Copyright © 2006 American Society for Nutrition [ABSTRACT FROM AUTHOR]

Background & Aims: Medium-chain triglycerides (TG) (MCT) and fish oil (FO) TG are incorporated as the core TG component into intravenous (IV) lipid emulsions for infusion in parenteral nutrition. Bolus injections of IV emulsions, on the other hand, have emerged as a novel therapeutic approach to treat various acute disorders. However, intravascular metabolism and organ delivery of acute IV injection of emulsions containing both MCT and FO are not fully defined, nor have they been characterized across common experimental animal models. We characterized and compared blood clearance kinetics and organ distribution of bolus injections of MCT/FO emulsions among different animal species. We also examined whether sex differences or feeding status can affect catabolic properties of MCT/FO lipid emulsions., Design: Blood clearance rates of lipid emulsions with specific TG composition were compared in rats IV injected with [3H]cholesteryl hexadecyl ether labeled pure n-6 long-chain (LCT) and n-3 FO TG lipid emulsions, or emulsions containing MCT and FO at different ratios (wt/wt), which include 8:2 (80% MCT: 20% FO), 5:4:1 (50% MCT: 40% LCT: 10% FO) and SMOF (30% LCT: 30% MCT: 25% olive oil: 10% FO). Dose-response effects (0.016 mg-1.6 mg TG/g body weight) of the MCT/FO 8:2 emulsions on blood clearance properties and organ delivery were determined in both mice and rats. Blood clearance kinetics and organ uptake of MCT/FO 8:2 emulsions were compared between male and female rats and between fed and fasted rats. Changes in plasma lipid profiles after acute injections of MCT/FO 8:2 lipid emulsion at different doses (0.043, 0.133, and 0.4 mg TG/g body weight) were characterized in non-human primates (Cynomolgus monkeys)., Results: MCT/FO 8:2 emulsion was cleared faster in rats when compared with other emulsions with different TG contents. Mice had faster blood clearance and higher fractional catabolic rates (FCR) when compared with the rats injected with MCT/FO 8:2 emulsions regardless of the injected doses. Mice and rats had similar plasma TG and free fatty acid (FFA) levels after low- or high-dose injections of the MCT/FO emulsion. Tissue distribution of the MCT/FO 8:2 lipid emulsion are comparable between mice and rats, where liver had the highest uptake per recovered dose among all organs (>60%). Feeding status and sex differences did not alter the blood clearance rate of the MCT/FO 8:2 emulsion in rats. In a nonhuman primate model, dose-response increases in plasma TG and FFA were observed after IV injection of MCT/FO 8:2 emulsions within the 1st 10 min., Conclusion: A lipid emulsion containing both MCT and FO TG is cleared rapidly in blood and readily available for organ uptake in rodent and primate animal models. Characterization of the blood clearance properties of the MCT/FO 8:2 emulsion administered in various animal models may provide further insight into the safety and efficacy profiles for future therapeutic use of bolus injections of MCT/FO emulsions in humans., Competing Interests: Conflicts of interest R.J.D. is a founding scientist and member of the scientific advisory board of DeckTherapeutics, Inc., a company developing diglyceride lipid emulsions to prevent tissue death after ischemic organ injuries. R.J.D. is an inventor on Columbia University assigned patents on omega-3 rich diglyceride emulsions as potential agents for cytoprotection of different organs after ischemic injury. Y.A.C. is founder and director of Nutrition Lipid Developments, SPRL, a company that aims to develop novel lipid emulsions for therapeutic applications. The other authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

This article reviews novel approaches for omega-3 fatty acid (FA) therapeutics and the linked molecular mechanisms in cardiovascular and central nervous system (CNS) diseases. In vitro and in vivo research studies indicate that omega-3 FAs affect synergic mechanisms that include modulation of cell membrane fluidity, regulation of intracellular signaling pathways, and production of bioactive mediators. We compare how chronic and acute treatments with omega-3 FAs differentially trigger pathways of protection in heart, brain, and spinal cord injuries. We also summarize recent omega-3 FA randomized clinical trials and meta-analyses and discuss possible reasons for controversial results, with suggestions on improving the study design for future clinical trials. Acute treatment with omega-3 FAs offers a novel approach for preserving cardiac and neurological functions, and the combinations of acute treatment with chronic administration of omega-3 FAs might represent an additional therapeutic strategy for ameliorating adverse cardiovascular and CNS outcomes.

The development of intravenous fat emulsion (IVFE) is the culmination of physiological, biochemical, nutritional, and medical scientific advancements. IVFEs have the ability to deliver critical nutritional substrates to the patient. Recent literature purports that they may also play roles in modulation of immune functionality and pulmonary physiology, but data supporting these potential benefits are limited. While soybean-based IVFEs have comprised the dominant fat in U.S. markets, a number of other novel IVFEs may prove to optimize the care of children and adults in both hospitalized and home settings. The October 2013 U.S. Food and Drug Administration (FDA)/American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Public Workshop brought together scientists, researchers, and clinical experts to present updated clinical perspectives of IVFEs, including historical development, current state of usage throughout the world, and considerations for the regulatory approval of new IVFEs in the United States., (© 2014 American Society for Parenteral and Enteral Nutrition.)

While a number of pathways for the catabolism and tissue delivery of intravenous lipid emulsions are shared by chylomicrons, there are also important differences. The introduction of medium-chain triglycerides (MCTs) and n-3 fatty acid-containing fish oils into lipid emulsions has marked effects on their clearance from the bloodstream and the delivery of fatty acids to organs, and it involves pathways different from those required for n-6 fatty acid-rich soybean oil-based particles. 1) Multiple pathways are responsible for the blood clearance and tissue uptake of MCT- and fish oil-containing emulsions. 2) Both human and animal model-based studies were needed to define these 'classical' and 'novel' pathways, which are respectively similar to and different from those involved in chylomicron clearance. 3) n-3 fatty acid-rich triglycerides and MCTs provide new opportunities for lipid emulsions to act as metabolic and immune modulators., (© 2015 S. Karger AG, Basel.)

