Dietary polyunsaturated fatty acids increase survival and decrease bacterial load during septic Staphylococcus aureus infection and improve neutrophil function in mice.

Severe infection, including sepsis, is an increasing clinical problem that causes prolonged morbidity and substantial mortality. At present, antibiotics are essentially the only pharmacological treatment for sepsis. The incidence of resistance to antibiotics is increasing; therefore, it is critical to find new therapies for sepsis. Staphylococcus aureus is a major cause of septic mortality. Neutrophils play an important role in the defense against bacterial infections. We have shown that a diet with high levels of dietary saturated fatty acids decreases survival in septic mice, but the mechanisms behind this remain elusive. The aim of the present study was to investigate how the differences in dietary fat composition affect survival and bacterial load after experimental septic infection and neutrophil function in uninfected mice. We found that, after S. aureus infection, mice fed a polyunsaturated high-fat diet (HFD-P) for 8 weeks had increased survival and decreased bacterial load during sepsis compared with mice fed a saturated high-fat diet (HFD-S), similar to mice fed a low-fat diet (LFD). Uninfected mice fed HFD-P had a higher frequency of neutrophils in bone marrow than mice fed HFD-S. In addition, mice fed HFD-P had a higher frequency of neutrophils recruited to the site of inflammation in response to peritoneal injection of thioglycolate than mice fed HFD-S. Differences between the proportion of dietary protein and carbohydrate did not affect septic survival at all. In conclusion, polyunsaturated dietary fat increased both survival and efficiency of bacterial clearance during septic S. aureus infection. Moreover, this diet increased the frequency and chemotaxis of neutrophils, key components of the immune response to S. aureus infections.

Oxidized dietary oils enhance immediate- and/or delayed-type allergic reactions in BALB/c mice.

BACKGROUND: The consumption of cooking oils may exacerbate some allergic diseases. In the present study, the effects of naturally oxidized olive oil on immediate- and/or delayed-type allergic reactions were investigated in BALB/c mice. METHODS: Mouse models of 3 types of allergic reactions: contact hypersensitivity (CHS), active cutaneous anaphylaxis (ACA), and DNFB-induced hypersensitivity, were orally administered naturally oxidized olive oil that was obtained by keeping the oil at room temperature for more than 3 years. The effects of ultraviolet ray (UV)-irradiated olive oil and other dietary oils as well as their possible oxidation products on CHS were also investigated. RESULTS: Naturally oxidized olive oil had a high peroxide value (POV) and exacerbated CHS, ACA, and DNFB-induced hypersensitivity in a POV-dependent manner. UV-irradiated olive oil, corn oil, sesame oil and triolein had high POVs, but almost the same acid value (AV) and thiobarbituric acid-reactive substance (TBARS) level as fresh oils. Fresh olive oil and the representative oxidation product with a high AV or TBARS level had no effect on CHS, whereas all UV-irradiated oils and naturally oxidized olive oil exacerbated it. CONCLUSIONS: Oxidized dietary oils that have high POVs exacerbated immediate- and/or delayed-type allergic reactions regardless of the different oil constituents or oxidation processes.

Dendritic cell activation, phagocytosis and CD69 expression on cognate T cells are suppressed by n-3 long-chain polyunsaturated fatty acids.

