Polyunsaturated fats,membrane lipids and animal longevity

Fatty acids are essential for life because they are essential components of cellular membranes. Lower animals can synthesize all four classes of fatty acids from non-lipid sources, but both omega-6 and omega-3 cannot be synthesized de novo by ‘higher’ animals and are therefore essential components of their diet. The relationship between normal variation in diet fatty acid composition and membrane fatty acid composition is little investigated. Studies in the rat show that, with respect to the general classes of fatty acids (saturated, monounsaturated and polyunsaturated) membrane fatty acid composition is homeostatically regulated despite diet variation. This is not the case for fatty acid composition of storage lipids, which responds to diet variation. Polyunsaturated fatty acids are important determinants of physical and chemical properties of membranes. They are the substrates for lipid peroxidation and it is possible to calculate a peroxidation index (PI) for a particular membrane composition. Membrane PI appears to be homeostatically regulated with respect to diet PI. Membrane fatty acid composition varies among species and membrane PI is inversely correlated to longevity in mammals, birds, bivalve molluscs, honeybees and the nematode Caenorhabditis elegans.     

Association between Ω3 and Ω6 fatty acid intakes and serum inflammatory markers in COPD

Dietary intake of polyunsaturated fatty acids, including omega-3 and omega-6, could modulate chronic obstructive pulmonary disease (COPD) persistent inflammation. We aimed to assess the relationship between dietary intake of omega-3 and omega-6 fatty acids and serum inflammatory markers in COPD. A total of 250 clinically stable COPD patients were included. Dietary data of the last 2 years were assessed using a validated food frequency questionnaire (122 items), which provided levels of three omega-3 fatty acids: docosahexaenoic acid, eicosapentaenoic acid and α-linolenic acid (ALA); and two omega-6 fatty acids: linoleic acid and arachidonic acid (AA). Inflammatory markers [C-reactive protein (CRP), interleukin (IL)-6, IL-8 and tumor necrosis factor alpha (TNFα)] were measured in serum. Fatty acids and inflammatory markers were dichotomised according to their median values, and their association was assessed using multivariate logistic regression. Higher intake of ALA (an anti-inflammatory omega-3 fatty acid) was associated with lower TNFα concentrations [adjusted odds ratio (OR)=0.46; P=.049]. Higher AA intake (a proinflammatory omega-6 fatty acid) was related to higher IL-6 (OR=1.96; P=.034) and CRP (OR=1.95; P=.039) concentrations. Therefore, this study provides the first evidence of an association between dietary intake of omega-3 and omega-6 fatty acids and serum inflammatory markers in COPD patients.     

Fatty acid composition of the postmortem prefrontal cortex of adolescent male and female suicide victims

Prior epidemiological, prospective intervention, and peripheral and central fatty acid composition studies suggest that omega-3 fatty acid deficiency may be associated with the pathoaetiology of depression and suicide. In the present study, we determined the fatty acid composition of the postmortem prefrontal cortex (PFC) of adolescent male and female suicide victims and age-matched controls. Fatty acid composition (wt% total fatty acids) and concentrations (μmol/g) were determined in the postmortem PFC (Brodmann area 10) of male and female adolescent (aged 13–20 years) suicide victims (n=20) and age-matched controls (n=20) by gas chromatography. None of the major polyunsaturated fatty acids including the principle brain omega-3 fatty acid, docosahexaenoic acid (DHA), monounsaturated fatty acids, or saturated fatty acids differed significantly between adolescent suicide victims and controls before or after segregation by gender. The arachidonic acid (AA, 20:4n-6): DHA ratio and adrenic acid (22:4n-6) composition were negatively correlated with age at death in controls but not in suicides, and males exhibited a greater AA:DHA ratio irrespective of cause-of-death. These results demonstrate that adolescent male and female suicide victims do not exhibit DHA deficits in the postmortem PFC relative to age-matched controls, and suggest that suicide victims do not exhibit the normal age-related decrease in adrenic acid composition and the AA:DHA ratio.     