Objective: To investigate the effect of a natural cholesterol-lowering supplement (NCLS) containing red yeast rice, policosanols and artichoke leaf extracts on blood lipid concentrations as well as on safety parameters when given over 16 weeks in 100 volunteers with untreated moderate hypercholesterolemia, in a randomized, double-blind, placebo-controlled trial., Results: Reduction of primary outcome low-density lipoprotein cholesterol [-0.22 g/L (95% confidence interval, CI: -0.31 to -0.12) corresponding to -14.3% from baseline (95% CI: -21.5 to -7.2) compared to placebo], as well as total cholesterol, apolipoprotein B100 and apolipoprotein B100/apolipoprotein A-I ratio, were observed after 16 weeks of supplementation with NCLS. These effects were already observed at Week 4 and 10 of supplementation. No significant changes were observed in high-density lipoprotein, triacylglycerol, creatine kinase, lactate dehydrogenase and coenzyme Q10 levels, as well as in markers of liver and renal function., Conclusions: The NCLS was effective in reducing low-density lipoprotein cholesterol and apolipoprotein B100 in subjects with moderate hypercholesterolemia, without modifying safety parameters.

Scope: Recent data suggest that gut microbiota contributes to the regulation of host lipid metabolism. We report how fermentable dietary fructo-oligosaccharides (FOS) control hepatic steatosis induced by n-3 PUFA depletion, which leads to hepatic alterations similar to those observed in non-alcoholic fatty liver disease patients., Methods and Results: C57Bl/6J mice fed an n-3 PUFA-depleted diet for 3 months were supplemented with FOS during the last 10 days of treatment. FOS-treated mice exhibited higher caecal Bifidobacterium spp. and lower Roseburia spp. content. Microarray analysis of hepatic mRNA revealed that FOS supplementation reduced hepatic triglyceride accumulation through a proliferator-activated receptor α-stimulation of fatty acid oxidation and lessened cholesterol accumulation by inhibiting sterol regulatory element binding protein 2-dependent cholesterol synthesis. Cultured precision-cut liver slices confirmed the inhibition of fatty acid oxidation. FOS effects were related to a decreased hepatic micro-RNA33 expression and to an increased colonic glucagon-like peptide 1 production., Conclusions: The changes in gut microbiota composition by n-3 PUFA-depletion and prebiotics modulate hepatic steatosis by changing gene expression in the liver, a phenomenon that could implicate micro-RNA and gut-derived hormones. Our data underline the advantage of targeting the gut microbiota by colonic nutrients in the management of liver disease., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The present review aims at highlighting the use of a recently developed medium-chain triacylglycerol:fish oil (MCT:FO) emulsion for the rapid and sustained enrichment of long-chain polyunsaturated ω-3 fatty acids in cell phospholipids. Preclinical in vitro, in vivo, and ex vivo experiments are briefly considered with emphasis on the changes in the fatty acid pattern of cell phospholipids in several organs, the partial correction of liver steatosis, and the cardiovascular modification of cationic and functional variables observed in ω-3-depleted rats examined 60-120 minutes after a bolus intravenous (IV) injection (1.0 mL) of the MCT:FO emulsion. The clinical findings collected in healthy male volunteers before or after the bolus IV injection (50.0 mL) of either the MCT:FO emulsion or a control medium-chain triacylglycerol:long-chain triacylglycerol emulsion are also reviewed, with emphasis on the rapid (within 60 minutes) and sustained (up to 2-3 days) enrichment of platelet and white blood cell phospholipids in long-chain polyunsaturated ω-3 fatty acids and hemostatic safety of the present procedure proposed as a tool for the rapid prevention or correction of metabolic and functional disturbances in humans with a relative deficiency in such ω-3 fatty acids.

Second generation n3-PUFA-depleted rats represent a good animal model of metabolic syndrome as they display several features of the disease such as liver steatosis, visceral obesity and insulin resistance. The goal of our study was to investigate the influence of n3-PUFA deficiency on hepatic glycerol metabolism. Aquaglyceroporin 9 (AQP9) allows hepatic glycerol transport and consequently contributes to neoglucogenesis. AQP9 knockout mice display hypertriacyl-glycerolemia, one of the hallmarks of the metabolic syndrome. Our data show reduced AQP9 expression at the protein level in n3-PUFA-depleted rats, without any changes at the mRNA levels. [U-¹⁴C]glycerol uptake was increased in hepatocytes from n3-PUFA-depleted animal cells. The apparent discrepancy between decreased AQP9 protein expression, and increased [U-¹⁴C]glycerol uptake could be explained by an observed increase in glycerol kinase activity.

Aquaglyceroporin 7 (AQP7) is a glycerol transporter expressed in adipocytes. Its expression has been shown to be modulated in obesity. Metabolic syndrome is characterized by abdominal obesity, insulin resistance, dyslipidemia, and hypertension. An animal model displaying several features of metabolic syndrome was used to study the AQP7 expression at both mRNA and protein level and glycerol flux in adipocytes. Second generation n3-PUFA depleted female rats is a good animal model for metabolic syndrome as it displays characteristic features such as liver steatosis, visceral obesity, and insulin resistance. Our data show a reduced expression of AQP7 at the protein level in adipose tissue from n3-PUFA-depleted rats, without any changes at the mRNA levels. [U-(14)C]-Glycerol uptake was not modified in adipocytes from n3-PUFA-depleted animals., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Western diet is characterized by an insufficient n-3 polyunsaturated fatty acid (PUFA) consumption which is known to promote the pathogenesis of several diseases. We have previously observed that mice fed with a diet poor in n-3 PUFA for two generations exhibit hepatic steatosis together with a decrease in body weight. The gut microbiota contributes to the regulation of host energy metabolism, due to symbiotic relationship with fermentable nutrients provided in the diet. In this study, we have tested the hypothesis that perturbations of the gut microbiota contribute to the metabolic alterations occurring in mice fed a diet poor in n-3 PUFA for two generations (n-3/- mice)., Methods: C57Bl/6J mice fed with a control or an n-3 PUFA depleted diet for two generations were supplemented with prebiotic (inulin-type Fructooligosaccharides, FOS, 0.20 g/day/mice) during 24 days., Results: n-3/-mice exhibited a marked drop in caecum weight, a decrease in lactobacilli and an increase in bifidobacteria in the caecal content as compared to control mice (n-3/+ mice). Dietary supplementation with FOS for 24 days was sufficient to increase caecal weight and bifidobacteria count in both n-3/+ and n-3/-mice. Moreover, FOS increased lactobacilli content in n-3/-mice, whereas it decreased their level in n-3/+ mice. Interestingly, FOS treatment promoted body weight gain in n-3/-mice by increasing energy efficiency. In addition, FOS treatment decreased fasting glycemia and lowered the higher expression of key factors involved in the fatty acid catabolism observed in the liver of n-3/-mice, without lessening steatosis., Conclusions: the changes in the gut microbiota composition induced by FOS are different depending on the type of diet. We show that FOS may promote lactobacilli and counteract the catabolic status induced by n-3 PUFA depletion in mice, thereby contributing to restore efficient fat storage.