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are bioactive n-3 long-chain polyunsaturated fatty acids (LCPUFAs) in fish oil that exert immunosuppressive effects. A significant amount of literature shows that n-3 LCPUFAs suppress dendritic cell (DC) function in vitro; however, few studies have determined if the effects are emulated at the animal level. In this study, we first focused on the functional consequences of 5% (weight/weight) fish oil on splenic CD11c(+) DCs. Administration of n-3 LCPUFAs, modelling human pharmacological intake (2% of total kcal from EPA,1·3% from DHA), to C57BL/6 mice for 3 weeks reduced DC surface expression of CD80 by 14% and tumour necrosis factor-α secretion by 29% upon lipopolysaccharide stimulation relative to a control diet. The n-3 LCPUFAs also significantly decreased CD11c(+) surface expression and phagocytosis by 12% compared with the control diet. Antigen presentation studies revealed a 22% decrease in CD69 surface expression on transgenic CD4(+) T lymphocytes activated by DCs from mice fed fish oil. We then determined if the functional changes were mechanistically associated with changes in lipid microdomain clustering or plasma membrane microviscosity with n-3 LCPUFAs, as reported for B and T lymphocytes. Fish oil administration to mice did not influence cholera-toxin induced lipid microdomain clustering or microviscosity, even though EPA and DHA levels were significantly elevated relative to the control diet. Overall, our data show that n-3 LCPUFAs exert immunosuppressive effects on DCs, validating in vitro studies. The results also show that DC microdomain clustering and microviscosity were not changed by the n-3 LCPUFA intervention used in this study.

Immunomodulatory action of dietary fish oil and targeted deletion of intestinal epithelial cell PPARδ in inflammation-induced colon carcinogenesis.

The ligand-activated transcription factor peroxisome proliferator-activated receptor (PPAR)-δ is highly expressed in colonic epithelial cells; however, the role of PPARδ ligands, such as fatty acids, in mucosal inflammation and malignant transformation has not been clarified. Recent evidence suggests that the anti-inflammatory/chemoprotective properties of fish oil (FO)-derived n-3 polyunsaturated fatty acids (PUFAs) may be partly mediated by PPARδ. Therefore, we assessed the role of PPARδ in modulating the effects of dietary n-3 PUFAs by targeted deletion of intestinal epithelial cell PPARδ (PPARδ(ΔIEpC)). Subsequently, we documented changes in colon tumorigenesis and the inflammatory microenvironment, i.e., local [mesenteric lymph node (MLN)] and systemic (spleen) T cell activation. Animals were fed chemopromotive [corn oil (CO)] or chemoprotective (FO) diets during the induction of chronic inflammation/carcinogenesis. Tumor incidence was similar in control and PPARδ(ΔIEpC) mice. FO reduced mucosal injury, tumor incidence, colonic STAT3 activation, and inflammatory cytokine gene expression, independent of PPARδ genotype. CD8(+) T cell recruitment into MLNs was suppressed in PPARδ(ΔIEpC) mice. Similarly, FO reduced CD8(+) T cell numbers in the MLN. Dietary FO independently modulated MLN CD4(+) T cell activation status by decreasing CD44 expression. CD11a expression by MLN CD4(+) T cells was downregulated in PPARδ(ΔIEpC) mice. Lastly, splenic CD62L expression was downregulated in PPARδ(ΔIEpC) CD4(+) and CD8(+) T cells. These data demonstrate that expression of intestinal epithelial cell PPARδ does not influence azoxymethane/dextran sodium sulfate-induced colon tumor incidence. Moreover, we provide new evidence that dietary n-3 PUFAs attenuate intestinal inflammation in an intestinal epithelial cell PPARδ-independent manner.

Effects of dietary n-3 highly unsaturated fatty acids on growth, nonspecific immunity, expression of some immune related genes and disease resistance of large yellow croaker (Larmichthys crocea) following natural infestation of parasites (Cryptocaryon irritans).

