Tetradecylthioacetic Acid Increases Fat Metabolism and Improves Cardiac Function in Experimental Heart Failure

Changes in myocardial metabolism, including a shift from fatty acid to glucose utilization and changes in fatty acid availability and composition are characteristics of heart failure development. Tetradecylthioacetic acid (TTA) is a fatty acid analogue lacking the ability to undergo mitochondrial β-oxidation. TTA promotes hepatic proliferation of mitochondria and peroxisomes and also decreases serum triglycerides and cholesterol in animals. We investigated the effect of TTA, in combination with a high-fat or regular diet, in a rat model of post-myocardial infarction heart failure. TTA had a beneficial effect on cardiac function in post-myocardial infarction heart failure without affecting myocardial remodeling. These effects of TTA on myocardial function were accompanied by decreased free fatty acids in plasma, increased myocardial proportion of n-3 polyunsaturated fatty acids (PUFA) and a decreased proportion of n-6 PUFA. Myocardial enzyme gene expression during TTA treatment suggested that the increase in n-3 PUFA could reflect increased n-3 PUFA synthesis and inadequately increased n-3 PUFA β-oxidation. Based on our data, it is unlikely that the changes are secondary to alterations in other tissues as plasma and liver showed an opposite pattern with decreased n-3 PUFA during TTA treatment. The present study suggests that TTA may improve myocardial function in heart failure, potentially involving its ability to decrease the availability of FFA and increase the myocardial proportion of n-3 PUFA.     

Essentiality of fatty acids

All fatty acids have important functions, but the term “essential” is applied only to those polyunsaturated fatty acids (PUFA) that are necessary for good health and cannot be completely synthesized in the body. The need for arachidonic acid, which is utilized for eicosanoid synthesis and is a constituent of membrane phospholipids involved in signal transduction, is the main reason why the n-6 class of PUFA are essential. Physiological data indicate that n-3 PUFA also are essential. Although eicosapentaenoic acid also is a substrate for eicosanoid synthesis, docosahexaenoic acid (DHA) is more likely to be the essential n-3 constituent because it is necessary for optimal visual acuity and neural development. DHA is present in large amounts in the ethanolamine and serine phospholipids, suggesting that its function involves membrane structure. Because the metabolism of n-6 PUFA is geared primarily to produce arachidonic acid, only small amounts of 22-carbon n-6 PUFA are ordinarily formed. Thus, the essentiality of n-3 PUFA may be due to their ability to supply enough 22-carbon PUFA for optimal membrane function rather than to a unique biochemical property of DHA.     

Interlaboratory Assessment of Dried Blood Spot Fatty Acid Compositions

Dried blood spots for fatty acid profiling are increasing in popularity; however, variability in results between laboratories has not been characterized. Whole blood from two subjects (low and high n-3 polyunsaturated fatty acid [PUFA] status) was collected, 25 μL applied to butylated hydroxytoluene (BHT)-treated chromatography strips, dried in air, and shipped to five laboratories. Results were reported as “routine” (typical fatty acids for each laboratory) or “standardized” (a set of 19 fatty acids), and outliers and variability (%CV) were determined. Five and eight outliers of a possible 91 measures each were identified by routine and standardized reporting, respectively, including eicosapentaenoic acid (EPA, 20:5n-3) in the low n-3 PUFA sample and arachidonic acid in the high n-3 PUFA sample. By standardized reporting, no outliers were identified for EPA or docosahexaenoic acid (DHA, 22:6n-3), and %CV decreased from 8.6% to 6.0% and 9.1% to 6.6% for EPA and 10.5% to 7.2% and 10.5% to 6.6% for DHA in the low and high n-3 PUFA sample, respectively. In conclusion, fatty acid profiles yielded few outliers, and standardization of reporting reduced the variability between laboratories.     