Marked depression of radiation-induced emesis in frogs following prior exposure to a brief dose of X-rays

Acute emesis response to harmful doses of X-rays on frogs (Rana porosa porosa) was examined. Results showed that the number of radioemesis events following exposure to 0.85 Gy was slightly higher than in the sham control animals. The increase in emesis action became more pronounced when the total dose of radiation was raised to 2.5 Gy. Only 1 frog out of a total of 12 did not show vomiting following radiation, while no response was observed in sham control animals. Note that animals in which the low dose rate of radiation was applied to whole body did not display any changes in the emesis response relative to control animals. The present studies, and those by others, showed that a brief dose of X-rays prior to a second exposure to a sub-lethal dose might induce a tolerance to radiation. An additional experiment was conducted to examine whether a small conditioning dose could induce a depression of radioemesis (tolerance) following an exposure to high dose X-ray. With prior exposure to 0.3 Gy, only 1 frog out of a total of 5 frogs vomited as a result of radiation exposure. Suppression of the emetic response became significant when the pre-radiation dose was decreased to 0.1 Gy. On the contrary, increasing the small conditioning dose to 0.5 Gy resulted in a remarkable rise of radiation-induced emesis. This results indicate that exposure to the smaller dose of X-rays elicits a tolerance effect to toxic dose level of radiation.     

Ethanol sensitivity and fatty acid composition of chick liver mitochondrial and microsomal membranes

Fatty acid composition of hepatic mitochondrial and microsomal membranes was studied in 2-day-old chicks exposed to ethanol for 60 h (short treatment) or 18 days (chronic treatment). Short ethanol treatment induced in mitochondria an increase in the 18:1/18:0 ratio as a consequence of both an increase in the percentage of oleic and a decrease in that of stearic acid. Likewise, a clear decrease in the polyunsaturated fatty acids and in the 20:4/18:2 ratio was found in mitochondria after short ethanol administration. Microsomal membranes were practically unaffected by this treatment. However, chronic ethanol exposure produced a significant increase in the percentages of polyunsaturated fatty acids in both mitochondria and microsomes as well as a decrease in the 18:1/18:0 ratio. These results suggest that delta 9 desaturase modifies its activity in response to ethanol treatment with a different pattern to those showed by delta 6 and delta 5 desaturase activities.     

Heterotrophic production of long chain omega-3 fatty acids utilizing algae and algae-like microorganisms

Although some interest in growing microalgae heterotrophically for the production of pigments was generated in the 1960s, only minimal commercial research was focused on this type of production technology until the 1980s. Recent developments indicating the nutritional and pharmaceutical importance of long chain omega-3 polyunsaturated fatty acids in the human diet have stimulated interest in microalgae as a source of these vital compounds, for they are the primary producers of these fatty acids in marine food webs. Food and pharmaceutical quality production can be enhanced both by the degree of process control and by the sterility achieved through a fermentation process, when compared to outdoor solar pond production. The data presented illustrate that microalgal-based heterotrophic production systems can exhibit omega-3 fatty acid productivities 2–3 orders of magnitude greater than those of outdoor pond systems. Additionally, long chain omega-3 fatty acid productivities reported for the microalgal fermentation systems are 1–2 orders of magnitude greater than productivities reported for fungal or bacterial systems.     

Lipid content and composition in common carp – optimization of n‐3 fatty acids in different pond production systems

This study examined whether the lipid composition of common carp muscle can be improved and become an important source of n‐3 highly unsaturated fatty acids (HUFA) in human nutrition. Carp from three pond production systems in South Bohemia were given access to plankton, plankton with the addition of cereals, or pellets containing rapeseed cake suggested to enhance lipid nutritional value. White muscle fatty acid composition was investigated and compared among treatments. Fish with no supplements were characterized by a high content of n‐3 HUFA, especially eicosapentaenoic (EPA) and docosahexaenoic acid (DHA). Fish supplemented with rapeseed pellets had a moderate n‐3 HUFA level, while those supplemented with cereals were characterized by a high oleic acid content and low level of n‐3 fatty acids. The pond plankton populations contained high proportions of n‐3 fatty acids, including EPA and DHA, with an n‐3/n‐6 ratio around three. In summary, the rapeseed‐based pellet resulted in a more polyunsaturated lipid composition of the fish flesh, also with regard to n‐3 fatty acids. The conclusion is that the novel rapeseed‐based supplement is beneficial to human health.     