The study was conducted to investigate the effects of dietary n-3 highly unsaturated fatty acid (n-3 HUFA) on growth, nonspecific immunity, expression of some immune related genes and disease resistance of juvenile large yellow croaker (Larmichthys crocea) following natural infestation of parasites (Cryptocaryon irritans). Six isoproteic and isolipidic diets were formulated with graded levels of n-3 HUFA ranging from 0.15% to 2.25% of the dry weight and the DHA/EPA was approximately fixed at 2.0. Each diet was randomly allocated to triplicate groups of fish in floating sea cages (1.0 × 1.0 × 1.5 m), and each cage was stocked with 60 fish (initial average weight 9.79 ± 0.6 g). Fish were fed twice daily (05:00 and 17:00) to apparent satiation for 58 days. Results showed that moderate n-3 HUFA level (0.98%) significantly enhanced growth compared with the control group (0.15% HUFA) (P < 0.05), while higher n-3 HUFA levels (1.37%, 1.79% and 2.25%) had detrimental effects on the growth though no significance was found (P > 0.05). Nitro blue tetrazolium (NBT) positive leucocytes percentage of head kidney and serum superoxide dismutase (SOD) activity increased with increasing n-3 HUFA from 0.15% to 0.60%, and decreased with further increase of n-3 HUFA from 0.60% to 2.25% (P < 0.05). Serum lysozyme activity increased significantly as n-3 HUFA increased from 0.15% to 1.37%, and then decreased with n-3 HUFA from 1.37% to 2.25% (P > 0.05). There were no significant differences in phagocytosis index (PI) of head kidney leucocytes among dietary treatments (P > 0.05). The hepatic mRNA expression of Toll-like receptor 22 (TLR22) and Myeloid differentiation factor 88 (MyD88) was significantly up-regulated in fish fed the diets with low or moderate levels, while in kidney this increment was only found at specific sampling time during the natural infestation of parasites. The 13 d cumulative mortality rate following natural infestation of parasites decreased with n-3 HUFA increased from 0.15% to 0.60% (P < 0.05), and significantly increased with n-3 HUFA from 0.60% to 2.25% (P < 0.05). Results of this study suggested that fish fed low or moderate dietary n-3 HUFA had higher growth, nonspecific immune responses, expression levels of some immune related genes and disease resistance of large yellow croaker following natural infestation of parasites and dietary n-3 HUFA may regulate fish immunity and disease resistance by altering the mRNA expression levels of TLR22 and MyD88.

Replacement of dietary fish oil by vegetable oils affects humoral immunity and expression of pro-inflammatory cytokines genes in gilthead sea bream Sparus aurata.

Commercial gilthead sea bream feeds are highly energetic, fish oil traditionally being the main lipid source. But the decreased fish oil production together with the increased prices of this oil encourages its substitution by vegetable oils, imposing new nutritional habits to aquaculture species. Partial replacement of fish oil by vegetable oils in diets for marine species allows good feed utilization and growth but may affect fish health, since imbalances in dietary fatty acids may alter fish immunological status. The effect of dietary oils on different aspects of fish immune system has been reported for some species, but very little is known about the effect of dietary oils on immune-related genes expression in fish. Thus, the objective of this study was to elucidate the role of dietary oils on the expression of two pro-inflammatory cytokines, Tumor Necrosis Factor-α (TNF-α) and Interleukine 1ß (IL-1ß) on intestine and head kidney after exposure to the bacterial pathogen Photobacterium damselae sp. piscicida. For that purpose, 5 iso-nitrogenous and iso-lipidic diets (45% crude protein, 22% crude lipid content) were formulated. Anchovy oil was the only lipid source used in the control diet (FO), but in the other diets, fish oil was totally (100%) or partially (70%) substituted by linseed (rich in n-3 fatty acids) or soybean (rich in n-6 fatty acids) (100L, 100S, 70L, 70S). Fish were fed experimental diets during 80 days and after this period were exposed to an experimental intestinal infection with the pathogen. Serum and tissue samples were obtained at pre-infection and after 1, 3 and 7 days of infection. RNA was extracted and cDNA was synthesized by reverse transcription from intestine and head kidney and the level expression of TNF-α and IL-1ß were assayed by using quantitative real time PCR. The expression level of genes analysed was represented as relative value, using the comparative Ct method (2(-ΔΔCt)). Serum anti-bacterial activity was measured as serum bactericidal capacity and lysozyme activity. Reduction of FO tends to reduce basal (pre-infection) genetic expression of both cytokines. However, complete FO replacement caused an over expression of both pro-inflammatory cytokines, particularly after 3 days of induced infection in fish fed soybean oil based diets. On the other hand, fish fed diets with low content of n-6 fatty acids showed better serum bactericidal capacity after infection, suggesting that the substitution of fish oil by vegetable oils containing high levels of n-6 fatty acids may induce imbalances on fish immune response, leading to a lower potential response against infections.