Contrasting Effects of n-3 and n-6 Fatty Acids on Cyclooxygenase-2 in Model Systems for Arthritis

Cyclooxygenase-2 (COX-2) is intimately involved in symptoms of arthritis while dietary n-3 polyunsaturated fatty acids (PUFA) are thought to be beneficial. In these experiments, using both bovine and human in vitro systems that mimic features of arthritis, we show that the n-3 PUFA eicosapentaenoic acid (EPA) is able to reduce mRNA and protein levels of COX-2. Activity, as assessed through prostaglandin E₂ formation, was also reduced in a dose-dependent manner. These effects of EPA contrasted noticeably with the n-6 PUFA, arachidonic acid. The data provide direct evidence for a molecular mechanism by which dietary n-3 PUFA, such as EPA, can reduce inflammation and, hence, associated symptoms in arthritis.     

The metabolism and n−6/n−3 ratio of essential fatty acids in rats: Effect of dietary arachidonic acid and a mixture of sesame lignans (sesamin and episesamin)

In this study, we examined the effect of dietary arachidonic acid (AA) and sesame lignans on the content and n-6/n-3 ratio of polyunsaturated fatty acid (PUFA) in rat liver and the concentrations of triglyceride (TG) and ketone bodies in serum. For 4 wk, rats were fed two types of dietary oils: (i) the control oil diet groups (CO and COS): soybean oil/perilla oil=5∶1, and (ii) the AA-rich oil group (AO and AOS): AA ethyl esters/palm oil/perilla oil=2∶∶1, with (COS and AOS) or without (CO and AO) 0.5% (w/w) of sesame lignans. Dietary AA and sesame lignans significantly affected hepatic PUFA metabolism. AA content and n-6/n-3 ratio in the liver were significantly increased in the AO group, despite the dietary total of n-6 PUFA being the same in all groups, while AOS diet reduced AA content and n-6/n-3 ratio to a level similar to the CO and COS groups. These results suggest that (i) dietary AA considerably affects the hepatic profile and n-6/n-3 ratio of PUFA, and (ii) dietary sesame lignans reduce AA content and n-6/n-3 ratio in the liver. In the AO group, the concentration of acetoacetate was significantly increased, but the ratio of β-hydroxybutyrate/acetoacetate was decreased. On the other hand, the AO diet increased the concentration of TG in serum by almost twofold as compared to other groups. However, the AOS diet significantly reduced serum IG level as compared to the AO group. In addition, the AOS diet signicantly increased the acetoacetate level, but reduced the β-hydroxybutyrate/acetoacetate ratio. These results suggest that dietary sesame lignans promote ketogenesis and reduce PUFA esterification into TG. This study resulted in two findings: (i) sesame lignans inhibited extreme changes of the n-6/n-3 ratio by reducing hepatic PUFA content, and (ii) the reduction of hepatic PUFA content may have occurred because of the effects of sesame lignans on PUFA degradation (oxidation) and esterification.     

Susceptibility of Female Mice to the Dietary Omega-3/Omega-6 Fatty-Acid Ratio: Effects on Adult Hippocampal Neurogenesis and Glia

Maternal intake of omega-3 (n-3 PUFAs) and omega-6 (n-6 PUFAs) polyunsaturated fatty acids impacts hippocampal neurogenesis during development, an effect that may extend to adulthood by altering adult hippocampal neurogenesis (AHN). The n-3 PUFAs and n-6 PUFAs are precursors of inflammatory regulators that potentially affect AHN and glia. Additionally, n-3 PUFA dietary supplementation may present a sexually dimorphic action in the brain. Therefore, we postulated that dietary n-6/n-3 PUFA balance shapes the adult DG in a sex-dependent manner influencing AHN and glia. We test our hypothesis by feeding adult female and male mice with n-3 PUFA balanced or deficient diets. To analyze the immunomodulatory potential of the diets, we injected mice with the bacterial endotoxin lipopolysaccharide (LPS). LPS reduced neuroblast number, and its effect was exacerbated by the n-3 PUFA-deficient diet. The n-3 PUFA-deficient diet reduced the DG volume, AHN, microglia number, and surveilled volume. The diet effect on most mature neuroblasts was exclusively significant in female mice. Colocalization and multivariate analysis revealed an association between microglia and AHN, as well as the sexual dimorphic effect of diet. Our study reveals that female mice are more susceptible than males to the effect of dietary n-6/n-3 PUFA ratio on AHN and microglia.     