Background: Mild iodine deficiency (MID) is endemic in Belgium. Previous surveys, which assessed iodine nutrition in Belgium, focused on children. The iodine status of adults and the influence of ethnicity or seasonality on urinary iodine concentrations (UIC) have not been investigated. Since the nutritional profile of children differs from that of adults, we may anticipate similar differences in iodine status. Seasonal fluctuations in UIC have also been reported from other MID regions., Aim of the Study: We aimed at assessing iodine status and its association with ethnicity and seasonality in adults., Methods: A stratified random sample of 401 healthy subjects aged between 40 and 60 years, of Belgian, Moroccan, Turkish and Congolese descent residing in Brussels was obtained. Iodine status and thyroid function were determined., Results: Median UIC was 68 μg/L. The frequency of UIC below 100 μg/L was 73.3%, of which 41.9% fell between 50 and 99 μg/L, and 29.8% between 49 and 20 μg/L. There was no difference in UIC and thyroid function between subjects of different ethnic origins. The frequency of UIC below 50 μg/L was higher in the fall-winter compared to spring-summer periods (P = 0.004). Serum FT3 concentrations, but not FT4 and TSH, were significantly greater in winter than in summer., Conclusion: Seasonal fluctuations in UIC suggest that the risk of iodine deficiency among adults living in Brussels is higher in fall-winter than in spring-summer. The prevalence of MID in Brussels is high among adults but ethnicity does not appear to influence iodine status.

Patients with non-alcoholic fatty liver disease are characterised by a decreased n-3/n-6 polyunsaturated fatty acid (PUFA) ratio in hepatic phospholipids. The metabolic consequences of n-3 PUFA depletion in the liver are poorly understood. We have reproduced a drastic drop in n-3 PUFA among hepatic phospholipids by feeding C57Bl/6J mice for 3 months with an n-3 PUFA depleted diet (DEF) versus a control diet (CT), which only differed in the PUFA content. DEF mice exhibited hepatic insulin resistance (assessed by euglycemic-hyperinsulinemic clamp) and steatosis that was associated with a decrease in fatty acid oxidation and occurred despite a higher capacity for triglyceride secretion. Microarray and qPCR analysis of the liver tissue revealed higher expression of all the enzymes involved in lipogenesis in DEF mice compared to CT mice, as well as increased expression and activation of sterol regulatory element binding protein-1c (SREBP-1c). Our data suggest that the activation of the liver X receptor pathway is involved in the overexpression of SREBP-1c, and this phenomenon cannot be attributed to insulin or to endoplasmic reticulum stress responses. In conclusion, n-3 PUFA depletion in liver phospholipids leads to activation of SREBP-1c and lipogenesis, which contributes to hepatic steatosis.

Docosahexaenoic acid (C22:6ω3) generated in the liver from circulating α-linolenic acid (C18:3ω3) was recently proposed as the source of brain C22:6ω3 when the latter fatty acid is absent from the diet. The present study aims at exploring whether a comparable situation prevails in Types 1 and 2 diabetic rats, even when exposed to a normal diet. The fatty acid profile of liver, plasma and brain phospholipids (PL) was examined in 22 rats including 6 streptozotocin-induced diabetic animals (Type 1 diabetes), 8 Goto-Kakizaki rats (Type 2 diabetes) and 8 control animals. Both fed and overnight starved rats of both genders were included in this study. To avoid the interference of any group effect, all individual results were expressed relative to the mean value found in animals of the same gender, same strain, same nutritional situation and same glycemic status, such results being referred to as normalized values. Significant positive correlations were observed between the normalized values for the C22:6ω3 relative weight content of liver and plasma PL and, after exclusion of 2 female control rats with an abnormally high brain/plasma PL C22:6ω3 ratio, plasma and brain PL. Noticeably, the variation coefficients (SD/mean) for the 3 variables did not exceed 7.1±1.8%. A comparable situation prevailed between liver, plasma and brain triglycerides. Our results suggest that circulating PL participate in the transfer of C22:6ω3 from the liver to the brain, even in control and diabetic rats not deprived of a dietary source of long-chain polyunsaturated ω3 fatty acids.

Background: Dietary deficiency in n-3 (omega-3) polyunsaturated fatty acids (PUFAs) prevails in Western populations and potentially results in adverse health outcomes. To circumvent the slow n-3 PUFA incorporation in phospholipids of key cells after oral supplementation, a new preparation for intravenous bolus injection was developed with 20 g triacylglycerols/100 mL of a mixture of 80% medium-chain triacylglycerols (MCTs) and 20% fish oil (FO) (wt:wt), and 0.4 g alpha-tocopherol/100 mL of the same mixture., Objective: Our objective was to document the enrichment of n-3 PUFAs in leukocyte and platelet phospholipids after a bolus intravenous injection of MCT:FO in men., Design: Twelve healthy male subjects received injections over a 5-min period of 50 mL of either MCT:FO or a control MCT:long-chain triacylglycerol (MCT:LCT) emulsion containing 20 g triacylglycerols/100 mL with equal amounts (wt:wt) of MCT and soybean triacylglycerols (LCT) and containing 0.02 g alpha-tocopherol/100 mL; after an 8-wk interval, the subjects received injections of the other preparation., Results: Clinical and biological variables that assessed tolerance and safety remained unchanged. Plasma elimination was faster for MCT:FO than for MCT:LCT (half-life: 24.5 +/- 3.5 min compared with 32.9 +/- 3.0 min; P < 0.025). This was associated with a greater increase in the plasma nonesterified fatty acid concentration. The content of n-3 PUFAs, specifically eicosapentaenoic acid (20:5n-3), increased in leukocyte and platelet phospholipids within 60 min and > or =24 h after MCT:FO injection., Conclusion: Bolus intravenous injection of a novel MCT:FO emulsion allows rapid enrichment of cells with n-3 PUFAs.