Pomegranate seed oil consumption during a period of high-fat feeding reduces weight gain and reduces type 2 diabetes risk in CD-1 mice.

The health benefits of pomegranate consumption have recently received considerable scientific focus, with most studies examining fruit and/or juice consumption. Pomegranate seed oil (POMo) is a rich source of 9-cis, 11-trans conjugate linolenic acid (CLA), which may offset the side-effects associated with weight gain. Male, wild-type CD-1 mice were divided into one of three groups (twenty per group): high-fat (HF), HF+seed oil (HF + POMo) or lean control (LN). In HF and HF + POMo, mice were provided access ad libitum to a high-fat chow (60 % of energy from fat). HF + POMo was supplemented with 61.79 mg POMo/d. LN consumed a restricted low-fat (10 % of energy from fat) chow to maintain body weight within 5 % of initial weight. Plasma was analysed for biomarkers associated with cholesterol profile (total cholesterol, HDL and TAG), glucose sensitivity (glucose and insulin), adipose tissue accumulation (leptin and adiponectin) and systemic low-grade inflammation (C-reactive protein and haptoglobin). The key findings of this study were that weight gain was associated with an increase in biomarkers of cholesterol profile, glucose sensitivity, adipose tissue accumulation and systemic low-grade inflammation (P < 0.05). POMo only altered body weight accumulation, final body weight, leptin, adiponectin and insulin (P < 0.05). We found that despite a similar level of energy intake, HF mice had a greater concentration of leptin and a lower concentration of adiponectin compared to HF + POMo mice. POMo intake was associated with an improvement in insulin sensitivity, suggesting that risk of developing type 2 diabetes may have been reduced; however, CVD risk did not change.

The Influence of Dietary Fatty Acids on Immune Responses.

Diet-derived fatty acids (FAs) are essential sources of energy and fundamental structural components of cells. They also play important roles in the modulation of immune responses in health and disease. Saturated and unsaturated FAs influence the effector and regulatory functions of innate and adaptive immune cells by changing membrane composition and fluidity and by acting through specific receptors. Impaired balance of saturated/unsaturated FAs, as well as n-6/n-3 polyunsaturated FAs has significant consequences on immune system homeostasis, contributing to the development of many allergic, autoimmune, and metabolic diseases. In this paper, we discuss up-to-date knowledge and the clinical relevance of the influence of dietary FAs on the biology, homeostasis, and functions of epithelial cells, macrophages, dendritic cells, neutrophils, innate lymphoid cells, T cells and B cells. Additionally, we review the effects of dietary FAs on the pathogenesis of many diseases, including asthma, allergic rhinitis, food allergy, atopic dermatitis, rheumatoid arthritis, multiple sclerosis as well as type 1 and 2 diabetes.

Fatty acid intake and asthma symptoms in Japanese children: the Ryukyus Child Health Study.

