Dietary polyunsaturated fatty acids (C18:2 omega6 and C18:3 omega3) do not suppress hepatic lipogenesis

Omega 3 polyunsaturated fatty acids are promoted as beneficial in the prevention of metabolic and cardiovascular diseases. In general, dietary omega 3 fatty acids are derived from plant sources as linolenic acid (LNA, C18:3 omega3) the precursor to eicosapentaenoic acid (EPA, C20:5 omega3) and docosahexaenoic acid (DHA, C22:6 omega3). However, it remains unclear if the polyunsaturated fatty acid (PUFA) LNA can provide the same health benefits as the very long chain highly unsaturated fatty acids (HUFA) EPA and DHA generally derived from oily fish. In this study, mice were fed synthetic diets containing lard (low in PUFA and HUFA), canola oil (to supply PUFA), or a mixture of menhaden and arasco (fish and fungal) oils (to supply HUFA) for 8 weeks. The diets were neither high in calories nor fat, which was supplied at 6%. The lard and canola oil diets resulted in high levels of hepatic triglycerides and cholesterol and elevation of lipogenic gene expression. By comparison livers from mice fed the fish/fungal oil diet had low levels of lipid accumulation and more closely resembled livers from mice fed standard laboratory chow. SREBP1c and PPARgamma gene and protein expression were high in livers of animals fed diets containing lard or canola oil compared with fish/fungal oil. Hepatic fatty acid analyses indicated that dietary PUFA were efficiently converted to HUFA regardless of source. Therefore, differences in hepatic lipid levels and gene expression between dietary groups were due to exogenous fatty acid supplied rather than endogenous pools. These results have important implications for understanding the regulation of hepatic lipogenesis by dietary fatty acids.     

Replacement of dietary fish oil for Atlantic salmon parr (Salmo salar L.) with a stearidonic acid containing oil has no effect on omega-3 long-chain polyunsaturated fatty acid concentrations

The worldwide increase in aquaculture production and the concurrent decrease of wild fish stocks has made the replacement of fish oil in aquafeeds an industry priority. Oil from a plant source Echium plantagineum L., Boraginaceae, has high levels of stearidonic acid (SDA, 18:4omega3, 14%) a biosynthetic precursor of omega-3 long-chain (> or =C(20)) polyunsaturated fatty acids (omega3 LC-PUFA). Atlantic salmon (Salmo salar L.) parr were fed a control fish oil diet (FO) or one of 3 experimental diets with 100% canola oil (CO) 100% SDA oil (SO), and a 1:1 mix of CO and SDA oil (MX) for 42 days. There were no differences in the growth or feed efficiency between the four diets. However, there were significant differences in the fatty acid (FA) profiles of the red and white muscle tissues. Significantly higher amounts of SDA, eicosapentaenoic acid (20:5omega3, EPA), docosahexaenoic acid (22:6omega3, DHA) and total omega3 FA occurred in both red and white muscle tissues of fish fed SO and FO compared with those fed CO. Feeding SO diet resulted in omega3 LC-PUFA amounts in the white and red muscle being comparable to the FO diet. This study shows that absolute concentration (mug/g) of EPA, DHA and total omega3 have been maintained over 6 weeks for Atlantic salmon fed 14% SDA oil. The balance between increased biosynthesis and retention of omega3 LC-PUFA to maintain the concentrations observed in the SO fed fish remains to be conclusively determined, and further studies are needed to ascertain this.     

Modulation of phorbol ester-elicited events in mouse epidermis by dietary n-3 and n-6 fatty acids

Because arachidonic acid-derived eicosanoids are potent modulators of hyperproliferation and inflammation during skin tumor promotion with the phorbol ester, 12-0-tetradecanoylphorbol-13-acetate (TPA) (17, 18), it was hypothesized that dietary modification of epidermal fatty acids might modulate TPA-induced biochemical events in mouse skin. Semipurified diets containing 10% total fat composed of corn oil (CO) or a combination of CO and menhaden oil (MO) or coconut oil (CT) were fed to SENCAR mice for 4 weeks. Fatty acid composition of epidermal phospholipids generally reflected fatty acid composition of dietary oils fed to the mice. Since fatty acid-derived eicosanoids are thought to be essential in tumorigenesis, we compared the effects of dietary fats on prostaglandin E (PGE) production in epidermis treated with a single dose of TPA. TPA-induced PGE production in mouse epidermis from mice fed the MO diet was significantly reduced compared to PGE production in epidermal homogenates from mice fed the CO or CT diets. Type of dietary fats did not appear to modulate TPA-induced vascular permeability, however hyperplasia was slightly elevated in skins of mice fed MO. The subcellular distribution of protein kinase C, the plasma membrane receptor for TPA predominantly located in the cytosol (80%), was altered in epidermis from mice fed the MO diet compared to preparations from mice fed CO or CT diets which exhibited normal protein kinase C distribution. Our results suggest that n-3 rich dietary lipids modulate TPA-elicited events in mouse skin to a greater extent than diets containing higher proportions of saturated or n-6 fatty acids.     