Accretion of Dietary Docosahexaenoic Acid in Mouse Tissues Did Not Differ between Its Purified Phospholipid and Triacylglycerol Forms

Recent studies suggest that dietary krill oil leads to higher omega-3 polyunsaturated fatty acids (n-3 PUFA) tissue accretion compared to fish oil because the former is rich in n-3 PUFA esterified as phospholipids (PL), while n-3 PUFA in fish oil are primarily esterified as triacylglycerols (TAG). Tissue accretion of the same dietary concentrations of PL- and TAG-docosahexaenoic acid (22:6n-3) (DHA) has not been compared and was the focus of this study. Mice (n = 12/group) were fed either a control diet or one of six DHA (1%, 2%, or 4%) as PL-DHA or TAG-DHA diets for 4 weeks. Compared with the control, DHA concentration in liver, adipose tissue (AT), heart, and eye, but not brain, were significantly higher in mice consuming either PL- or TAG-DHA, but there was no difference in DHA concentration in all tissues between the PL- or TAG-DHA forms. Consumption of PL- and TAG-DHA at all concentrations significantly elevated eicosapentaenoic acid (20:5n-3) (EPA) in all tissues when compared with the control group, while docoshexapentaenoic acid (22:5n-6) (DPA) was significantly higher in all tissues except for the eye and heart. Both DHA forms lowered total omega-6 polyunsaturated fatty acids (n-6 PUFA) in all tissues and total monounsaturated fatty acids (MUFA) in the liver and AT; total saturated fatty acid (SFA) were lowered in the liver but elevated in the AT. An increase in the DHA dose, independent of DHA forms, significantly lowered n-6 PUFA and significantly elevated n-3 PUFA concentration in all tissues. Our results do not support the claim that the PL form of n-3 PUFA leads to higher n-3 PUFA tissue accretion than their TAG form.     

Decreased Tissue Omega-6/Omega-3 Fatty Acid Ratio Prevents Chemotherapy-Induced Gastrointestinal Toxicity Associated with Alterations of Gut Microbiome

Gastrointestinal toxicity (GIT) is a debilitating side effect of Irinotecan (CPT-11) and limits its clinical utility. Gut dysbiosis has been shown to mediate this side effect of CPT-11 by increasing gut bacterial β-glucuronidase (GUSB) activity and impairing the intestinal mucosal barrier (IMB). We have recently shown the opposing effects of omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) on the gut microbiome. We hypothesized that elevated levels of tissue n-3 PUFA with a decreased n-6/n-3 PUFA ratio would reduce CPT-11-induced GIT and associated changes in the gut microbiome. Using a unique transgenic mouse (FAT-1) model combined with dietary supplementation experiments, we demonstrate that an elevated tissue n-3 PUFA status with a decreased n-6/n-3 PUFA ratio significantly reduces CPT-11-induced weight loss, bloody diarrhea, gut pathological changes, and mortality. Gut microbiome analysis by 16S rRNA gene sequencing and QIIME2 revealed that improvements in GIT were associated with the reduction in the CPT-11-induced increase in both GUSB-producing bacteria (e.g., Enterobacteriaceae) and GUSB enzyme activity, decrease in IMB-maintaining bacteria (e.g., Bifidobacterium), IMB dysfunction and systemic endotoxemia. These results uncover a host–microbiome interaction approach to the management of drug-induced gut toxicity. The prevention of CPT-11-induced gut microbiome changes by decreasing the tissue n-6/n-3 PUFA ratio could be a novel strategy to prevent chemotherapy-induced GIT.     

The hypotriglyceridemic effect of dietary n−3 FA is associated with increased β-oxidation and reduced leptin expression

