Fatty acid profile of plasma and liver lipids in mice depleted in long-chain polyunsaturated (n-3) 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.     

Correlation between liver and plasma fatty acid profile of phospholipids and triglycerides in rats

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.     

Spontaneously hypertensive and Wistar Kyoto rats differ in delayed matching-to-place performance and response to dietary long-chain polyunsaturated fatty acids

Spontaneously hypertensive rats (SHR) were used as an animal model of attention deficit hyperactivity disorder (ADHD). This study investigated whether, in comparison with its progenitor strain, Wistar-Kyoto rats (WKY), SHR would show deficits in spatial short-term memory in the delayed-matching-to-place (DMP) version of the Morris water maze and be more distracted by exposure to a novel stimulus during recall trials. It also addressed whether dietary supplementation with long-chain polyunsaturated fatty acids (LCPUFA) during development would increase brain docosahexaenoic acid (DHA) and improve SHR behavioral performance. Beginning at weaning (21 days), male SHR and WKY were fed either a control or LCPUFA supplemented diet [0.5% arachidonic acid (AA) and 0.9% DHA], and behavioral testing began at 8 weeks. The first three tasks comprised a series of problems, each consisting of an initial search trial and subsequent recall trials. The intertrial interval (ITI) between the search and recall trial was either 60 s or 60 min. Surprisingly, in contrast to SHR, WKY did not appear to use a spatial short-term memory strategy to solve the problem. Notwithstanding, the performance of both strains was affected by the delay, such that they showed longer path lengths at the long compared with the short ITI. There was no effect of dietary supplementation on DMP performance. SHR fed the control diet were less responsive to a novel stimulus introduced on the first recall trial than WKY, and this tended to increase with supplementation. Analysis of brain fatty acid composition indicated that supplementation did increase DHA in the phosphatidylethanolamine fraction in WKY; however, in SHR, there was either no change (phosphatidylethanolamine) or paradoxical decreases (phosphatidylcholine and phosphatidyserine/phosphatidylinositol). Further research is needed to determine whether SHR are an appropriate model for studying a possible relationship between dietary LCPUFA and the behavioral symptoms of ADHD.     

The orosensory recognition of long-chain fatty acids in rats.

To determine the selectivity of long-chain fatty acid (LCFA) in the oral cavity, short-term (5 min) two-bottle tests were conducted in rats. Fifteen male Wistar rats were given oleic acid, linoleic acid, linolenic acid, and their derivatives. All compounds used were 99% pure. The concentration of test fluids was made 1% in 0.3% xanthan gum to minimize postingestive and textural effects. The rats preferred LCFA fluids to the control of 0.3% xanthan gum solution. The preference order of LCFA was linolenic acid > linoleic acid > oleic acid. Four LCFA derivatives (methyl oleate, oleyl alcohol, methyl linoleate, and linolyl alcohol), triolein, and capric acid were not preferred to LCFA, but LCFA derivatives were preferred to the control of xanthan gum solution. These studies suggest that rats select LCFA from olfactory or gustatory cues that are related to both the carbon chain and carboxylate group.     

Utilization of long-chain fatty acids in human skeletal muscle during exercise

Long-chain fatty acids (LCFA) are important sources of energy in contracting skeletal muscle: during the course of endurance exercise the contribution of LCFA in energy metabolism increases whereas when the intensity of exercise increases, the energy need is covered more and more by carbohydrates. Although this has been known for nearly 100 years, the mechanisms controlling fatty acid uptake and oxidation during various exercise modes are still not completely elucidated. Besides passive diffusion, data suggest that both membrane-associated and cytosolic fatty acid binding proteins are involved in the uptake of LCFA into skeletal muscle. However, data from human studies suggest that the regulation of fatty acid utilization in skeletal muscle during exercise lies mainly within the entrance into the mitochondria or metabolism within the mitochondria. Although possible compartmentalization within the cell makes definitive conclusions difficult, available evidence suggests that changes in malonyl CoA concentration in muscle do not play a major regulatory role in controlling LCFA oxidation during exercise in man. In contrast, it is suggested that the availability of free carnitine may play a major regulatory role in oxidation of LCFA during exercise.     