Dietary fats affect macrophage-mediated cytotoxicity towards tumour cells

In the present study, the effects of feeding mice diets of different fatty acid compositions on the production of TNF-alpha and nitric oxide by lipopolysaccharide-stimulated peritoneal macrophages and on macrophage-mediated cytotoxicity towards L929 and P815 cells were investigated. C57Bl6 mice were fed on a low-fat (LF) diet or on high-fat diets (21% fat by weight), which included coconut oil (CO), olive oil (OO), safflower oil (SO) or fish oil (FO) as the principal fat source. The fatty acid composition of the macrophages was markedly influenced by that of the diet fed. Lipopolysaccharide (LPS)-stimulated macrophages from FO-fed mice showed significantly lower production (up to 80%) of PGE2 than those from mice fed on each of the other diets. There was a significant positive linear correlation between the proportion of arachidonic acid in macrophage lipids and the ability of macrophages, to produce PGE2. Lipopolysaccharide-stimulated TNF-alpha production by macrophages decreased with increasing unsaturated fatty acid content of the diet (i.e. FO < SO < OO < CO < LF). Macrophages from FO-fed mice showed significantly lower production of TNF-alpha than those from mice fed on each of the other diets. Nitrite production was highest for LPS-stimulated macrophages from mice fed on the LF diet. Macrophages from FO-fed mice showed significantly higher production of nitrite than those from mice fed on the OO and SO diets. Compared with feeding the LF diet, feeding the CO, OO or SO diets significantly decreased macrophage- mediated killing of P815 cells (killed by nitric oxide). Fish oil feeding did not alter killing of P815 cells by macrophages, compared with feeding the LF diet; killing of P815 cells was greater after FO feeding than after feeding the other high fat diets. Compared with feeding the LF diet, feeding the OO or SO diets significantly decreased macrophage-mediated killing of L929 cells (killed by TNF). Coconut oil or FO feeding did not alter killing of L929 cells by macrophages, compared with feeding the LF diet. It is concluded that the type of fat in the diet affects macrophage composition and alters the ability of macrophages to produce cytotoxic and immunoregulatory mediators and to kill target tumour cells.     

Reduction in serum IL-6 after vacination of breast cancer patients with tumour-associated antigens is related to estrogen receptor status

Elevated serum IL-6 concentrations have been associated with poor prognosis in a variety of cancers, and decreases in serum IL-6 concentrations have been reported after chemotherapy. We have demonstrated that serum IL-6 concentrations are elevated in breast cancer patients [normal women 0.7 +/- 2.5 pg/ml (n=36), breast cancer patients 38.3 +/- 138.7 pg/ml (n = 111)]. After vaccination of breast cancer patients with a combination of tumour-associated antigens and biological adjuvants (IL-2 and GM-CSF), the concentration of IL-6 decreased significantly (P<0.05) to 8.1 +/- 14.6 pg/ml (n=85). Other studies have shown that oestrogen suppresses IL-6 production in oestrogen receptor positive breast cancer cells. We have demonstrated that the decrease in IL-6 associated with vaccination is related to the oestrogen receptor status of the tumours from breast cancer patients, as a decrease in IL-6 from 124.0 +/- 267.5 pg/ml (n=26) to 6.2 +/- 11.0 pg/ml (n=34) only occurs in patients with oestrogen receptor negative tumours. The IL-6 concentration in breast cancer patients with oestrogen receptor positive tumours remained unchanged (9.5 pg/ml before vaccination, and 9.3 pg/ml after vaccination). These results suggest that postmenopausal women with oestrogen receptor negative breast cancers, who do not respond well to either hormonal therapy with tamoxifen or adjuvant chemotherapy, may have a significant response to vaccination with autologous tumour-associated antigens.     