BACKGROUND: It has been hypothesized that increased consumption of n-6 polyunsaturated fatty acids and decreased consumption of n-3 polyunsaturated fatty acids have contributed to the recent increased prevalence of asthma. OBJECTIVES: The present cross-sectional study examined the association of intake of specific types of fatty acids with the prevalence of asthma symptoms using data from the Ryukyus Child Health Study. METHODS: Study subjects were 25,033 schoolchildren aged 6-15 years in Okinawa, Japan. Symptoms of wheeze and asthma were defined according to diagnostic criteria from the International Study of Asthma and Allergies in Childhood. Information on dietary factors was collected using a self-administered brief diet history questionnaire for children. Adjustment was made for age, sex, number of siblings, smoking in the household, body mass index, paternal and maternal history of allergic diseases, and paternal and maternal educational level. RESULTS: Intake of polyunsaturated fatty acids, n-3 and n-6 polyunsaturated fatty acids and linoleic acid (18:2 n-6) was independently associated with an increased prevalence of wheeze--the multivariate odds ratios for the highest quintile were 1.19 (95% confidence interval [CI], 1.05-1.35), 1.17 (95% CI, 1.03-1.34), 1.19 (95% CI, 1.04-1.35), and 1.20 (95% CI, 1.06-1.37), respectively. There was no measurable relationship of consumption of alpha-linolenic (18:3 n-3), eicosapentaenoic (20:5 n-3), docosahexaenoic (22:6 n-3) or arachidonic acid (20:4 n-6) or the ratio of n-3 to n-6 polyunsaturated fatty acids with the prevalence of wheeze. Consumption of total fat, saturated fatty acids, monounsaturated fatty acids and cholesterol were not evidently related to wheeze. No material dose-response association was found between the intake of any of the types of fatty acids considered and the prevalence of asthma. CONCLUSIONS: The findings suggest that consumption of both n-3 and n-6 polyunsaturated fatty acids, especially linoleic acid, may be associated with an increased prevalence of wheeze.

Long-chain polyunsaturated fat supplementation in children with low docosahexaenoic acid intakes alters immune phenotypes compared with placebo.

OBJECTIVES: The objectives of this study were to assess the effects of long-term supplementation with arachidonic acid (AA; 20:4n-6) and docosahexaenoic acid (DHA; 22:6n-3) on cell phenotypes and cytokine production in children. PATIENTS AND METHODS: This randomized, double-blind, placebo-controlled trial provided children, (ages 5-7 years; n = 37) who had low intakes of DHA, with a dietary supplement containing AA (20-30 mg daily) and DHA (14-21 mg daily) or a placebo supplement for 7 months. After the supplementation period, a series of stimulants (pokeweed mitogen, phytohemagluttinin, lipopolysaccharide, beta-lactoglobulin, and ibuprofen) was used to stimulate peripheral blood mononuclear cells ex vivo. Antigen expression on T cells (CD25 and CD80), B cells, and macrophages (CD54), as well as cytokine production (interleukin [IL]-4, IL-10, tumor necrosis factor, IL-2, IL-6, and interferon-gamma), were measured using flow cytometry, monoclonal antibodies, and cytometric bead array, respectively. RESULTS: Mononuclear cells from children provided long-chain polyunsaturated fatty acids (LCPUFAs) had fewer CD8+ cells expressing CD25 and CD80 compared with placebo after exposure to each mitogen. The LCPUFA group also exhibited lower proportions of CD14+ cells after stimulation with beta-lactoglobulin and ibuprofen. The proportion of CD54+ cells was 2-fold higher for the LCPUFA group compared with placebo after exposure to ibuprofen and beta-lactoglobulin (P < 0.05). Each of these immune effects related to the amount of AA and/or DHA in the plasma and erythrocyte phospholipids. CONCLUSIONS: Alterations in cell phenotypes were evident when children were supplemented with AA and DHA. The results of this study have important implications for immune development and sensitivity to antigens in children.

Dietary eicosapentaenoic acid and docosahexaenoic acid equally incorporate as decosahexaenoic acid but differ in inflammatory effects.