Rapid changes in liver lipid composition and pancreatic islet K+ handling and secretory behaviour provoked by the intravenous administration of a medium-chain triglyceride: fish oil emulsion to long-chain polyunsaturated omega3 fatty acid-depleted rats

Second generation rats depleted in long-chain polyunsaturated omega3 fatty acids are currently used as an animal model for the insufficient dietary supply of such fatty acids often prevailing in Western populations. The present study deals mainly with the effects of a novel medium-chain triglyceride: fish oil emulsion (MCT:FO), as compared to a control medium-chain triglyceride:olive oil emulsion (MCT: OO), administered as an intravenous bolus to the omega3-depleted rats 60-120 min before sacrifice upon selected biochemical and biophysical variables. The major findings consisted of a severe decrease of the omega3 fatty acid content of liver lipids in non-injected omega3-depleted rats and its partial correction after injection of the MCT:FO emulsion. The omega3-depleted rats also displayed liver steatosis, increased incorporation of long-chain polyunsaturated omega6 fatty acids in liver phospholipids and increased activity of liver Delta9-desaturase. As judged from the effects of ouabain upon 86Rb net uptake by isolated pancreatic islets, the activity of Na+,K+-ATPase was virtually abolished in the omega3-depleted rats. The latter defect was corrected by prior intravenous injection of the MCT:FO emulsion, this coinciding with suppression of the excessive secretory response to a number of insulin secretagogues otherwise observed in the islets of omega3-depleted rats injected or not with the MCT:OO emulsion.     

Age-related changes of long-chain fatty acid metabolism in rat liver

Palmitate oxidation activity and the activities of several enzymes involved in long-chain fatty acid metabolism were examined in the liver of young adult (2-month-old) and senescent (32-month-old) female rats. Palmitate oxidation activity in rat liver mitochondria showed age-related decrease, as judged by the rates of both 14CO2 production and formation of radioactive acid-soluble products from [1-14C]palmitate. In addition, long-chain acyl-coenzyme A synthetase activity was found to be decreased in liver mitochondria and increased in liver microsomes in senescent rats. These results suggest that, in the rat liver, preferential channeling of long-chain fatty acids through the triacylglycerol synthetic pathway may increase with age, and as a result, energy production by their oxidation may decrease.     

Fatty acid content and pattern of spleen phospholipids and triglycerides in normal and either type-1 or type-2 diabetic rats

The fatty acid pattern of spleen phospholipids and triglycerides was examined in fed or overnight fasted normal rats, streptozotocin-induced diabetic animals (type-1 diabetes) and Goto-Kakizaki rats (type-2 diabetes). In both phospholipids and triglycerides, differences were observed in the relative contribution of several fatty acids, as well as in the ratio between distinct fatty acids, when comparing fed to fasted rats, normal to diabetic animals and male to female Goto-Kakizaki rats. Diabetes increased to a greater extent the C22:6omega3 content of phospholipids in the spleen than in either the liver or the brain. However, the diabetes-induced changes in the C22:6omega3 content of triglycerides was closely comparable in the spleen, liver and brain. These findings suggest that the incorporation of fatty acids into triglycerides is controlled by comparable regulatory factor(s), e.g. insulinemia, in the spleen, liver and brain. In the case of phospholipids, however, an apparent adaptation to diabetic stress was more marked in the spleen than in the liver, and virtually absent in the brain. The proposed dichotomy in the environmental regulation of fatty acid synthesis and incorporation into phospholipids and triglycerides was further supported by distinct diabetes-related changes in the apparent activity of Delta9-desaturase in these two classes of lipids.     

Cardioprotective effects of omega 3 fatty acids: origin of the variability

Since 40 years, it is known that omega-3 poly-unsaturated fatty acids (ω3 PUFAs) have cardioprotective effects. These include antiarrhythmic effects, improvements of autonomic function, endothelial function, platelet anti-aggregation and inflammatory properties, lowering blood pressure, plaque stabilization and reduced atherosclerosis. However, recently, conflicting results regarding the health benefits of ω3 PUFAs from seafood or ω3 PUFAs supplements have emerged. The aim of this review is to examine recent literature regarding health aspects of ω3 PUFAs intake from fish or supplements, and to discuss different arguments/reasons supporting these conflicting findings.     