To study the mechanisms responsible for the hypotriglyceridemic effect of marine oils, we monitored the effects of high dietary intake of n-3 PUFA on hepatic and muscular beta-oxidation, plasma leptin concentration, leptin receptor gene expression, and in vivo insulin action. Two groups of male Wistar rats were fed either a high-fat diet [28% (w/w) of saturated fat] or a high-fat diet containing 10% n-3 PUFA and 18% saturated fat for 3 wk. The hypotriglyceridemic effect of n-3 PUFA was accompanied by increased hepatic oxidation of palmitoyl-CoA (125%, P < 0.005) and palmitoyl-L-carnitine (480%, P < 0.005). These findings were corroborated by raised carnitine palmitoyltransferase-2 activity (154%, P < 0.001) and mRNA levels (91%, P < 0.01) as well as by simultaneous elevation of hepatic peroxisomal acyl-CoA oxidase activity (144%, P < 0.01) and mRNA content (82%, P < 0.05). In contrast, hepatic carnitine palmitoyltransferase-1 activity remained unchanged despite a twofold increased mRNA level after n-3 PUFA feeding. Skeletal muscle FA oxidation was less affected by dietary n-3 PUFA, and the stimulatory effect was found only in peroxisomes. Dietary intake of n-3 PUFA was followed by increased acyl-CoA oxidase activity (48%, P < 0.05) and mRNA level (83%, P < 0.05) in skeletal muscle. The increased FA oxidation after n-3 PUFA supplementation of the high-fat diet was accompanied by lower plasma leptin concentration (-38%, P < 0.05) and leptin mRNA expression (-66%, P < 0.05) in retroperitoneal adipose tissue, and elevated hepatic mRNA level for the leptin receptor Ob-Ra (140%, P < 0.05). Supplementation of the high-fat diet with n-3 PUFA enhanced in vivo insulin sensitivity, as shown by normalization of the glucose infusion rate during euglycemic hyperinsulinemic clamp. Our results indicate that the hypotriglyceridemic effect of dietary n-3 PUFA is associated with stimulation of FA oxidation in the liver and to a smaller extent in skeletal muscle. This may ameliorate dyslipidemia, tissue lipid accumulation, and insulin action, in spite of decreased plasma leptin level and leptin mRNA in adipose tissue.     

The cardiac antiarrhythmic effects of polyunsaturated fatty acid

Each year in the United States alone some 250,000 persons die within one hour of an acute myocardial infarction. These deaths are largely due to ischemia-induced ventricular arrhythmias, primarily ventricular fibrillation (VF). Thus a safe, simple means of preventing such arrhythmias has considerable public health benefit potential. We have demonstrated that the intravenous infusion of n-3 polyunsaturated fatty acids (PUFA) from fish oils will prevent ischemia-induced VF in prepared, nonanesthetized, exercising dogs, confirming earlier feeding studies in rats. We show that this protective effect is due to an action of the free acidic form of the PUFA to alter the electrophysiology of individual cardiac myocyte so that the cells are electrically more stable. The electrophysiologic effects, in turn, result from direct and specific effects of the PUFA to block the fast voltage-dependent sodium channels. The binding of the free fatty acids is directly to the protein of the sodium channels and results in prolongation of the inactivated state of these channels. Other ion channels are also affected by the PUFA. Two clinical trials with n-3 PUFA are mentioned which inadvertently support the antiarrhythmic potential of PUFA ingestion.     

A new relationship between total/high density lipoprotein cholesterol and polyunsaturated fatty acids

Dietary and plasma fatty acids have been linked to total cholesterol but not to the ratio of total/high-density lipoprotein cholesterol (TC/HDLC). To evaluate the relationship between dietary and plasma levels of polyunsaturated fatty acids (PUFA) and TC/HDLC, we analyzed cross-sectional and longitudinal data using 519 plasma samples (50% men, 50% women) from subjects participating in the Framingham Heart Study and results from a study feeding diets rich in either n-6 linoleic acid or n-3 α-linolenic acid with or without fish oil supplements (n-3 derivatives). Values of TC/HDLC are inversely related to the percent of plasma PUFA when both variables are measured at the same time in different subjects,R=0.82,P<0.000001. PUFA in phospholipids increase in response to increased dietary intake of different PUFA, either n-3 or n-6 or fish oils. There was a highly significant inverse relationship between TC/HDLC and the percent of PUFA in phospholipids,R=0.97,P<0.001. The relationship was similar regardless of the source and type of dietary fatty acids. A similar relationship existed when only the baseline points were considered. When plasma PUFA % increases, either in response to a diet high in PUFA or across different subjects, TC/HDLC ratios decline. Evaluation of plasma fatty acid profiles and increased balanced dietary intake of PUFA to bring fatty acid profiles of subjects with low PUFA plasma levels closer to the profile of a healthy reference group is an effective approach to reduce high TC/HDLC. Reductions of more than 50% in TC/HDLC appear feasible with dietary modification alone. Further research into fatty acid metabolic activity may determine the biochemical basis of common dysplipidemias.     