Effects of dietary omega3 and omega6 lipids and vitamin E on proliferative response, lymphoid cell subsets, production of cytokines by spleen cells, and splenic protein levels for cytokines and oncogenes in MRL/MpJ-lpr/lpr mice

omega3 Fatty acid rich fish oil (FO) and vitamin E may delay the progress of certain autoimmune diseases. The present study examined the mechanisms of action of omega3 lipids and vitamin E in autoimmune-prone MRL/lpr mice suffering from extensive lymphoproliferation, lupus-like symptoms, and accelerated aging. To determine whether the effects of omega3 lipids in autoimmune disease is linked to vitamin E levels, weanling female MRL/lpr and congenic control MRL/++ mice were fed diets containing 10% corn oil (CO) or 10% FO at two levels of vitamin E (75 IU or 500 IU/kg diet) for 4 months. The appearance of lymph nodes was delayed in the mice fed FO, and higher levels of FO offered further protection against the appearance of lymph nodes. Analysis of the spleen cells revealed that the cells positive for Thy.1 and Fas were significantly higher in the MRL/++ mice. The groups fed high levels of vitamin E generally exhibited higher levels of Fas. The proliferative response of splenocytes of MRL/++ mice to mitogens was significantly higher compared with MRL/lpr mice. Interleukin (IL)-10 production by spleen cells was significantly higher in FO-fed MRL/lpr mice than in CO-fed mice. In mice fed a high level of vitamin E, the production of IL-12 and tumor necrosis factor-alpha was significantly lower and IL-2 was significantly higher than in animals fed a low level of vitamin E. Proinflammatory cytokines were higher in the MRL/lpr mice and both FO and vitamin E lowered the levels of proinflammatory cytokines and lipid mediators. Western blots revealed that c-myc and c-ras were significantly lower and IL-2 and transforming growth factor (TGF)-beta1 levels were significantly higher in the spleens of MRL/++ mice. FO lowered c-myc and high levels of vitamin E in the diets normalized the levels of TGF-beta1 in MRL/lpr mice. The observations from this study suggest that both FO and vitamin E modulate the levels of specific cytokines, decrease the levels of proinflammatory cytokines, inflammatory lipid mediators, and c-myc, and increase TGF-beta1 levels in spleens of MRL/lpr mice and thus may delay the progress of autoimmune diseases.     

Effects of dietary omega3 and omega6 lipids and vitamin E on chemokine levels in autoimmune-prone MRL/MpJ-lpr/lpr mice

Elevated levels of chemokines, such as Regulated upon Activation, Normal T cell Expressed and Secreted (RANTES), Monocyte Chemotactic Protein-1 (MCP-1), Macrophage Inflammatory Protein-1alpha (MIP-1alpha), and Macrophage Inflammatory Protein-1beta (MIP-1beta) have been found in rheumatoid arthritis (RA) and juvenile arthritis (JA), and they may be associated with the pathogenesis of these diseases. These chemokines are implicated in the migration of specific leukocytes into the joints. Omega-3 (omega3) fatty acid rich-fish oil (FO) and vitamin E may delay the progress of certain autoimmune diseases. The present study was designed to understand the effects of dietary lipids (omega-6 and omega-3 fatty acids) and vitamin E on the production of chemokines in autoimmune-prone MRL/lpr (a mouse model for RA) and congenic control MRL/++ mice. The MRL mice were fed for 4.5 months omega-6 and omega-3 diets that varied in lipid sources (corn oil; CO and fish oil; FO) and vitamin E levels (269 I.U./kg and 694 I.U./kg diet). Spleen cells were isolated and cultured aseptically in the presence of PHA for 48 h at 37 degrees C and the levels of chemokines (RANTES, JE/MCP-1 and MIP-1alpha) were determined in the cell-free supernatants. The levels of RANTES and JE/MCP-1 were significantly higher in MRL/lpr mice compared to MRL/++ mice. The FO had differential effect on RANTES and MCP-1 production by spleen cells. The production of RANTES and JE/MCP-1 by spleen cells in mice fed the FO diets was significantly lower than in mice fed the CO diets (p < 0.0001). The levels of vitamin E did not affect the production of RANTES and JE/MCP-1. The levels of vitamin E had a significant effect on MIP-1alpha as the spleen cells of mice fed diets containing 694 IU/kg diet of vitamin E produced significantly higher levels of MIP-1alpha compared to the group of mice fed the diets containing 269 IU of vitamin E (p < 0.0001). The data obtained from this study in MRL/lpr and MRL/++ mice suggest that FO diets containing omega-3 fatty acids are beneficial in decreasing the levels of certain pro-inflammatory chemokines (RANTES and MCP-1) thereby delaying the onset of and severity of autoimmune symptoms in MRL/lpr mouse model.     