长链多不饱和脂肪酸与足月儿智能和精神运动发育关系的Meta分析

目的对添加长链多不饱和脂肪酸（LCPUFAs）配方奶喂养足月儿的智能和精神运动发育进行评价。方法使用相关的检索词检索Cochrane图书馆、PubMed、EMBASE、中国生物文献数据库和中文科技期刊全文数据库,获取添加LCPUFAs配方奶喂养的相关RCT文献,由2名评价者进行资料提取和文献质量评价,对同质资料运用RevMan4．3．2软件进行Meta分析。结果共6项研究（n=894）符合纳入标准进入Meta分析。根据随机方法、分配隐藏、盲法和随访情况评分,文献质量A级5篇,B级1篇。按年龄分为12月龄和18月龄亚组。Meta分析结果显示：①对智力发育指数的影响：12月龄亚组加权均数差值（WMD）：-1．66（95％CI：-4．09～0．76,P=0．18）,18月龄亚组WMD=-0．70（95％CI：-2．90～1．51,P=0．54）,两亚组合并分析,合并WMD=-1．13（95％CI：-2．76～0．50,P=0．17）;②对精神运动发育指数的影响：12月龄亚组WMD=-1．14（95％CI：-4．39～2．12,P=0．49）,18月龄亚组WMD=0．70（95％CI：-0．88～2．27,P=0．39）,两亚组合并分析：合并WMD=0．35（95％CI：-1．07～1．77,P=0．63）。提示添加LCPUFAs配方奶喂养足月儿的智力发育指数和精神运动发育指数与未添加LCPUFAs配方奶组的差异均无统计学意义。结论现有的证据显示,添加LCPUFAs的配方奶对足月儿智能及精神运动发育无积极或消极影响。     

Protein kinase A is activated by the n–3 polyunsaturated fatty acid eicosapentaenoic acid in rat ventricular muscle

During cardiac ischaemia antiarrhythmic n –3 polyunsaturated fatty acids (PUFAs) are released following activation of phospholipase A2, if they are in the diet prior to ischaemia. Here we show a positive lusitropic effect of one such PUFA, eicosapentaenoic acid (EPA) in the antiarrhythmic concentration range in Langendorff hearts and isolated rat ventricular myocytes due to activation of protein kinase A (PKA). Several different approaches indicated activation of PKA by EPA (5–10 μmol l⁻¹): the time constant of decay of the systolic Ca²+ transient decreased to 65.3 ± 5.0% of control, Western blot analysis showed a fourfold increase in phospholamban phosphorylation, and PKA activity increased by 21.0 ± 7.3%. In addition myofilament Ca²+ sensitivity was reduced in EPA; this too may have resulted from PKA activation. We also found that EPA inhibited L-type Ca²+ current by 38.7 ± 3.9% but this increased to 63.3 ± 3.4% in 10 μmol l⁻¹ H89 (to inhibit PKA), providing further evidence of activation of PKA by EPA. PKA inhibition also prevented the lusitropic effect of EPA on the systolic Ca²+ transient and contraction. Our measurements show, however, PKA activation in EPA cannot be explained by increased cAMP levels and alternative mechanisms for PKA activation are discussed. The combined lusitropic effect and inhibition of contraction by EPA may, respectively, combat diastolic dysfunction in ischaemic cardiac muscle and promote cell survival by preserving ATP. This is a further level of protection for the heart in addition to the well-documented antiarrhythmic qualities of these fatty acids.     

Effects of dietary supplementation with n-6 and n-3 long-chain polyunsaturated fatty acids on serum lipoproteins and platelet function in hypertriglyceridaemic patients

Twenty-seven patients with hypertriglyceridaemia were given dietary supplementation either with evening primrose oil rich in gammalinolenic acid (GLA, 18:3 n-6) (n = 13) or a marine oil concentrate containing n-3 fatty acids (n = 14) in a double-blind cross-over design during 8 + 8 weeks with olive oil as placebo. During GLA supplementation, increases in GLA and dihomogammalinolenic acid (20:3 n-6) were found in plasma lipid esters and platelet phospholipids, whereas platelet function and serum lipoproteins were unaffected. During supplementation with n-3 fatty acids there was a significant decrease in triglycerides in all lipoprotein fractions with a slight increase in high density lipoprotein and low density lipoprotein cholesterol. A marked increase in the long-chain n-3 fatty acids was found both in plasma and platelets, mainly at the expense of the n-6 fatty acids. No pronounced effects on platelet reactivity could be demonstrated. Our results confirm a triglyceride-lowering effect of n-3 fatty acids, whereas no such effect of GLA could be demonstrated.     