Perturbations of fatty acid content and pattern were recently documented in epididymal and parametrial lipids, as well as plasma, liver, spleen, and brain phospholipids and triglycerides of Goto-Kakizaki rats (GK). This study extends such an investigation to pancreatic islets from both control and GK rats. Groups of 5,500-14,560 islets were obtained from either control or GK rats (n = 3 in each case) and examined for their lipid fatty acid content. In the islet triglycerides, the major difference between control and GK rats, i.e., a higher C18:2ω6 content in GK rats, was similar to that found in liver triglycerides. In the islet phospholipids, however, a number of differences between control and GK rats, concerning saturated, monodesaturated, and long-chain polyunsaturated ω3 and ω6 fatty acids, were often not similar to those found in liver phospholipids. The present study reveals a number of anomalies in the fatty acid pattern of islet phospholipids in GK rats, often differing from those encountered in liver phospholipids. Such a tissue specificity was borne out by the finding that, even in control animals, the situation found in islet phospholipids differed from that recorded in liver phospholipids.

Exposure of normal rats for 3-7 months to an omega3-deprived diet and subsequent exposure to an omega3-enriched diet were recently proposed as a model to study the metabolic consequences of alteration in the dietary supply of omega3 PUFA and their time course. The same animal model was used in the present study, which aimed at characterizing the pattern of saturated and monodesaturated fatty acids in the phospholipids of the duodenum, jejunum, caecum and colon. With one exception (C18:0), the weight content of these fatty acids was lower in the proximal than distal intestinal segments, a situation possibly accounted for by the generation of short-chain fatty acids by the colonic flora and the resulting synthesis of longer fatty acids n colonocytes. The relative weight content of the 8 fatty acids under consideration (C14:0, C16:0, C16:1omega7, C18:0, C18:1omega9, C20:0, C22:0 and C24:0) was higher in the phospholipids of omega3-deprived rats, as compared to control animals. Exposure of either the control animals or omega3-deprived rats for 2-4 weeks to diets containing twice more lipids than the control or omega3-deprived diet given theretofore further increased, as a rule, the relative content of phospholipids in the saturated or monodesaturated fatty acids, such an increase being much more pronounced in the proximal segments of the intestinal tract than in the distal ones. A significant inverse correlation between the phospholipid content in C22:6omega3 and saturated and monodesaturated fatty acids was only observed in the caecum and colon.

This study aims mainly at investigating the effects of a dietary deprivation and replenishment of omega3 PUFA upon the phospholipid pattern of omega6 PUFA in the duodenum, jejunum, caecum and colon of rats exposed for 3-7 months to an omega3-depleted diet and then eventually exposed for 2-4 weeks to an omega3-rich diet. In control rats, the relative weight content of all omega6 fatty acids differed in the proximal and distal intestinal segments. In the omega3-depleted rats the C18:2omega6, C20:2omega6 and C20:3omega6 content was decreased whilst that of C20:4omega6 and C22:4omega6 was increased. Significant correlations were found in the caecum or colon between the C18:2omega6 or C20:4omega6 content of intestinal phospholipids and their C22:6omega3 content, an increase in the latter content coinciding with an increase in C18:2omega6 and decrease of C20:4omega6. Such was also the case for C20:4omega6, but not C18:2omega6, in the duodenum and jejunum. At these proximal intestinal levels, exposure of the omega3-depleted rats to a flaxseed oil-enriched diet indeed decreased the C18:2omega6 phospholipid content, an effect possibly attributable to the much lower content of C18:2omega6 in the latter diet, as distinct from the sunflower diet offered to the omega3-depleted rats during the first 7 months. However, at more distal intestinal levels, and like in the liver, a deficiency in omega3 fatty acids apparently favours the stepwise conversion of C18:2omega6 to C20:4omega6 and C22:4omega6.

A dietary deprivation in long-chain polyunsaturated omega3 fatty acids initiated in 7-week old normal rats provokes within 3 to 7 months the appearance of several features of the metabolic syndrome. Likewise, within 2 to 4-5 weeks exposure to a flaxseed oil-enriched diet, these anomalies are rapidly corrected. The present study deals with the omega3 fatty acid content of intestinal phospholipids under the same experimental conditions. For the sake of comparison, the control rats were given access during the last 4-5 weeks to either a soybean or flaxseed oil-enriched diet. In control rats, the relative weight content of omega3 fatty acids as well as their product/precursor ratio differed in distinct segments of the intestinal tract (duodenum, jejunum, caecum, colon). Within 3 months of omega3-deprivation, the intestinal content of C18:3omega3, C20:5omega3 and C22:5omega3 reached values below the limit of detection, whilst the C22:6omega3 content progressively decreased down to 10-20% of control values. Within 2 weeks of exposure to the omega3-rich diet, the C18:3omega3, C20:5omega3 and C22:5omega3 content of intestinal phospholipids were higher than control values, whilst that of C22:6omega3 progressively returned to a normal level during the 2 to 4-5 weeks exposure to the flaxseed oil-enriched diet. The results collected in the intestinal cells, which are the first cells exposed to each given diet, reinforce the view that the present animal model is quite suitable to assess the metabolic consequences of both omega3 fatty acid deprivation and replenishment.

The bolus intravenous injection of a medium-chain triglyceride:fish oil emulsion was recently found to increase within 60 min the cell phospholipid content in long-chain polyunsaturated omega3 fatty acids and, hence, proposed as a potential tool to prevent cardiac arrhythmia in subjects with a decreased dietary intake of such fatty acids. In the present study, ventricular cardiomyocytes from second generation rats depleted in omega3 fatty acids were found to display the same changes in the phospholipid fatty acid pattern as that previously documented in the cardiac muscle and endothelium of such rats, altered 86Rb and 45Ca fluxes with emphasis on a decrease in both K+ inflow and K+ content and an increase in both Ca2+ inflow and content. The alteration of K+ inflow could not be attributed to a decrease in ouabain-sensitive Na+,K+-ATPase activity as measured in cell homogenates. The cationic alterations were corrected, in part at least, by the prior intravenous injection of the medium-chain triglyceride:fish oil emulsion 60 min before sacrifice of the omega3-depleted rats.