Maternal dietary n-3 fatty acids alter cardiac ventricle fatty acid composition, prostaglandin and thromboxane production in growing chicks

The effects of feeding n-6 and n-3 fatty acids to broiler hens on cardiac ventricle fatty acid composition, and prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) production of hatched chicks were investigated. Fertile eggs obtained from hens fed diets supplemented with 3.5% sunflower oil (Low n-3), 1.75% sunflower+1.75% fish oil (Medium n-3), or 3.5% fish oil (High n-3) were incubated. The hatched chicks were fed a diet containing 18:3 n-3, but devoid of longer chain n-6 and n-3 fatty acids for 42 days. Arachidonic acid content was lower in the cardiac ventricle of High n-3 and Medium n-3 compared to Low n-3 birds for up to 2 weeks (P<0.002). Long chain n-3 fatty acids were higher in the cardiac ventricle of chicks from hens fed High and Medium n-3 diets when compared to chicks from hens fed the Low n-3 diet. Differences in long chain n-3 fatty acids persisted up to four weeks of age (P<0.001). Peripheral blood mononuclear cells (PBMNC) of 7-day-old High n-3 broilers produced significantly lower PGE2 and TXA2 than PBMNC from Low n-3 and Medium n-3 birds. These results indicate that maternal dietary n-3 fatty acids increases cardiac ventricle n-3 fatty acids while reducing arachidonic acid and ex vivo PGE2 and TXA2 production during growth in broiler chickens.     

Uteroplacental production of eicosanoids in ovine pregnancy

Dramatic cardiovascular alterations occur during normal ovine pregnancy which may be associated with increased prostaglandin production, especially of uteroplacental origin. To study this, we examined (Exp 1) the relationships between cardiovascular alterations, e.g., the rise in uterine blood flow and fall in systemic vascular resistance, and arterial concentrations of prostaglandin metabolites (PGEM, PGFM and 6-keto-PGF1 alpha) in nonpregnant (n = 4) and pregnant (n = 8) ewes. To determine the potential utero-placental contribution of these eicosanoids in pregnancy, we also studied (Exp 2) the relationship between uterine blood flow and the uterine venous-arterial concentration differences of PGE2, PGF2 alpha, PGFM, 6-keto-PGF1 alpha, and TxB2 in twelve additional late pregnant ewes. Pregnancy was associated with a 37-fold increase in uterine blood flow and a proportionate (27-fold) fall in uterine vascular resistance (p less than 0.01). Arterial concentrations of PGEM were similar in nonpregnant and pregnant ewes (316 +/- 19 and 245 +/- 38 pg/ml), while levels of PGFM and PGI2 metabolite 6-keto-PGF1 alpha were elevated 23-fold (31 +/- 14 to 708 +/- 244 pg/ml) and 14-fold (12 +/- 4 to 163 +/- 78 pg/ml), respectively (p less than 0.01). Higher uterine venous versus uterine arterial concentrations were observed for PGE2 (397 +/- 36 and 293 +/- 22 pg/ml) and 6-keto-PGF1 alpha (269 +/- 32 and 204 +/- 32 pg/ml), p less than 0.05, but not PGF2 alpha or TxB2. Although PGFM concentrations appeared to be greater in uterine venous (1197 +/- 225 pg/ml) as compared to uterine arterial (738 +/- 150 pg/ml) plasma, this did not reach significance (0.05 less than p less than 0.1). In normal ovine pregnancy arterial levels of PGI2 are increased, which may in part reflect increased uteroplacental production. Moreover the gravid ovine uterus also appears to produce PGE2 and metabolize PGF2 alpha.     