Changes in the fatty acid composition of steelhead trout, Salmo gairdnerii Richardson, associated with parr-smolt transformation

Fatty acids from the several lipid classes of selected steelhead trout (Salmo gairdnerii) parr and smolt tissues, previously separated by thin-layer chromatography, were analyzed by gas-liquid chromatography. The fatty acid composition of the parr was markedly different from that of the smolt; the former being characterized by relatively low amounts of polyunsaturated fatty acids and relatively high amounts of linoleic acid, much like the typical freshwater lipid pattern. The fatty acid composition of the smolt was characterized by large proportions of long-chain polyunsaturated fatty acids. Generally, the fatty acid composition of the smolt resembled the typical seawater lipid pattern. The change in fatty acid composition of the smolt is anticipatory to seawater entry and is independent of diet and water temperature. These alterations suggest that the assumption of a polyunsaturated lipid pattern during parr-smolt transformation (smoltification) is preadaptive to seawater entry.     

Low-dose total-body γ irradiation modulates immune response to acute proton radiation

Health risks due to exposure to low-dose/low-dose-rate radiation alone or when combined with acute irradiation are not yet clearly defined. This study quantified the effects of protracted exposure to low-dose/low-dose-rate γ rays with and without acute exposure to protons on the response of immune and other cell populations. C57BL/6 mice were irradiated with ??Co (0.05 Gy at 0.025 cGy/h); subsets were subsequently exposed to high-dose/high-dose-rate proton radiation (250 MeV; 2 or 3 Gy at 0.5 Gy/min). Analyses were performed at 4 and 17 days postexposure. Spleen and thymus masses relative to body mass were decreased on day 4 after proton irradiation with or without pre-exposure to γ rays; by day 17, however, the decrease was attenuated by the priming dose. Proton dose-dependent decreases, either with or without pre-exposure to γ rays, occurred in white blood cell, lymphocyte and granulocyte counts in blood but not in spleen. A similar pattern was found for lymphocyte subpopulations, including CD3+ T, CD19+ B, CD4+ T, CD8+ T and NK1.1+ natural killer (NK) cells. Spontaneous DNA synthesis by leukocytes after proton irradiation was high in blood on day 4 and high in spleen on day 17; priming with γ radiation attenuated the effect of 3 Gy in both body compartments. Some differences were also noted among groups in erythrocyte and thrombocyte characteristics. Analysis of splenocytes activated with anti-CD3/anti-CD28 antibodies showed changes in T-helper 1 (Th1) and Th2 cytokines. Overall, the data demonstrate that pre-exposure of an intact mammal to low-dose/low-dose-rate γ rays can attenuate the response to acute exposure to proton radiation with respect to at least some cell populations.     

Myeloid progenitors: a radiation countermeasure that is effective when initiated days after irradiation

The aim of this study was to elucidate the potential of mouse myeloid progenitor cells (mMPC) to mitigate lethal doses of (60)Co γ radiation and X rays in various strains of mice. Different cell doses of pooled allogeneic mMPC generated ex vivo from AKR, C57Bl/6, and FVB mice were transfused intravenously into haplotype-mismatched recipient Balb/c or CD2F1 mice at various times after irradiation to assess their effect on 30-day survival. Our results show that cryopreserved allogeneic mMPC significantly improve survival in both strains of mice irradiated with lethal doses of (60)Co γ radiation (CD2F1, 9.2 Gy) and X-ray exposures (Balb/c, 9 Gy) that are known to cause acute radiation syndrome in hematopoietic tissues. Survival benefit was mMPC-dose dependent and significant even when mMPC administration was delayed up to 7 days after irradiation. We further show that mMPC administration mitigates death from acute radiation syndrome at radiation doses of up to 15 Gy ((60)Co γ radiation, CD2F1), which are radiation exposure levels that cause mice to succumb to multi-organ failure, and determined that the dose-reduction factor of 5 million mMPC administered 24 h after irradiation of CD2F1 mice is 1.73. Even at high doses of up to 14 Gy (60)Co γ radiation, mMPC administration could be delayed up to 5 days in CD2F1 mice and still provide significant benefit to 30-day survival. These results demonstrate that mMPC are a promising radiation countermeasure with the potential to mitigate radiation injury in unmatched recipients across a broad range of lethal radiation doses, even when administration is delayed days after radiation exposure. With respect to efficacy, timing, and practicality of administration, mMPC appear to be a very promising radiation countermeasure for acute radiation syndrome among all candidate therapeutics currently under development.     