Treatment with Mesna and n‐3 polyunsaturated fatty acids ameliorates experimental ulcerative colitis in rats

Oxidative damage is a central feature of ulcerative colitis. Here, we tested whether the antioxidant Mesna, when administered alone or in combination with n‐3 polyunsaturated fatty acids (n‐3 PUFAs), affects the outcome of dextran sodium sulphate (DSS)‐induced ulcerative colitis in rats. After the induction of colitis, DSS‐treated rats were further treated orally (p.o), intraperitoneally (i.p) or intrarectally (i.r) for either 7 or 14 days with Mesna, n‐3 PUFAs or both. Rats were euthanized at the end of each treatment period. Clinical disease activity index was recorded throughout the experiment. At necropsy colorectal gross lesions were scored. Colitis was scored histologically, and the expression of myeloperoxidase (MPO), caspase‐3, inducible nitric oxide synthase (iNOS) and nuclear factor κB (NF‐κΒ) in colonic tissue was assessed by immunohistochemistry. Mesna alone was sufficient to significantly reduce colorectal tissue damage when administered orally or intraperitoneally. Orally coadministered n‐3 PUFAs enhanced this effect, resulting in the significant suppression of DSS colitis after 7 days, and a remarkable recovery of colorectal mucosa was evident after 14 days of treatment. The amelioration of colon pathology co‐existed with a significant decrease in MPO expression, overexpression of iNOS and reduction of nuclear NF‐κB p65 in inflammatory cells, and the suppression of apoptosis in colonic epithelial cells. The simultaneous administration of Mesna and n‐3 PUFAs is particularly effective in ameliorating DSS colitis in rats, by reducing oxidative stress, inflammation and apoptosis, probably through a mechanism that involves the inhibition of NF‐κB and overexpression of iNOS.     

The role of omega 3 fatty acids on insulin secretion and insulin sensitivity

Carbohydrate intolerance is positively correlated with animal fat consumption and is more common in beef eating populations. In contrast, individuals consuming diets comprised of polyunsaturated fats have a lower incidence of diabetes mellitus. This is especially apparent in the Eskimos living in Alaska and Greenland whose diet is highly enriched with omega 3 fatty acids. It is hypothesized that dietary enrichment with omega 3 fatty acids increases the incorporation of these fatty acids into the beta cell phospholipid membrane thus enhancing insulin secretion. It is also proposed that similar changes occur in the phospholipid membrane composition of peripheral cells. These changes in the membrane phospholipids would then theoretically increase both insulin receptor binding affinity and sensitivity, thus enhancing glucose transport across their membranes. Augmented insulin secretion and increased insulin sensitivity induced by chronic omega 3 fatty acid ingestion would positively influence carbohydrate metabolism and improve glucose homeostasis.     

Palmitic acid metabolism in the soleus muscle in vitro in hypo- and hyperthyroid rats

The aim of this study was to establish whether the rate of fatty acid (FA) incorporation and its utilization by the isolated soleus muscle is modified under conditions of thyroid hormone deficit or excess. The rate of palmitic acid (PA) uptake, oxidation and incorporation into intramuscular lipids with increasing PA concentration (0.5–1.5 mM) in the incubation medium were determined. In hypothyroid rats intramuscular triacylglycerol (TG) synthesis was increased, while the rate of PA oxidation to CO₂ and incorporation into mono- and diacylglycerols (MG/DG) and phospholipids (PL) remained unchanged. In rats with triiodothyronine (T₃) excess the rate of all processes studied was enhanced, although the percentage incorporation of PA into different classes of intramuscular lipids was fairly constant and, independently of thyroid state and FA concentration in the medium, was 56–66% for TG, 9-14% for MG/DG and 24–32% for PL. Our results thus indicate that even short-term T₃ excess accelerates the rate of FA uptake and metabolism in the oxidative soleus muscle, whereas in hypothyroid rats only intramuscular TG synthesis is affected.     

Hydroxyeicosapentaenoic acids and epoxyeicosatetraenoic acids derived from n3 polyunsaturated fatty acid attenuate early occurrence of nonalcoholic fatty liver disease: targeted metabolomics-based research

<正>High-fat diet(HFD)treatment as little as 3 d induced fatty liver,insulin resistance and adipose inflammation.n3 PUFAs and their metabolites eicosanoids mediate protective effects on several metabolic disorders.However,the functions of n3 PUFA metabolites are largely unknown.Early in the course of HFD feeding for 4 d,we found significant lipid accumulation in mouse liver which was re-