Rats exposed from 7 weeks after birth and for the ensuing 3 to 7 months to a diet depleted in long-chain polyunsaturated omega3 fatty acids were recently proposed as a new animal model for the metabolic syndrome. The present study aimed mainly at investigating whether, in this new model, the perturbation of the fatty acid total content and pattern of brain phospholipids simulates that previously documented in second-generation omega3-depleted rats. Such was indeed the case, with the apparent exception of changes in the C18:1omega9, C20:0, C22:0 and C24:0 relative content of brain phospholipids. Moreover, the C22:5omega3 content of such phospholipids was unexpectedly lower in the present model than in the second-generation omega3-depleted rats. The changes in brain phospholipids were also monitored when the rats deprived of omega3 fatty acids for 7 months were given access for 2 to 4-5 weeks to a flaxseed oil-enriched diet. Most phospholipid variables were rapidly normalized under the latter experimental conditions. The results obtained under these conditions suggest that an increase in the brain phospholipid C22:5omega3 content may play a key role in the orexigenic effects of exogenous omega3 fatty acids supplied to omega3-depleted animals.

The mechanism, by which a high-fat (HF) diet could impair glucose metabolism, is not completely understood but could be related to inflammation, lipotoxicity and oxidative stress. Lipid peroxides have been proposed as key mediators of intracellular metabolic response. The purpose of the present study was to analyse, in mice fed with a HF diet, the possible association between obesity and glucose tolerance on the one hand, and between oxidative stress and lipid peroxidation on the other hand. The present results show that a HF diet (70 % energy as fat), v. a high-carbohydrate chow diet (control), increases body weight and fat mass development, and impairs glycaemia and insulinaemia within 4 weeks. It also promotes the expression of NADPH oxidase in the liver--signing both oxidative and inflammatory stress--but decreases thiobarbituric acid-reactive substances content in the liver as well as in epididymal, subcutaneous and visceral adipose tissues. HF diet, with elevated vitamin E content, induces high concentration of alpha-tocopherol in liver and adipose tissues, which contributes to the protection against lipid peroxidation. Thus, lipid peroxidation in key organs is not necessarily related to the development of metabolic disorders associated with diabetes and obesity.

Second-generation rats depleted in long-chain polyunsaturated omega3 fatty acids were recently proposed as a novel animal model for the metabolic syndrome. In the present study, a dietary deprivation of omega3 acids for 3-7 months was found sufficient to provoke in 6-week-old normal rats the same alteration of the fatty acid content and profile of liver phospholipids and triglycerides as that otherwise prevailing in the second-generation omega3-depleted rats, with emphasis on a severe decrease in their omega3 fatty acid content, alterations in the relative contribution of and ratio between selected long-chain polyunsaturated omega6 fatty acids, saturated and monodesaturated fatty acids and precursors of nervonic acid, and liver steatosis. When the omega3-depleted rats were exposed, after the first 7 months of the present experiments and for 2-4 weeks to a diet supplemented with 5% (w/w) flaxseed oil, most of these hepatic variables returned towards or beyond control values. In both the omega3-depleted rats and control animals, however, the eventual exposure to the flaxseed oil-enriched diet failed to suppress liver steatosis and, on the contrary, provoked a further increase in liver triglyceride content. It is proposed, therefore, that the present approach represents a simple and realistic animal model to study the consequences of omega3-depletion. Moreover, the results suggest that to oppose such consequences, e.g. liver steatosis, it may be necessary to combine the dietary supply of omega3 acids with a suitable control of food intake, in both qualitative and quantitative terms.

Exposure of 7-week-old normal rats for 3-7 months to a diet deprived of long-chain polyunsaturated omega3 fatty acids was recently reported to induce changes in the fatty acid content and pattern of liver phospholipids and triglycerides similar to those otherwise found in second generation omega3-depleted rats. In the present study, the changes in body weight, parametrial adipose tissue mass, plasma glucose and insulin concentrations and insulin resistance index were investigated in the same control and omega3-depleted rats, which were then given access for 2 to 4-5 weeks to either a flaxseed oil-enriched diet (control and omega3-depleted rats) or a soybean oil-enriched diet (control rats). The body weight failed to differ between control and omega3-depleted rats. The latter rats, however, displayed increases in adipose tissue mass, plasma glucose and insulin concentrations, and insulin resistance index. In the control rats given access to the soybean or flaxseed oil-enriched diet, body weight and adipose tissue mass were little affected, but both the plasma glucose concentration and insulin resistance index decreased. In the omega3-depleted rats given access to the flaxseed oil-enriched diet, both body weight and adipose tissue mass underwent a rapid, pronounced and sustained increase, whilst the plasma glucose concentration and insulin resistance index decreased similarly to those in the control rats. The present design of omega3 fatty acid dietary deprivation thus reproduces the visceral obesity and insulin resistance otherwise observed in second-generation omega3-depleted rats. However, the supply of exogenous omega3 fatty acids to the omega3-depleted rats failed to oppose visceral obesity, possibly as a result of the orexigenic effects of these omega3 fatty acids.

The outcome of a total dietary approach using a wide range of n-3 polyunsaturated fatty acids (PUFA) enriched food items on cardiovascular diseases called for further investigation. The study objective was to assess the effect of an ALA-enriched food supply on cardiovascular risk factors in healthy males. A dietary intervention (single-blind field trial with pre- and post-measurements) was performed with 59 healthy males in a Belgian prison. Over a period of 12 weeks they were supplied with an n-3 enriched diet (containing 6.5 g n-3 PUFA/day compared to 4 g n-3 PUFA/day in the standard diet) that was substituted for their regular diet, increasing mainly the alpha-linolenic acid intake (from 2.8 to around 5 g/day). The results indicated no impact on subjects waist circumference, weight and BMI or systolic blood pressure. In contrast, the diastolic blood pressure significantly decreased during the intervention period (from 74.6 +/- 8.2 to 71.7 +/- 10.1 mmHg; P < 0.02). Moreover, the HDL-cholesterol level increased in non-smoking participants (from 0.97 +/- 0.25 to 1.06 +/- 0.23 mmol/l; P < 0.03). In summary, the study demonstrated that enrichment of commonly eaten food items with n-3 fatty acids provides the opportunity to increase the n-3 fatty acid intake and to decrease the n-6/n-3 ratio which results in a decreasing diastolic blood pressure and an increase of HDL-cholesterol (in non-smokers).