n-3 Polyunsaturated fatty acid-induced changes in the molecular species composition of diradylglycerol in murine peritoneal macrophages remain stable during incubationex vivo

Three- to four-week-old C57BL/6 mice were maintained for four weeks on diets in which the 10% lipid component was the ethyl esters of either corn oil or n-3 polyunsaturated fatty acids (n-3 PUFA). Incubation of macrophagesex vivo for 14 h, a normal incubation time used for macrophage studies, in the absence of fetal calf serum, did not diminish the extent of incorporation of 20∶5n-3 (eicosapentaenoic acid) and 22∶6n-3 (docosahexaenoic acid) moieties into membrane phospholipids and into diradylglycerol (DG) relative to that after a very abbreviated incubation time. We conclude that studies examining the effects of dietary n-3 PUFA on DG formation and related physiological effects in macrophages can be performed after a normalex vivo incubation of at least 14 h without experiencing a significant loss of incorporated n-3 PUFA.     

Important Differences Exist in the Dose–Response Relationship between Diet and Immune Cell Fatty Acids in Humans and Rodents

Omega-3 polyunsaturated fatty acids (n-3 PUFA) are noted for their ability to diminish inflammatory and immune responses in vitro and in a variety of animal-based models of autoimmunity and inflammation. Yet, recent systematic reviews suggest that the evidence for these fatty acids having beneficial effects on inflammation or autoimmunity in humans is equivocal. A possible explanation for these disappointing and somewhat paradoxical findings emerged from the analyses described in this review. The available data on the changes in immune cell fatty acid profiles in mice, rats and humans, fed various forms and amounts of n-3 PUFA are summarized and displayed graphically. The dose–response curves generated provide new insights into the relationship between dietary n-3 PUFA and immune cell fatty acid profiles. The author suggests that the poor predictive value of most in vitro as well as many animal trials may, in part, be a consequence of the frequent adoption of experimental conditions that create differences in immune cell fatty acid profiles that far exceed what is possible in free-living humans through dietary intervention. Recommendations for improving the preclinical value of future in vitro and animal-based studies with n-3 PUFA are provided.     

Comparative Effects of Sandalwood Seed Oil on Fatty Acid Profiles and Inflammatory Factors in Rats

The aim of the present study was to investigate the effect of sandalwood seed oil on fatty acid (FA) profiles and inflammatory factors in rats. Fifty male Sprague–Dawley rats were randomly divided into five different dietary groups: 10 % soybean oil (SO), 10 % olive oil (OO), 10 % safflower oil (SFO), 10 % linseed oil (LSO) and 8 % sandalwood seed oil blended with 2 % SO (SWSO) for 8 weeks. The SWSO group had a higher total n-3 polyunsaturated fatty acids (PUFA) levels but lower n-6:n-3 PUFA ratios in both adipose tissue and liver than those in the SO, OO and SFO groups (p < 0.05). Although the SWSO group had a much lower 18:3n-3 level (4.51 %) in their dietary lipids than the LSO group (58.88 %), the levels of docosahexaenoic acid (DHA: 22:6n-3) in liver lipids and phospholipids of the SWSO group (7.52 and 11.77 %) were comparable to those of the LSO group (7.07 and 13.16 %). Ximenynic acid, a predominant acetylenic FA in sandalwood seed oil, was found to be highly incorporated into adipose tissue (13.73 %), but relatively lower in liver (0.51 %) in the SWSO group. The levels of prostaglandin F_2α, prostaglandin E₂, thromboxane B₂, leukotriene B₄, tumor necrosis factor-α and interleukin-1β in both liver and plasma were positively correlated with the n-6:n-3 ratios, suggesting that increased n-6 PUFA appear to increase the formation of pro-inflammatory cytokines, whereas n-3 PUFA exhibit anti-inflammatory activity. The present results suggest that sandalwood seed oil could increase tissue levels of n-3 PUFA, DHA and reduce the n-6:n-3 ratio, and may increase the anti-inflammatory activity in rats.     