OBJECTIVE: The omega-3 polyunsaturated fatty acids are involved in the modulation of the immune response. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) produced from dietary precursors may not be sufficient to match nutritional requirements and thus should be included in our diet. In this sense, the administration of higher amounts of DHA than of EPA in infant formulations is recommended. The aims of this work were to demonstrate that dietary administration of EPA or DHA to mice allows reaching similar tissue DHA levels and to compare their anti-inflammatory effects and mechanisms of action. METHODS: Balb/c mice were fed diets enriched with EPA or DHA for 3 wk. Twelve hours before sacrifice, a contact dermatitis was induced in the ears of the animals. Tissue fatty acid contents were determined. Cytokine and immunoglobulin concentrations were measured by enzyme-linked immunosorbent assay, and ears were collected to analyze local inflammatory effects. RESULTS: The DHA concentrations attained in tissues were similar to the two diets, whereas the EPA concentration increased only when the diet was enriched with this polyunsaturated fatty acid. Although EPA and DHA reduced ear inflammation, EPA reduced neutrophil infiltration in the ears more efficiently. EPA was associated with a greater reduction in the systemic macrophage inflammatory response and T-helper type 2 response and with increased interleukin-10 production. CONCLUSION: Similar levels of DHA in tissues are reached in mice fed an EPA- or a DHA-enriched diet. Dietary EPA and DHA show anti-inflammatory properties, but EPA appears to be more potent.

Immune modulation by parenteral lipid emulsions.

Total parenteral nutrition is the final option for nutritional support of patients with severe intestinal failure. Lipid emulsions constitute the main source of fuel calories and fatty acids (FAs) in parenteral nutrition formulations. However, adverse effects on patient outcomes have been attributed to the use of lipids, mostly in relation to impaired immune defenses and altered inflammatory responses. Over the years, this issue has remained in the limelight, also because technical advances have provided no safeguard against the most daunting problems, ie, infectious complications. Nevertheless, numerous investigations have failed to produce a clear picture of the immunologic characteristics of the most commonly used soybean oil-derived lipid emulsions, although their high content of n-6 polyunsaturated FAs (PUFAs) has been considered a drawback because of their proinflammatory potential. This concern initiated the development of emulsions in which part of the n-6 FA component is replaced by less bioactive FAs, such as coconut oil (rich in medium-chain saturated FAs) or olive oil (rich in the n-9 monounsaturated FA oleic acid). Another approach has been to use fish oil (rich in n-3 PUFA), the FAs of which have biological activities different from those of n-6 PUFAs. Recent studies on the modulation of host defenses and inflammation by fish-oil emulsions have yielded consistent data, which indicate that these emulsions may provide a tool to beneficially alter the course of immune-mediated conditions. Although most of these lipids have not yet become available on the US market, this review synthesizes available information on immunologic characteristics of the different lipids that currently can be applied via parenteral nutrition support.

Prenatal fatty acid status and immune development: the pathways and the evidence.

This review explores the effects of dietary long chain polyunsaturated fatty acids (LCPUFA) on various aspects of early immune development and their potential role in the development or the prevention of immune disease. Modern diets have become increasingly rich in n-6 LCPUFA and relatively n-3 LCPUFA deficient. These potentially "pro-inflammatory" dietary changes have clear implications for the immature and developing fetal immune system. It is now well known that immunological abnormalities precede the development of allergic disease and are frequently evident at birth or in the first months of life. This has lead to the hypothesis that potential effects of LCPUFA could be greatest in very early life before immune responses and clinical phenotype are established. Here we summarise the evidence that patterns of LCPUFA exposure in pregnancy can influence aspects of fetal immune in ways that are consistent with the immunological properties of these nutrients in adults. Specifically, human studies have shown that higher levels of n-3 LCPUFA are associated with reduction in neonatal oxidative stress, reduced production of inflammatory leukotienne B4 (LTB4) and altered T cell function. Inverse correlations between n-3 LCPUFA levels and neonatal T cell cytokine production, are consistent with adult studies showing reduction in T cell cytokine production with fish oil supplementation. At this stage the relevance of these effects in the prevention of disease is unclear. Although there have been no effects of postnatal fish oil supplementation (from 6 months of age) on allergy prevention, preliminary studies suggest possible merits in pregnancy and there are ongoing pregnancy intervention studies to address this more definitively.

[Peculiarities of the cellular blood composition of the rats, receiving mare's milk fat during immunization].