Analysis of white blood cell counts in mice after gamma- or proton-radiation exposure

In the coming decades human space exploration is expected to move beyond low-Earth orbit. This transition involves increasing mission time and therefore an increased risk of radiation exposure from solar particle event (SPE) radiation. Acute radiation effects after exposure to SPE radiation are of prime importance due to potential mission-threatening consequences. The major objective of this study was to characterize the dose-response relationship for proton and γ radiation delivered at doses up to 2 Gy at high (0.5 Gy/min) and low (0.5 Gy/h) dose rates using white blood cell (WBC) counts as a biological end point. The results demonstrate a dose-dependent decrease in WBC counts in mice exposed to high- and low-dose-rate proton and γ radiation, suggesting that astronauts exposed to SPE-like radiation may experience a significant decrease in circulating leukocytes.     

Nutritional intervention with omega-3 fatty acids enhances tumor response to anti-neoplastic agents

Nutritional intervention with specific fatty acids depresses tumor growth and enhances tumor responsiveness to chemotherapy. Supplementation of tumors with long chained omega-3 polyunsaturated fatty acids results in enrichment of tumor phospholipid fractions with omega-3 fatty acids resulting in an altered membrane composition and function. Tumors enriched with long chained omega-3 polyunsaturated fatty acids possess membranes with increased fluidity, an elevated unsaturation index, enhanced transport capabilities that results in accumulation of selective anti-cancer agents, increased activity of selected drug activating enzymes, and alteration of signaling pathways important for cancer progression. These nutritionally induced changes in tumor fatty acid composition result in increased sensitivity to chemotherapy, especially in tumor lines that are resistant to chemotherapy and cause specific enhancement of cytotoxicity to tumor cells and protection of normal cells. Pre-disposing tumors to increased chemo-sensitivity through nutritional intervention with specific fatty acids has the potential to improve patient response to chemotherapy with fewer untoward side effects if these pre-clinical findings carry over into a clinical setting.     

The effects of a diet rich in docosahexaenoic acid on organ and vascular fatty acid composition in spontaneously hypertensive rats

Previous research has shown that dietary docosahexaenoic acid (DHA) attenuates the development of high blood pressure in young spontaneously hypertensive rats (SHR). The purpose of this study was to investigate the effects of dietary DHA on organ and vascular fatty acid composition in SHR. Given the important structural and functional role of fatty acids in cell membranes, alterations in fatty acid composition may contribute to the antihypertensive effect of DHA. SHR were fed a purified diet containing either a corn/soybean oil mixture (CSO, control) or a DHA-enriched oil for 6 weeks. The DHA diet markedly increased the levels of DHA in the aorta, renal artery, plasma, liver, heart, kidney, and lung by 5-, 15-, 7-, 6-, 3.8-, 3.5-, and 8.8-fold (P<0.001), respectively. The levels of eicosapentaenoic acid were also increased while there was a concomitant reduction in arachidonic and adrenic acids. Therefore, dietary DHA increases the incorporation of omega-3 polyunsaturated fatty acids in specific organs and vascular tissue in SHR at the expense of omega-6 polyunsaturated fatty acids.     