Restoration of depressed prostanoid-induced ileal contraction in spontaneously hypertensive rats by dietary fish oil

We have reported that dietary fish oil (FO) rich in n-3 PUFA modulates gut contractility. It was further demonstrated that the gut of spontaneously hypertensive rats (SHR) has a depressed contractility response to prostaglandins (PG) compared with normotensive Wistar-Kyoto (WKY) rats. We investigated whether feeding diets supplemented with n-3 PUFA increased gut contractility and restored the depressed prostanoid response in SHR gut. Thirteen-week-old SHR were fed diets containing fat at 5 g/100 g as coconut oil (CO), lard, canola oil containing 10% (w/w) n-3 FA as alpha-linolenic acid (1 8:3n-3), or FO (as HiDHA, 22:6n-3) for 12 wk. A control WKY group was fed 5 g/100 g CO in the diet. As confirmed, the SHR CO group had a significantly lower gut response to PGE2 and PGF2alpha compared with the WKY CO group. Feeding FO increased the maximal contraction response to acetylcholine in the ileum compared with all diets and in the colon compared with lard, and restored the depressed response to PGE2 and PGF2alpha in the ileum but not the colon of SHR. FO feeding also led to a significant increase in gut total phospholipid n-3 PUFA as DHA (22:6n-3) with lower n-6 PUFA as arachidonic acid (20:4n-6). Canola feeding led to a small increase in ileal EPA (20:5n-3) and DHA and in colonic DHA without affecting contractility. However, there was no change in ileal membrane muscarinic binding properties due to FO feeding. This report confirms that dietary FO increases muscarinic- and eicosanoid receptor-induced contractility in ileum and that the depressed prostanoid response in SHR ileum, but not colon, is restored by tissue incorporation of DHA as the active nutrient.     

Season and Cooking May Alter Fatty Acids Profile of Polar Lipids from Blue-Back Fish

Polar lipids (PoL) represent a new promising dietary approach in the prevention and treatment of many human diseases, due to their potential nutritional value and unique biophysical properties. This study investigates the effects of catching season and oven baking on the fatty acid profiles (FAP) of PoL in four species of blue-back fish widely present in the North Adriatic Sea: anchovy (Engraulis encrasicholus), sardine (Sardina pilchardus), sprat (Sprattus sprattus), and horse mackerel (Trachurus trachurus). PoL levels (427–652 mg/100 g flesh) varied among the four species, with no significant seasonal variations within species. FAP of raw fillets were particularly high in polyunsaturated fatty acid (PUFA), especially docosahexaenoic acid (DHA) and EPA; total PUFA was constant in all species throughout the year, while long-chain n-3 polyunsaturated fatty acid (n-3 PUFA) rose in spring (except in sprat), especially due to the contribution of DHA. The FAP response for PoL to oven baking was species-specific and, among n-3 PUFA, DHA exhibited the greatest heat resistance; the influence of oven baking on FAP was found to be correlated with the catching season, especially for anchovy and sardine, while sprat PoL were not affected by cooking processes. The four species analyzed in this study presented very low n-6/n-3 fatty acid ratios and highly favorable nutritional indices, emphasizing their PoL qualities and promoting their role in increasing human n-3 PUFA intake. The four species can be considered as superior sources of n-3 PUFA and can be employed as supplements in functional food manufacturing and in pharmaceutical and cosmetic industries.     

Dietary Long-Chain n-3 Polyunsaturated Fatty Acid Supplementation Alters Electrophysiological Properties in the Nucleus Accumbens and Emotional Behavior in Naïve and Chronically Stressed Mice