The influence of polyunsaturated fatty acids of mare 's milk fat on the cellular composition of the peripheral blood was investigated in male rats after a prolonged period of feeding. Animals were fed with isocaloric purified diet, part fats which on 30% (on caloricity) of fat marers milk (in experements group), in control groups - combination of lard and sunflower oil in which the ratio of fatty acids omega-6/omega-3 was equal to 0,76. At the end of the 6-th week of feeding (on the 6-th day after a single immunization with a 5% sheep erythrocyte suspension) the immunized animals have demonstrated leucocytosis that was marked by a considerable rise in the level of neutrophils and lymphocytes and a twofold increase of monocyte number. Such characteristic changes in leucocytogram exept low monocytosis were not revealed in immunized rats at the end of the 8-th week of feeding (on the 13-th day after a repeated immunization).

High-Fat Diets Containing Different Amounts of n3 and n6 Polyunsaturated Fatty Acids Modulate Inflammatory Cytokine Production in Mice.

Dysregulation of adipokines is a hallmark of obesity. Polyunsaturated fatty acids in fish oil may exert anti-inflammatory effects on adipose tissue mitigating the dysregulation of adipokines thereby preventing obesity. This study investigated the effects of high-fat diets containing different amounts of n3 polyunsaturated fatty acids (PUFA) on adiposity and adipokine production in mice. Mice were fed a low-fat or a high-fat diet with 16 or 45 % of energy from corn oil (low n3 PUFA) in comparison with a high-fat diet containing soybean or high-oleic sunflower oil (adequate n3 PUFA) or flaxseed or fish oil (high n3 PUFA) for 11 weeks. High-fat diets, regardless of types of oils, significantly increased body fat mass and body weights compared to the low-fat diet. Adipose fatty acid composition and contents reflected dietary fatty acid profiles. The high-fat fish oil diet significantly increased adiponectin and reduced leptin concentrations in both plasma and adipose tissue; it did not elevate plasma insulin concentration compared to the high-fat corn oil diet. All high-fat diets elevated concentrations of plasminogen activator inhibitor-1 (PAI-1) and monocyte chemoattractant protein-1 (MCP-1) but lowered resistin concentrations in both plasma and adipose tissue. In conclusion, fish oil may be beneficial in improving insulin sensitivity by upregulation of adiponectin and downregulation of leptin production; n3 and n6 PUFA do not play a role at the dietary levels tested in reducing adiposity and production of pro-inflammatory cytokines (leptin, PAI-1, MCP-1 and resistin) and anti-inflammatory cytokine adiponectin.

Dietary n-3 polyunsaturated fatty acids increase T-lymphocyte phospholipid mass and acyl-CoA binding protein expression.

Dietary flaxseed oil, which is enriched in alpha-linolenic acid, and fish oil, which is enriched in EPA and DHA, possess anti-inflammatory properties when compared with safflower oil, which is enriched in linoleic acid. The influence of flaxseed oil and fish oil feeding on lipid metabolism in T-lymphocytes is currently unknown. This study directly compared the effects of feeding safflower oil, flaxseed oil, and fish oil for 8 wk on splenic T-lymphocyte proliferation, phospholipid mass, and acyl-CoA binding protein expression in the rat. The data show that both flaxseed oil and fish oil increased acyl-CoA binding protein expression and phosphatidic acid mass in unstimulated T-lymphocytes when compared with safflower oil feeding. Fish oil feeding increased cardiolipin mass, whereas flaxseed oil had no effect. After stimulation, flaxseed oil and fish oil blunted T-lymphocyte interleukin-2 production and subsequent proliferation, which was associated with the lack of increased acyl-CoA binding protein expression. The results reported show evidence for a novel mechanism by which dietary flaxseed oil and fish oil suppress T-lymphocyte proliferation via changes in acyl-CoA binding protein expression and phospholipid mass.

n-3 polyunsaturated fatty acids inhibit the antigen-presenting function of human monocytes.