The long-term metabolic and functional effects of a dietary deprivation of long-chain polyunsaturated omega3 fatty acids were recently investigated in second-generation omega3-depleted rats. This study represents the first attempt to explore the direct, but not immediate, effects of omega3 fatty acids on insulin-producing cells. For this purpose, BRIN-BD11 cells were cultured for 24 h in the absence or presence of both C20:5omega3 and C22:6omega3 (50 microM each) and, thereafter, examined for their phospholipid and triglyceride fatty acid pattern, and their metabolic, ionic, and secretory responses to D: -glucose and/or non-nutrient insulinotropic agents. The prior culture in the presence of the two omega3 fatty acids provoked an enrichment of cell lipids in such omega3 fatty acids, changes in the phospholipid fatty acid pattern of long-chain polyunsaturated omega6 fatty acids as well as saturated and monodesaturated fatty acids, and cell steatosis. It minimized the relative increase in D: -[5-(3)H]glucose utilization and D: -[U-(14)C]glucose oxidation otherwise resulting from an increase in the concentration of the hexose from 1.1 to 11.1 mM. It also minimized the changes in (86)Rb(+) net uptake otherwise provoked by rises in D: -glucose concentration and decreased the absolute values for insulin output. It is concluded that the major changes in metabolic, cationic, and secretory behavior of the omega3-enriched BRIN-BD11 cells are paradoxically similar to those encountered in pancreatic islets from omega3-depleted rats and, in both cases, possibly attributable to a phenomenon of lipotoxicity.

Background: The study of vitamin D status at population level gained relevance since vitamin D deficiency was recently suggested to trigger chronic disease., Aim of the Study: We aimed to describe vitamin D status, its association with bone and mineral metabolism and risk factors for deficiency in adults over 40 years in Belgium., Methods: We conducted a cross-sectional survey in a stratified random sample of 401 subjects aged between 40 and 60 years living in Brussels, and drawn from 4 different ethnic backgrounds: autochthonous Belgian, Moroccan, Turkish and Congolese. 25-Hydroxyvitamin D (25OHD), parathyroid hormone (PTH), osteocalcin, C-telopeptide and bone mineral density was measured., Results: Three-hundred and six subjects (77%) showed 25OHD concentrations below 50 nmol/l,135 (34%) below 25 nmol/l and 18 (5%) below 12.5 nmol/l. The proportion of subjects with vitamin D deficiency was four times greater amongst those of Moroccan or Turkish descent compared with those of Congolese or Belgian descent. Moroccan subjects showed a significant higher PTH and bone marker concentrations compared to Belgian. Ethnicity, season and sex were independently associated with vitamin D deficiency in multivariate analysis., Conclusion: The prevalence of vitamin D deficiency is very high amongst the adult population of Brussels but immigrants are at greater risk. Given the established link between population health and adequate vitamin D status, a policy of vitamin D supplementation should be considered in these risk groups.

The bolus intravenous administration of a novel medium-chain triglyceride: fish oil emulsion (MCT:FO) to normal subjects was recently found to increase within 60 min the amount of long-chain polyunsaturated omega3 fatty acids ( omega3) in platelet and leukocyte phospholipids and, hence, was proposed as a tool to prevent such pathological events as cardiac arrhythmia in selected patients who have to undergo urgent anesthesia and/or surgery. This study investigates whether other cells located outside the vascular bed may also benefit from this procedure for replenishing phospholipids with omega3. For such a purpose, the MCT:FO emulsion (1.0 ml) was injected into normal or omega3-depleted rats examined, one hour later, for the content and fatty acid pattern of liver triglycerides and phospholipids. Control experiments included the administration of saline or a medium-chain triglyceride:olive oil emulsion. The results reveal that the bolus intravenous injection of MCT:FO to the omega3-depleted rats resulted in the enrichment of liver phospholipids in omega3 and a marked reduction in hepatic steatosis. In conclusion, it is proposed that such a procedure may indeed allow a rapid supply of omega3 not only to circulating and vascular endothelial cells but also to extravascular cells, with a resulting correction of the biochemical and biophysical defects linked to a deficiency in these fatty acids.

Considering the numerous features of the metabolic syndrome found in rats depleted in long-chain polyunsaturated (n-3) fatty acids and in the perspective of further work conducted in (n-3)-depleted mice, the fatty acid profile of plasma and liver lipids was assessed in both male and female control and second-generation (n-3)-depleted mice. In addition to gender differences, the major alteration found in the (n-3)-depleted animals consisted in the expected severe depletion of plasma triacylglycerols and phospholipids, as well as liver phospholipids, in C20:5(n-3), C22:5(n-3) and C22:6(n-3). In plasma triacylglycerols, the weight percentages of C18:2(n-6) and C18:3(n-6) were lower in (n-3)-depleted mice than in control animals. In both plasma and liver phospholipids, however, the weight percentages of long-chain polyunsaturated (n-6) fatty acids (C20:4(n-6) and C22:4(n-6)) were higher in (n-3)-depleted mice than in control animals. The C16:1(n-7)/C16:0 and C18:1(n-9)/C18:0 ratio in both plasma and liver phospholipids were also increased in female (n-3)-depleted mice but not so in male animals. Highly significant correlations were found between the weight percentage of each fatty acid in liver versus plasma phospholipids. Taken as a whole, these findings indicate that second-generation mice depleted in (n-3) fatty acids represent a suitable model, in terms of the remodelling of the fatty acid profile in plasma and liver lipids, to investigate the metabolic and functional consequences of such a depletion.

The bolus intravenous injection of a novel 8:2 medium-chain triglyceride:fish oil emulsion was recently found to increase within 60 min and for the subsequent 24-48 h the long-chain polyunsaturated omega3 fatty acid content of both leucocyte and platelet phospholipids in 12 normal subjects. The aim of the present report is to document the hemostatic safety of such a procedure in the same 12 subjects. No adverse effect was found when comparing the results obtained after administration of either the fish oil-containing emulsion or a control 5:5 medium-chain triglyceride:soybean triglyceride emulsion, whether in terms of the occlusion time in either an ADP or epinephrine test or in terms of the [CD]42b, [CD]62p, fibrinogen and PAC-1 response to ADP, collagen or thrombin receptor analog peptide 6 in platelets examined by fluorescence activated cell sorting. In conclusion, this novel procedure for the rapid enrichment of cell phospholipid in long-chain polyunsaturated omega3 fatty acids presents the required safety in a hemostatic perspective.