Long-chain (LC) n-3 polyunsaturated fatty acids (PUFAs) have drawn attention in the field of neuropsychiatric disorders, in particular depression. However, whether dietary supplementation with LC n-3 PUFA protects from the development of mood disorders is still a matter of debate. In the present study, we studied the effect of a two-month exposure to isocaloric diets containing n-3 PUFAs in the form of relatively short-chain (SC) (6% of rapeseed oil, enriched in α-linolenic acid (ALA)) or LC (6% of tuna oil, enriched in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) PUFAs on behavior and synaptic plasticity of mice submitted or not to a chronic social defeat stress (CSDS), previously reported to alter emotional and social behavior, as well as synaptic plasticity in the nucleus accumbens (NAc). First, fatty acid content and lipid metabolism gene expression were measured in the NAc of mice fed a SC (control) or LC n-3 (supplemented) PUFA diet. Our results indicate that LC n-3 supplementation significantly increased some n-3 PUFAs, while decreasing some n-6 PUFAs. Then, in another cohort, control and n-3 PUFA-supplemented mice were subjected to CSDS, and social and emotional behaviors were assessed, together with long-term depression plasticity in accumbal medium spiny neurons. Overall, mice fed with n-3 PUFA supplementation displayed an emotional behavior profile and electrophysiological properties of medium spiny neurons which was distinct from the ones displayed by mice fed with the control diet, and this, independently of CSDS. Using the social interaction index to discriminate resilient and susceptible mice in the CSDS groups, n-3 supplementation promoted resiliency. Altogether, our results pinpoint that exposure to a diet rich in LC n-3 PUFA, as compared to a diet rich in SC n-3 PUFA, influences the NAc fatty acid profile. In addition, electrophysiological properties and emotional behavior were altered in LC n-3 PUFA mice, independently of CSDS. Our results bring new insights about the effect of LC n-3 PUFA on emotional behavior and synaptic plasticity.     

Unusually High Levels of n-6 Polyunsaturated Fatty Acids in Whale Sharks and Reef Manta Rays

Fatty acid (FA) signature analysis has been increasingly used to assess dietary preferences and trophodynamics in marine animals. We investigated FA signatures of connective tissue of the whale shark Rhincodon typus and muscle tissue of the reef manta ray Manta alfredi. We found high levels of n-6 polyunsaturated fatty acids (PUFA), dominated by arachidonic acid (20:4n-6; 12–17 % of total FA), and comparatively lower levels of the essential n-3 PUFA—eicosapentaenoic acid (20:5n-3; ~1 %) and docosahexaenoic acid (22:6n-3; 3–10 %). Whale sharks and reef manta rays are regularly observed feeding on surface aggregations of coastal crustacean zooplankton during the day, which generally have FA profiles dominated by n-3 PUFA. The high levels of n-6 PUFA in both giant elasmobranchs raise new questions about the origin of their main food source.     

Modification of membrane fatty acid composition,eicosanoid production,and phospholipase a activity in Atlantic Salmon (Salmo salar) gill and kidney by dietary lipid

Atlantic salmon post-smolts were fed diets containing either fish oils (Fosol, FO and Marinol, MO) rich in long-chain n-3 polyunsaturated fatty acids (PUFA), or plant oils rich in 18:2n-6 (sunflower oil, SO) or 18:3n-3 (linseed oil, LO) for 12 wk. The major PUFA in individual phospholipids from gill and kidney were related to the dietary lipid intake. Levels of n-6 PUFA were highest while levels of n-3 PUFA were lowest in fish fed SO. Fish fed LO generally had lower levels of 20:4n-6 compared to the other treatments while fish fed SO generally had the highest levels of 20:4n-6. In all phospholipid classes except phosphatidylinositol (PI) 20:5n-3 was greatest in fish fed MO followed by FO, LO, and SO. In PI, 20:5n-3 was also highest in fish fed MO but those fed LO contained more 20:5n-3 than those fed FO. This resulted in the ratio of the eicosanoid precursors, 20:4n-6/20:5n-3, being significantly greater in fish fed SO, for all phospholipid classes, compared to fish fed the other three dietary oils. The activity of gill phospholipase A was greatest in fish fed FO and was lowest in fish fed SO. The concentration of PGF_3α was significantly increased in gill homogenates from fish fed MO compared to the other three treatments while PGF_2α was significantly increased in fish fed SO compared to those fed LO. The concentration of PGE₃ was significantly reduced in kidney homogenates from fish fed SO compared to the other three treatments while PGE₂ was significantly increased in fish fed SO compared to those fed either FO or LO.