Dietary fatty acid composition affects the repeat swimming performance of Atlantic salmon in seawater

Repeated critical swimming performance trials (Ucrit) were performed on Atlantic salmon (Salmo salar) to test the null hypothesis that the source of dietary lipids (fish-based, poultry-based, and plant-based) does not influence exercise and recovery performance. Four diets were prepared by extensively replacing supplemental lipid from anchovy oil (AO; 100% AO at 150 g/kg) with cold pressed flaxseed oil (FO; 25% AO, 75% FO), sunflower oil (SO; 25% AO, 75% SO), or poultry fat (PF; 25% AO, 75% PF). These diets had equivalent protein and energy concentrations, but due to the different supplemental lipid sources, varied widely in their fatty acid composition. Fish fed AO had a significantly higher (P<0.05) first Ucrit (2.62+/-0.07 body lenght s(-1)) than those fed PF (2.22+/-0.12 body lenght s(-1)) that had low muscle ratios of n-3 highly unsaturated fatty acids (n-3 HUFA) to saturated fatty acids (SFA) and arachidonic acid (AA), and high levels of oleic acid. Fish in the FO and SO diet groups swam as well as AO-fed fish in both swimming trials. The performance of fish fed AO decreased significantly (P<0.05) during the second swimming trial (i.e. Ucrit2/Ucrit1=0.92+/-0.02). No significant differences occurred between diet groups for the second swim trial. There was a positive correlation between both n-3 HUFA/SFA and n-3 HUFA/AA ratios, and Ucrit1. A negative correlation was found between dietary AA and oleic acids, and Ucrit1. The present study suggests that low dietary n-3 HUFA/ SFA and n-3 HUFA/AA ratios may negatively affect swimming performance. The former possibly can be offset by increasing linoleic acid in the presence of nutritionally adequate n-3 HUFA (e.g. SO diet). Lipid supplements consisting largely of vegetable oils did not compromise fish cardiorespiratory physiology under the conditions of this study.     

Reduced inflammatory response in rats fed fat-rich diets: role of leukotrienes

The effect of fat-rich diets on the acute inflammatory response was examined. Male Wistar rats aged 21 days were fed, for 6 weeks, with a control diet (4% fat content), or a control diet supplemented with coconut or soybean oils (15% fat content). Carrageenan-induced paw oedema and pleurisy were evaluated. Prostaglandin (PG) E2 and leukotriene (LT) C4/D4 concentrations were determined in the pleural exudate (ELISA). Pleural samples were tested for their effect on cutaneous vascular permeability of control rats and the effect of a LTD4 receptor antagonist (L660-711; 10 mg/kg; i.v.) examined. Relative to controls, rats fed both fat-rich diets presented a significant reduction in protein leakage and oedema formation without affecting the number of migrating leukocytes. Production of LTC4/D4 in pleural exudate was significantly increased from 1.8 +/- 0.2 ng/ml in controls to 2.8 +/- 0.2 and 3.0 +/- 0.3 ng/ml in animals fed coconut and soybean oil enriched diets, respectively, without changes in PGE2 production. The activity of these samples on cutaneous vascular permeability was 50% reduced, returning to control values after treatment of testing animals with a LTD4 receptor antagonist. Rats fed fat-rich diets presented a reduced inflammatory response due, at least in part, to the LTC4/D4 mediated vasoconstrictor effect.     

Activation state alters the effect of dietary fatty acids on pro-inflammatory mediator production by murine macrophages

Studies investigating the effect of dietary fats on pro-inflammatory cytokine production by macrophages (M phis) have yielded conflicting results. We hypothesised that this may be due to the different capacities of the M phis studied commonly (resident, thioglycollate-elicited) to produce prostaglandin E(2)(PGE(2)) and leukotriene B(4)(LTB(4)) which inhibit and stimulate, respectively, tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) production. To investigate this, male C57Bl6 mice were fed for 6 weeks on a low fat (LF) diet or on high fat diets which contained coconut oil (CO), olive oil (OO), safflower oil (SO) or fish oil (FO) as the main fat source. Production of TNF-alpha, IL-1 beta, PGE(2)and LTB(4)by lipopolysaccharide-stimulated resident and thioglycollate-elicited (i.e. inflammatory) peritoneal M phis was measured. PGE(2)production by both inflammatory and resident M phis was significantly decreased by FO feeding. FO also decreased LTB(4)production by resident M phis compared with LF feeding. Production of both cytokines by inflammatory M phis decreased with increasing unsaturation of the high fat diets, such that cells from FO-fed mice showed significantly decreased production of TNF-alpha and IL-1 beta compared to those from mice fed on each of the other diets. In contrast, resident M phis from mice fed FO showed increased TNF-alpha production compared to those from CO-fed mice. Thus, FO feeding decreases production of TNF-alpha and IL-1 beta by inflammatory M phis and increases production of TNF-alpha by resident M phis, at least in comparison to some other dietary fats. These results indicate the mechanisms by which dietary fats exert their effects upon pro-inflammatory cytokine production are most likely different for resident and inflammatory M phis.     