Diets rich in n-3 polyunsaturated fatty acids (PUFAs) are associated with suppression of cell-mediated immune responses, but the mechanisms are unclear. We hypothesized that n-3 PUFAs can inhibit the function of human antigen-presenting cells. A prerequisite for this role of blood monocytes is the cell surface expression of major histocompatibility complex (MHC) class II molecules [human leukocyte antigen (HLA)-DR, -DP, and -DQ], aided by the presence of intercellular adhesion molecule-1 (ICAM-1) and leukocyte function associated antigens 1 and 3. We showed previously that the n-3 PUFA eicosapentaenoic acid (EPA) inhibits the expression of HLA-DR on unstimulated human monocytes in vitro, but that docosahexaenoic acid (DHA) enhances its expression. However, both n-3 PUFAs suppress the expression of HLA-DR, HLA-DP, and ICAM-1 on interferon-gamma-activated monocytes. We also established that dietary fish-oil supplementation can inhibit the expression of these surface molecules on circulating human monocytes. We subsequently showed that when EPA and DHA were combined in the same ratio as is commonly found in fish-oil-supplement capsules (3:2), there was no significant effect in vitro on the expression of HLA-DR on unstimulated monocytes, but the expression on activated monocytes remained significantly inhibited. In the same in vitro system, the ability of activated monocytes to present antigen to autologous lymphocytes was significantly reduced after culture with the combined n-3 PUFAs. These findings provide one potential mechanism for the beneficial effect of fish oil in the treatment of rheumatoid arthritis, a disorder associated with elevated expression of MHC class II and adhesion molecules on monocytes present within affected joints.

Effects of dietary fish oil on survival rate, plasma amino acid pattern, and inflammatory-related mediators in diabetic rats with sepsis.

This study was designed to investigate the effects of dietary fish oil on survival rates, plasma amino acid profiles, and inflammatory-related mediators in diabetic rats with sepsis. Diabetes mellitus (DM) was induced in rats by streptozotocin. The DM rats were maintained for 4 weeks on medium fat (10%, w/w) diets containing either fish oil or safflower oil. After that, sepsis was induced by cecal ligation and puncture (CLP). There were 2 groups in this study: fish oil sepsis group (FOS) and safflower oil sepsis group (SOS). The survival rate was observed after CLP. Also, changes of the amino acid pattern as well as interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, prostaglandin (PG) E(2)at 6, 12, and 24 h after CLP were investigated. The results demonstrated that survival rates were not significantly different between the 2 groups. Plasma arginine levels were significantly lower in sepsis groups than that in the DM-chow group, regardless of whether the diabetic rats were fed fish oil or safflower oil. No significant differences were observed in plasma valine, leucine, isoleucine, glutamine, or arginine concentrations between the FOS and SOS groups at different time points. Concentrations of IL-1 beta in peritoneal lavage fluid (PLF) at 6 h and TNF-alpha at 6 h as well as at 12 h after CLP in the FOS group were significantly higher than those in the SOS group. PGE(2)levels in PLF, by contrast, were lower in the FOS group at 6 and 12 h after CLP than in the SOS group. These results suggest that differences in IL-1 beta, TNF-alpha, and PGE(2)levels in PLF in the early period of sepsis did not influence the survival rates and plasma amino acid profiles of the FOS and SOS groups. Compared with safflower oil, feeding diabetic rats with fish oil had no beneficial effects on survival rates and muscle protein breakdown. The immunologic impact of dietary n-3 polyunsaturated fatty acids on diabetic rats with sepsis requires further investigation.

Lipid modulation and systemic inflammation.

N-6 and n-3 PUFAs from the diet are absorbed and reach the cell where they interact with fatty acid binding proteins within cell membranes and cytoplasm. They are processed in the endoplasmic reticulum (desaturation-elongation reactions, lipid synthesis, eicosanoid and epoxide production) and in peroxisomes (beta-oxidation, synthesis, oxidation products). They interact with receptors, ion channels, and nuclear elements; the result is modulation of gene expression. PUFA-induced alterations result in modulation of local and systemic inflammation and inflammatory disease activity.