Considering the changes in the fatty acid profile of liver lipids related to age, gender and nutritional status or occurring in pathological situations, this study aimed at investigating whether such changes could be judged from measurements conducted in plasma lipids. The fatty acid profile of both liver and plasma phospholipids and triglycerides was measured in 16 control animals and 26 rats depleted in long-chain polyunsaturated (n-3) fatty acids. Within each group of rats, significant correlations prevailed between the percentage of each fatty acid in liver versus plasma phospholipids or triglycerides. However, the plasma/liver ratio for the relative content of C20:5(n-3), C22:5(n-3) and C22:6(n-3) in triglycerides displayed abnormally high values in 2 control animals. The fatty acid profile of liver phospholipids and triglycerides can, as a rule, be judged from measurements made in the corresponding plasma lipids. For instance, measurements in plasma phospholipids could help to identify subjects deficient in (n-3) fatty acids and to assess the dietary correction of this defect.

Background: Lipolysis of a fish oil (FO) emulsion is much slower than that of a soybean [long-chain triacylglycerol (LCT)] emulsion; in contrast, emulsions containing medium-chain triacylglycerol (MCT) are efficiently hydrolyzed by lipoprotein lipase., Objectives: We questioned whether incorporating 10% FO in a mixed MCT-LCT emulsion would affect plasma triacylglycerol clearance and provide efficient delivery of n-3 polyunsaturated fatty acids to cells and tissues., Design: This prospective crossover study was conducted in 8 normolipidemic subjects with the use of the hypertriglyceridemic clamp model and compared plasma triacylglycerol clearance of a lipid emulsion (5:4:1) made of 50% MCT, 40% LCT, and 10% FO (wt:wt:wt) to a control (5:5) preparation with 50% MCT and 50% LCT. Subjects were daily infused for 5 h, over 4 consecutive days. Fatty acyl pattern was daily measured in plasma phospholipids as well as in leukocyte and platelet phospholipids., Results: Inclusion of 10% FO in mixed emulsion particles enhanced plasma clearance of infused triacylglycerols (18%; P < 0.0001). The faster elimination of the 5:4:1 emulsion appears related to an enhanced uptake of remnant particles rather than to faster intravascular lipolysis. Each infusion of 5:4:1 raised the eicosapentaenoic acid (C20:5n-3) concentration in blood cell phospholipids to reach a 7-fold enrichment in platelets and a >2-fold enrichment in leukocytes after 4 infusions. In contrast, the docosahexaenoic acid (C22:6n-3) concentration remained unchanged in blood cell phospholipids., Conclusions: Infusion of a mixed emulsion with MCTs, soy LCTs, and FO is associated with efficient plasma triacylglycerol clearance and results in rapid incorporation of C20:5n-3 but not C22:6n-3 in leukocyte and platelet phospholipids.

Considering the proposed preventive effect of nervonic acid on obesity- and diabetes-related coronary risk factors, the content of its precursors (oleic, 11-eicosenoic and 13-docosenoic acids) was measured in liver and plasma phospholipids and triglycerides, brain and spleen phospholipids, and adipose tissue lipids of fed or overnight fasted control and hereditarily diabetic Goto-Kakizaki female rats, as well as fed streptozotocin-induced diabetic female rats. In liver and brain phospholipids, the 11-eicosenoate/oleate ratio was significantly higher in diabetic rats than in control animals. Such was not the case in either spleen phospholipids or liver triglycerides and adipose tissue lipids. The increase in the liver phospholipid 11-eicosenoate/oleate ratio found in female diabetic rats represents a mirror image of the situation recently documented, in the same animal models of diabetes, in male rats. These contrasting findings may be relevant to the higher coronary heart disease risk prevailing in female, as compared to male, diabetic subjects.

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.

The bolus intravenous administration of a novel medium-chain triglyceride:fish oil emulsion to second generation rats depleted in long-chain polyunsaturated omega3 fatty acids was recently found to enrich within 60 min the content of both plasma and liver lipids in such omega3 fatty acids, this coinciding with correction of the perturbation in liver triglyceride fatty acid content and profile otherwise prevailing in these rats. The present report draws attention to cause-to-effect relationships between changes in liver phospholipid and triglyceride fatty acid content and/or pattern operative under these experimental conditions.

The bolus intravenous injection of a novel medium-chain triglyceride:fish oil emulsion to normal subjects was recently reported to enrich within 60 min the phospholipid content of leucocytes and platelets in long-chain polyunsaturated omega3 fatty acids. The present study, conducted in second generation omega3-depleted rats, aimed at investigating whether such a procedure may also increase within 60 min the phospholipid content of omega3 fatty acids in cells located outwards the bloodstream, in this case liver cells, and whether this coincides with correction of the perturbation in the liver triglyceride fatty acid content and profile otherwise prevailing in these rats. This first report deals mainly with the fatty acid pattern of plasma lipids in male omega3-depleted rats that were non-injected or injected with either the omega3-rich emulsion or a control medium-chain triglyceride:olive oil emulsion. The results provide information on the fate of the exogenous lipids present in the lipid emulsions and injected intravenously 60 min before sacrifice. Moreover, in the uninjected omega3-depleted rats the comparison between individual plasma and liver measurements indicated positive correlations in the fatty acid profile of phospholipids and triglycerides.

The metabolism of D-glucose was recently reported to be impaired in pancreatic islets from second generation rats depleted in long-chain polyunsaturated omega3 fatty acids. Considering the increased clearance of circulating non-esterified fatty acids prevailing in these rats, a possible inhibition of glucokinase in insulin-producing cells by endogenous long-chain fatty acyl-CoA was considered. The present study was mainly aimed at assessing the validity of the latter proposal. The activity of glucokinase in islet homogenates, as judged from the increase in D-glucose phosphorylation rate in response to a rise in the concentration of the hexose represented, in the omega3-depleted rats, was only 81.8 +/- 4.8% (n = 11; p < 0.005) of the paired value recorded in control animals. This coincided with the fact that the inclusion of D-glucose 6-phosphate (3.0 mM) and D-fructose 1-phosphate (1.0 mM) in the assay medium resulted in a lesser fractional decrease of D-glucose phosphorylation in omega3-depleted rats than in control animals. Moreover, whereas palmitoyl-CoA (50 microM) decreased the activity of glucokinase by 38.0 +/- 6.0% (n = 4; p < 0.01) in islet homogenates from normal rats, the CoA ester failed to affect significantly the activity of glucokinase in islet homogenates from omega3-depleted rats. These findings afford direct support for the view that glucokinase is indeed inhibited by endogenous long-chain fatty acyl-CoA in islets from omega3-depleted rats, such an inhibition probably participating to the alteration of D-glucose catabolism prevailing in these islets., (Copyright 2007 John Wiley & Sons, Ltd.)