Enhanced plasma IL-6 and IL-1ra responses to repeated vs. single bouts of prolonged cycling in elite athletes.

The impact of repeated bouts of exercise on plasma levels of interleukin (IL)-6 and IL-1 receptor antagonist (IL-1ra) was examined. Nine well-trained men participated in four different 24-h trials: Long [two bouts of exercise, at 0800-0915 and afternoon exercise (Ex-A), separated by 6 h]; Short (two bouts, at 1100-1215 and Ex-A, separated by 3 h); One (single bout performed at the same Ex-A as second bout in prior trials); and Rest (no exercise). All exercise bouts were performed on a cycle ergometer at 75% of maximal O(2) uptake and lasted 75 min. Peak IL-6 observed at the end of Ex-A was significantly higher in Short (8.8 +/- 1.3 pg/ml) than One (5.2 +/- 0.7 pg/ml) but not compared with Long (5.9 +/- 1.2 pg/ml). Peak IL-1ra observed 1 h postexercise was significantly higher in Short (1,774 +/- 373 pg/ml) than One (302 +/- 53 pg/ml) but not compared with Long (1,276 +/- 451 pg/ml). We conclude that, when a second bout of endurance exercise is performed after only 3 h of recovery, IL-6 and IL-1ra responses are elevated. This may be linked to muscle glycogen depletion.     

Nutritional evaluation of structured lipid containing omega 6 fatty acid synthesized from coconut oil in rats

Coconut oil is rich in medium chain fatty acids, but deficient in polyunsaturated fatty acids (PUFA). Structured lipids (SL) enriched with omega 6 PUFA were synthesized from coconut oil triglycerides by employing enzymatic acidolysis with free fatty acids obtained from safflower oil. Rats were fed a diet containing coconut oil, coconut oil-safflower oil blend (1:0.7 w/w) or structured lipid at 10% levels for a period of 60 days. The SL lowered serum cholesterol levels by 10.3 and 10.5% respectively in comparison with those fed coconut oil and blended oil. Similarly the liver cholesterol levels were also decreased by 35.9 and 26.6% respectively in animals fed structured lipids when compared to those fed on coconut oil or the blended oil. Most of the decrease observed in serum cholesterol levels of animals fed structured lipids was found in LDL fraction. The triglyceride levels in serum showed a decrease by 17.5 and 17.4% while in the liver it was reduced by 45.8 and 23.5% in the structured lipids fed animals as compared to those fed coconut oil or blended oil respectively. Differential scanning calorimetric studies indicated that structured lipids had lower melting points and solid fat content when compared to coconut oil or blended oils. These studies indicated that enrichment of coconut oil triglycerides with omega 6 fatty acids lowers its solid fat content. The omega 6 PUFA enriched structured lipids also exhibited hypolipidemic activity.     

Does supplementation of formula with evening primrose and fish oils augment long chain polyunsaturated fatty acid status of low birthweight infants to that of breast-fed counterparts?

