Blood clearance kinetics and organ delivery of medium-chain triglyceride and fish oil-containing lipid emulsions: Comparing different animal species.

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.

Novel Approaches for Omega-3 Fatty Acid Therapeutics: Chronic Versus Acute Administration to Protect Heart, Brain, and Spinal Cord.

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.

In vivo handling and metabolism of lipid emulsions.

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.

Proceedings From FDA/A.S.P.E.N. Public Workshop: Clinical Trial Design for Intravenous Fat Emulsion Products, October 29, 2013.

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.

A combined natural supplement lowers LDL cholesterol in subjects with moderate untreated hypercholesterolemia: a randomized placebo-controlled trial.

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.

Prebiotic approach alleviates hepatic steatosis: implication of fatty acid oxidative and cholesterol synthesis pathways.

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.

Perturbation of glycerol metabolism in hepatocytes from n3-PUFA-depleted rats.

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.

Rapid enrichment of cell phospholipids in long-chain polyunsaturated ω-3 fatty acids after a bolus intravenous injection of a medium-chain triacylglycerol: fish oil emulsion in humans.

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.

Hepatic n-3 polyunsaturated fatty acid depletion promotes steatosis and insulin resistance in mice: genomic analysis of cellular targets.

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.

Involvement of gut microbial fermentation in the metabolic alterations occurring in n-3 polyunsaturated fatty acids-depleted mice.

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.

Seasons but not ethnicity influence urinary iodine concentrations in Belgian adults.

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.

Fatty acid pattern of pancreatic islet lipids in Goto-Kakizaki rats.

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.

Rapid cellular enrichment of eicosapentaenoate after a single intravenous injection of a novel medium-chain triacylglycerol:fish-oil emulsion in humans.

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.

Plasma phospholipid-mediated transfer of docosahexaenoic acid from liver to brain phospholipids in type 1 and type 2 diabetic rats.

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.

The metabolic syndrome of omega3-depleted rats. VI. Intestinal phospholipid saturated and monodesaturated fatty acids.

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.

The metabolic syndrome of omega3-depleted rats. IV. Intestinal phospholipid omega3 fatty acids.

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 metabolic syndrome of omega3-depleted rats. V. Intestinal phospholipid omega6 fatty acids.

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.

Alteration of lipid fatty acid profile and cationic fluxes in ventricular cardiomyocytes from omega3-depleted rats.

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.

The metabolic syndrome of omega3-depleted rats. III. Brain phospholipids.

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.