The bolus intravenous injection of a novel medium-chain triglyceride:fish oil emulsion to normal subjects was recently reported to enrich within 60 min the phospholipid content of leucocytes and platelets in long-chain polyunsaturated omega3 fatty acids. The present study, conducted in second generation omega3-depleted rats, aims at investigating whether such a procedure may also increase within 60 min the phospholipid content of omega3 fatty acids in cells located outwards of the bloodstream, in this case liver cells, and whether this coincides with correction of the perturbation in the liver triglyceride fatty acid content and profile otherwise prevailing in these rats. The results indicate that such is indeed the case and further suggest a cause-to-effect relationship between the two events.

Rats depleted of long-chain polyunsaturated n-3 fatty acids (n-3-D) display several features of the metabolic syndrome, including obesity, liver steatosis, insulin resistance, hypertension, and cardiac hypertrophy. In this study, the heart phospholipid (PL) and triacylglycerol (TG) fatty acid content and pattern were compared between female control rats (C) and n-3-D rats. The sole n-3 fatty acids found in n-3-D rats, C22:5(n-3) and C22:6(n-3), were 10 to 20 times lower than in C. The total fatty acid content of PL was lower in n-3-D rats than C. No ectopic TG accumulation was found in n-3-D rats. In both PL and TG, the C16:0/C16:1(n-7) and C18:0/C18:1(n-9) ratios suggested increased Delta9-desaturase activity in n-3-D rats. The PL C18:2(n-6)/C20:4(n-6) and C20:4(n-6)/C22:4(n-6) ratios were also lower in n-3-D rats than C. Prior intravenous injection of a medium-chain TG:fish oil emulsion to n-3-D rats 60 to 120 minutes before killing augmented the PL content in C22:5(n-3) and C22:6(n-3), minimized the age-related decrease in the PL C18:1(n-9) relative content, and increased the TG C22:4(n-6) content. The alteration of cardiac function in n-3-D rats and its improvement after injection of medium-chain TG:fish oil emulsion coincides with parallel changes in heart lipid fatty acid content and pattern.

The catabolism of D-glucose was recently found to be impaired in pancreatic islets from rats depleted in long-chain polyunsaturated omega3 fatty acids. The specificity of this alteration was now investigated by characterizing the oxidative fate of endogenous nutrients in islets preincubated with either L-[U-14C]glutamine or [U-14C]palmitate and then incubated variously in the absence of D-glucose, presence of the hexose or presence of metabolic poisons. Relative to their radioactive content after preincubation, the production of 14CO2 by islets prelabelled with [U-14C]glutamine was higher in omega3-depleted rats than control animals. The enhancing action of D-glucose upon such production was impaired, however, in the omega3-depleted rats. The net uptake of 14C-palmitate and absolute value for 14CO2 output were both increased in omega3-depleted rats, whilst the ratio between 14CO2 output and islet radioactive content was decreased in the same animals. The inhibition of 14CO2 production by metabolic poisons was comparable in all cases. These results are consistent with recent findings on such items as the availability of endogenous amino acids and uptake of unesterified fatty acids in extrapancreatic sites of the omega3-depleted rats. They also support the view that the alteration of D-glucose metabolism in the islets of the latter animals may be attributable, in part at least, to alteration of glucokinase kinetics by high intracellular acyl-CoA levels., (2007 John Wiley & Sons, Ltd.)

The bolus intravenous injection of a novel medium-chain triglyceride:fish oil (FO) emulsion was recently proposed as a tool to provoke a rapid enrichment of cell phospholipids in long-chain polyunsaturated omega-3 fatty acids. In the present study, the enrichment of liver phospholipids and triglycerides in C20:5omega-3, C22:5omega-3 and C22:6omega-3 was assessed 60min after the intravenous administration of FO (1.0ml) to second-generation omega-3-depleted rats. When compared to uninjected rats, or animals injected with a control omega-3 fatty acid-poor medium-chain triglyceride:olive oil (OO) emulsion, the enrichment of liver phospholipids, and to a lesser extent liver triglycerides, attributable to the injection of the FO emulsion was more pronounced for C22:6omega-3 than C20:5omega-3, despite the presence of equal amounts of these two omega-3 fatty acids in the injected diglycerides and triglycerides. The possible determinants and potential beneficial effects of such a difference are briefly discussed.

Rats depleted in long-chain polyunsaturated omega3 fatty acids (omega3-depleted rats) display several features of the metabolic syndrome including hypertension and cardiac hypertrophy. This coincides with alteration of the cardiac muscle phospholipid and triacylglycerol fatty acid content and/or pattern. In the present study, the latter variables were measured in the cardiac endothelium of normal and omega3-depleted rats. Samples derived from four rats each were obtained from 16 female normal fed rats and three groups of 36-40 female fed omega3-depleted rats each aged 8-9, 15-16 and 22-23 weeks. At comparable mean age, the ratio between the square root of the total fatty acid content of phospholipids and cubic root of the total fatty acid content of triacylglycerols was lower in omega3-depleted rats than in control animals. The total fatty acid content of triacylglycerols was inversely related to their relative content in C20:4omega6. Other differences between omega3-depleted rats and control animals consisted in a lower content of long-chain polyunsaturated omega3 fatty acids in both phospholipids and triacylglycerols, higher content of long-chain polyunsaturated omega6 fatty acids in phospholipids, higher activity of delta9-desaturase (C16:0/C16:1omega7 and C18:0/C18:1omega9 ratios) and elongase [(C16:0 + C16:1omega7)/(C18:0 + C18:1omega9) and C20:4omega6/C22:4omega6 ratios], but impaired generation of C22:6omega3 from C22:5omega3 in the former rats. These findings support the view that cardiovascular perturbations previously documented in the omega3-depleted rats may involve impaired heart endothelial function., (2007 John Wiley & Sons, Ltd.)