We investigated whether formulae with evening primrose and fish oils raise long chain polyunsaturated fatty acids (LCPUFA) in plasma cholesterol esters (CE), erythrocytes (RBC) and platelets (PLT) to levels encountered in breast-fed infants. Low birthweight infants (< or =2500 g) received LCP1 formula (n = 16; 0.31% 18:3 omega6, 0.17% 20:5 omega3 and 0.20% 22:6 omega3) or LCP2 formula (n = 13; 0.32% 18:3 omega6, 0.34% 20:5 omega3 and 0.43% 22:6 omega3). Fatty acids were measured days 10+/-2, 20+/-3 and 42+/-3. The formulae raised CE, RBC and PLT 20:5 omega3 and 22:6 omega3 dose-dependently (P<0.01), to exceed levels of breast-fed babies (n = 18) day 42 (P<0.05). CE, RBC and PLT 20:3 omega6 was comparable with, and CE, RBC, PLT 20:4 omega6 were below, that of breast-fed infants (P<0.05). Dietary 20:5 omega3 and 22:6 omega3 related with CE, RBC and PLT 20:5 omega3 and 22:6 omega3 (n = 47; P< or =0.01). Dietary 20:5 omega3 and LCPUFA omega3 related inversely with CE, RBC and PLT 20:4 omega6 and LCPUFA omega6 (P< or =0.002). LCP1 and LCP2 fed infants had similar LCPUFA omega6 status day 42. Added 18:3 omega6 does not correct 20:4 omega6 to that of breast-fed infants, but improves 20:3 omega6 status. Fish oil dose-dependently raises 20:5 omega3 and 22:6 omega3, but decreases 20:4 omega6 and other LCPUFA omega6.     

Effect of long-term feeding olive and sunflower oils on fatty acid composition and desaturation activities of liver microsomes

Changes in microsomal fatty acid composition, delta 9- and delta 6-desaturase activities and cholesterol and phosphorus liver content were studied in dogs fed olive and sunflower oil diets. No changes were observed in the saturated fatty acids between dietary groups. The level of monounsaturated fatty acids was more elevated in animals fed the OO diet, because of its high relative content in this diet although the in vitro delta 9-desaturase activity was similar in microsomes from the two groups. The proportion of arachidonic acid was similar in SO and OO fed animals. This similar level occurred despite a significant increase in the level of linoleic acid in membrane lipids as a result of feeding the SO supplement. The in vitro delta 6-desaturase activity in liver microsomes showed no differences between dogs fed the two diets. Thus, the higher desaturation presented in vivo by microsomes from OO group may be related to the inhibition by linoleic acid of delta 6-desaturase in dogs fed the SO diet. The polyunsaturated fatty acids (PUFA) from the n-3 series were higher in microsomal phosphatidylcholine and phosphatidylethanolamine from animals fed the OO supplemented diet. The cholesterol/phosphorus molar ratio was higher in the SO group in which the unsaturation index was only slightly affected in phospholipids.     

Influence of an increased intake of linoleic acid on the incorporation of dietary (n-3) fatty acids in phospholipids and on prostanoid synthesis in rat tissues.

We investigated whether the amount of dietary linoleic acid (LA) (as corn oil) influences the incorporation of dietary eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) in tissue phospholipids and the prostanoid biosynthesis. Rats were fed four different levels of corn oil (at a total dietary fat level of either 2.5%, 5%, 10% or 20%); at each corn oil level, two groups of rats were supplemented with either EPA and DHA (200 mg/day) during 6 weeks, and compared with a group receiving oleic acid. The phospholipid fatty acid composition of liver, kidney and aorta showed, as expected, that the incorporation of EPA was highly suppressed by increasing the content of dietary linoleic acid in the diets. On the other hand, DHA was almost unaffected by the amounts of (n - 6) fatty acids in the diets. These results indicate that EPA levels but not DHA levels in tissue phospholipids were influenced by the competing dietary (n - 6) fatty acids. The tissue arachidonate content was similar under the various dietary linoleic acid conditions, but feeding EPA or DHA lowers the AA content. Moreover, the amount of dietary linoleic acid did not significantly influence the prostaglandin E2 (PGE2) production in stimulated aortic rings. However, PGE2 synthesis was significantly decreased in the groups treated with either EPA or DHA. Thromboxane B2 levels in serum followed a similar pattern. It is suggested that an increase of dietary (n - 3) PUFAs is more efficient to reduce (n - 6) eicosanoid formation than a decrease of dietary (n - 6) fatty acids.     