Omega-3 fatty acids differentially modulate enzymatic anti-oxidant systems in skeletal muscle cells

During physical activity, increased reactive oxygen species production occurs, which can lead to cell damage and in a decline of individual’s performance and health. The use of omega-3 polyunsaturated fatty acids as a supplement to protect the immune system has been increasing; however, their possible benefit to the anti-oxidant system is not well described. Thus, the aim of this study was to evaluate whether the omega-3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid) can be beneficial to the anti-oxidant system in cultured skeletal muscle cells. C2C12 myocytes were differentiated and treated with either eicosapentaenoic acid or docosahexaenoic acid for 24 h. Superoxide content was quantified using the dihydroethidine oxidation method and superoxide dismutase, catalase, and glutathione peroxidase activity, and expression was quantified. We observed that the docosahexaenoic fatty acids caused an increase in superoxide production. Eicosapentaenoic acid induced catalase activity, while docosahexaenoic acid suppressed superoxide dismutase activity. In addition, we found an increased protein expression of the total manganese superoxide dismutase and catalase enzymes when cells were treated with eicosapentaenoic acid. Taken together, these data indicate that the use of eicosapentaenoic acid may present both acute and chronic benefits; however, the treatment with DHA may not be beneficial to muscle cells.     

Proximate composition, fatty acid and lipid class composition of the muscle from deep-sea teleosts and elasmobranchs

Proximate composition of muscle was determined for the following deep-sea fish species: roughhead grenadier (Macrourus berglax), mora/deep-sea cod (Mora moro), Portuguese dogfish (Centroscymnus coelolepis), black dogfish (Centroscyllium fabricii), leafscale gulper shark (Centrophorus squamosus), greater lantern shark (Etmopterus princeps), smalleyed rabbitfish/ghostshark (Hydrolagus affinis), birdbeak dogfish (Deania calcea) and two species of smooth head (Alepocephalus bairdii and Alepocephalus agassizii). The first eight species contained less than 1% fat in the muscle, while the last two contained 3.0% and 3.6% fat, respectively. Fatty acid and lipid class composition was determined for the first five fish species and showed that the dominant class of lipids was phospholipids. The lipids consisted mainly of polyunsaturated fatty acids (PUFA), and docosahexaenoic acid (DHA) was the dominant fatty acid. Roughhead grenadier and mora showed resemblance to cod (Gadus morhua) regarding protein content, fat content and fatty acid composition. However, the muscle from the deep-sea fish species did contain a higher proportion of arachidonic acid (20:4n-6) than cod muscle.     

Fatty Acid Profiling of Commercially Important Raw and Boiled Seer Fish <Emphasis Type="Italic">Scomberomorus commerson</Emphasis> (Lacepede, 1800) (Scombridae,Teleostei, Pisces)

The present study aims to determine the fatty acid profiling of commercially important fresh and boiled Scomberomorus commerson. Fatty acids in fresh and boiled fish were separated and quantitatively determined by gas chromatography–mass spectrophotometer using standard methods. The findings revealed that the predominant fatty acids in fresh S. commerson were octadecanoic acid methyl ester, octanoic acid, 1,2-benzenedicarboxylic acid and 3-cyclopentylpropionic acid representing respectively 45.91, 5.69, 6.75 and 8.65% of total fatty acids. Boiled S. commerson showed predominant changes in their fatty acid profiles. In the omega-3 and omega-6 families the dominant fatty acids were doconexent, 3-cyclopentylpropionic acid, octadeconoic acid methyl ester and Hexadecane representing respectively 3.87, 12.08, 44.26 and 3.11% of total fatty acids. After boiling, some fatty acids present in fresh fish are damaged and formed new fatty acids which belonged to ω-3 polyunsaturated fatty acids (PUFA). Boiling increased the concentration of PUFAs from 73.25 to 80.37% of total fatty acids and also formed new fatty acids.     

Effect of long-chain fatty acids in the culture medium on fatty acid composition of WEHI-3 and J774A.1 cells

As a first step in determining the mechanism of action of specific fatty acids on immunological function of macrophages, a comparative study of the effect of long-chain polyunsaturated fatty acids (PUFA) in the medium was conducted in two macrophage cell lines, J774A.1 and WEHI-3. The baseline fatty-acid profiles of the two cell lines differed in the % distribution of saturated (SFA) and unsaturated fatty acids (UFA). J774A.1 cells had a higher % of SFA (primarily palmitic acid) than WEHI-3 cells. Conversely, WEHI-3 cells had a higher % of UFA (primarily oleic acid) than J774A.1 cells. Neither cell line had detectable amounts of alpha-linolenic acid (ALA) or eicosapentaenoic acid (EPA). The most abundant polyunsaturated fatty acid in both cells lines was arachidonic acid (AA). The efficiency of transport of fatty acids from the medium to the macrophages by two delivery vehicles (BSA complexes and ethanolic suspensions) was compared. Overall, fatty acids were transported satisfactorily by both delivery systems. Alpha-linolenic acid and doscosahexenoic acid (DHA) were transported more efficiently by the ethanolic suspension system. Linoleic acid (LA) was taken up more completely than ALA, and DHA was taken up more completely than EPA by both cell cultures and delivery systems. A dose-response effect was demonstrated for LA, ALA, EPA and DHA in both J774A.1 and WEHI-3 cells. Addition of polyunsaturated fatty acids (PUFA) to the cell cultures modified the total lipid fatty acid composition of the cells. The presence of ALA in the culture medium resulted in a significant decrease in AA in both cell lines. The omega-3/omega-6 fatty acid ratio (omega-3/omega-6), polyunsaturated/saturated fatty acid ratio (P/S), and unsaturation index (UI) increased directly with the amount of PUFA and omega-3 fatty acid provided in the medium. The results indicate that the macrophage cell lines have similar, but not identical, fatty acid profiles that may be the result of differences in fatty acid metabolism. These distinctions could in turn produce differences in immunological function. The ethanol fatty-acid delivery system, when compared with the fatty acid-BSA complex system, is preferable for measurement of dose-response effects, because the cellular fatty acid content increased in proportion to the amount of fatty acid provided in the medium. Similar dose-response results were observed in a previous in vivo study using flaxseed, rich in ALA, as a source of PUFA.     

Eicosanoids in skin inflammation

Eicosanoids play an integral part in homeostatic mechanisms related to skin health and structural integrity. They also mediate inflammatory events developed in response to environmental factors, such as exposure to ultraviolet radiation, and inflammatory and allergic disorders, including psoriasis and atopic dermatitis. This review article discusses biochemical aspects related to cutaneous eicosanoid metabolism, the contribution of these potent autacoids to skin inflammation and related conditions, and considers the importance of nutritional supplementation with bioactives such as omega-3 and omega-6 polyunsaturated fatty acids and plant-derived antioxidants as means of addressing skin health issues.     

Move that fatty acid: fuel selection and transport in migratory birds and bats

The metaphor of marathon running is inadequate to fully capture the magnitude of long-distance migratory flight of birds. In some respects a journey to the moon seems more appropriate. Birds have no access to supplementary water or nutrition during a multi-day flight, and they must carefully budget their body fat and protein stores to provide both fuel and life support. Fatty acid transport is crucial to successful non-stop migratory flight in birds. Although fat is the most energy-dense metabolic fuel, the insolubility of its component fatty acids makes them difficult to transport to working muscles fast enough to support the highly aerobic exercise required to fly. Recent evidence indicates that migratory birds compensate for this by expressing large amounts of fatty acid transport proteins on the membranes of the muscles (FAT/CD36 and FABPpm) and in the cytosol (H-FABP). Through endogenous mechanisms and/or diet, migratory birds may alter the fatty acid composition of the fat stores and muscle membranes to improve endurance during flight. Fatty acid chain length, degree of unsaturation, and placement of double bonds can affect the rate of mobilization of fatty acids from adipose tissue, utilization of fatty acids by muscles, and whole-animal performance. However, there is great uncertainty about how important fatty acid composition is to the success of migration or whether particular types of fatty acids (e.g., omega-3 or omega-6) are most beneficial. Migratory bats provide an interesting example of evolutionary convergence with birds, which may provide evidence for the generality of the bird model to the evolution of migration by flight in vertebrates. Yet only recently have attempts been made to study bat migration physiology. Many aspects of their fuel metabolism are predicted to be more similar to those of migrant birds than to those of non-flying mammals. Bats may be distinct from most birds in their potential to conserve energy by using torpor between flights, and in the behavioral and physiological trade-offs they may make between migration and reproduction, which often overlap.