High altitude increases circulating interleukin-6, interleukin-1 receptor antagonist and C-reactive protein

Hypoxic pulmonary vasoconstriction is associated with but may not be sufficient for the development of high-altitude pulmonary oedema (HAPO). Hypoxia is known to induce an inflammatory response in immune cells and endothelial cells. It has been speculated that hypoxia-induced inflammatory cytokines at high altitude may contribute to the development of HAPO by causing capillary leakage in the lung. We were interested if such an inflammatory response, possibly involved in a later development of HAPO, is detectable at high altitude in individuals without HAPO. We examined the plasma levels of interleukin 6 (IL-6), interleukin 1 receptor antagonist (IL-1ra) and C-reactive protein (CRP) in two independent studies: study A, Jungfraujoch, Switzerland, three overnight stays at 3458 m, n=12; study B: Capanna Regina Margherita, Italy, 3 overnight stays at 3647 m and one overnight stay at 4559 m, n=10. In both studies, probands showed symptoms of acute mountain sickness but no signs of HAPO. At the Jungfraujoch, IL-6 increased from 0.1+/-0.03 pg/ml to 2. 0+/-0.5 pg/ml (day 2, P=0.03), IL-1ra from 101+/-21 to 284+/-73 pg/ml (day 2, P=0.01), and CRP from 1.0+/-0.4 to 5.8+/-1.5 micrograms/ml (day 4, P=0.01). At the Capanna Margherita, IL-6 increased from 0. 5+/-0.2 pg/ml to 2.0+/-0.8 pg/ml (P=0.02), IL-1ra from 118+/-25 to 213+/-28 pg/ml (P=0.02), and CRP from 0.4+/-0.03 to 3.5+/-1.1 micrograms/ml (P=0.03). IL-8 was below the detection limit of the ELISA (<25 pg/ml) in both studies. The increase of IL-6 and IL-1ra in response to high altitude was delayed and preceded the increase of CRP. We conclude that: (1) circulating IL-6, IL-1ra and CRP are upregulated in response to hypobaric hypoxic conditions at high altitude, and (2) the moderate systemic increase of these inflammatory markers may reflect considerable local inflammation. The existence and the kinetics of high altitude-induced cytokines found in this study support the hypothesis that inflammation is involved in the development of HAPO.     

Dietary coconut oil increases conjugated linoleic acid-induced body fat loss in mice independent of essential fatty acid deficiency

Conjugated linoleic acid (CLA) induces a body fat loss that is enhanced in mice fed coconut oil (CO), which lacks essential fatty acids (EFA). Our objective was to determine if CO enhancement of CLA-induced body fat loss is due to the lack of EFA. The CLA-EFA interaction was tested by feeding CO and fat free (FF) diets for varying times with and without replenishment of individual EFA. Mice fed CO during only the 2-week CLA-feeding period did not differ from control mice in their adipose EFA content but still tended (P=0.06) to be leaner than mice fed soy oil (SO). Mice raised on CO or FF diets and fed CLA were leaner than the SO+CLA-fed mice (P<0.01). Mice raised on CO and then replenished with linoleic, linolenic, or arachidonic acid were leaner when fed CLA than mice raised on SO (P<0.001). Body fat of CO+CLA-fed mice was not affected by EFA addition. In summary, CO-fed mice not lacking in tissue EFA responded more to CLA than SO-fed mice. Also, EFA addition to CO diets did not alter the enhanced response to CLA. Therefore, the increased response to CLA in mice raised on CO or FF diets appears to be independent of a dietary EFA deficiency.     

The role of interleukin 6 in interferon-gamma production in thermally injured mice

Following traumatic injury, patients suffer from compromised immunity increasing their susceptibility to infection. Previous studies from this laboratory demonstrated that female BALB/c mice subjected to a 15% total body surface area (TBSA) scald injury exhibit a decrease in cell-mediated immunity 10 days post-burn. Studies described herein revealed that concanavalin A (Con A; 2 microg/ml)-stimulated splenocytes from sham treated animals produced 3557+/-853 pg/ml of IFN-gamma while splenocytes from burn injured animals released two-fold more cytokine (P<0.05). To determine whether leukocyte production of IFN-gamma was under the influence of macrophages, splenic macrophage supernatants generated from burned animals were incubated with splenic lymphocytes from sham and burn animals. The amount of IFN-gamma released by lymphocytes from sham animals increased when cultured with macrophages from burned mice (P<0.05). This suggests that the increase in IFN-gamma production by unfractionated splenocytes in burned mice relative to sham treated animals is macrophage-dependent. Macrophage supernatants from burned mice released twice as much IL-6 as supernatants from sham animals (P<0.05), and when IL-6 was blocked in vivo, the amount of IFN-gamma production in burned mice decreased to sham levels (P<0.05). Thus, IL-6 mediates IFN-gamma production following burn.