Changes In Fatty Acid Composition Research Articles

Oxidative stability and characterization of oleogels obtained from safflower oil‐based beeswax and rice bran wax and their effect on the quality of cake samples

AbstractSafflower oil‐based oleogels were produced from beeswax and rice bran wax. Oleogels demonstrated higher oxidative stability than shortening at the cooking temperature. Peroxide values in shortening, rice bran wax oleogels, and beeswax oleogels samples were found in the range of 4.8–27.76, 13.21–20.45 and 4.30–7.72 meqO2kg−1 oil. Following oleogelation, there was no significant change in fatty acid composition of safflower oil. In addition, after baking process, the changes in the major fatty acids were not determined to be significant. Solid fat content ratios (carried out at 35°C) of rice bran wax oleogels, in beeswax oleogels and in shortening samples were defined in the range of 4.10%–7.70%, 0.80%–5.00%, and 9.61%, respectively. The highest oil binding capacity was revealed in beeswax oleogels with 99.93%–99.98%. The shortest crystallization time was determined as 3 min in oleogel containing 10% rice bran wax. Cakes consisted of oleogel were acceptable in terms of texture and sensory properties compared to cake produced with shortening. Sensory results revealed that some cakes produced with oleogels were found to be more acceptable as compared with control group samples. In this respect, oleogels produced with safflower oil‐based beeswax and rice bran wax could be used instead of commercial solid fat widely used in the cake industry.

Zinc- and nickel-induced changes in fatty acid profiles in the zinc hyperaccumulator Arabidopsis halleri and non-accumulator Arabidopsis lyrata

This pilot study aimed at comparing zinc (Zn) and nickel (Ni) effects on the fatty acid (FA) profiles, oxidative stress and desaturase activity in the Zn hyperaccumulator Arabidopsis halleri and the excluder Arabidopsis lyrata to allow a better picture of the physiological mechanisms which may contribute to metal tolerance or acclimation. The most significant changes in the FA composition were observed in the shoots of the hyperaccumulator and in the roots of the excluder, and were not only metal-dependent, but also species-specific, since the most significant changes in the shoots of A. halleri were observed under Ni treatment, though Ni, in contrast to Zn, was accumulated mainly in its roots. Several FAs appeared in the roots and shoots of A. lyrata only upon metal exposure, whereas they were already found in control A. halleri. In both species, there was an increase in oleic acid under Ni treatment in both organs, whereas in Zn-treated plants the increase was shown only for the shoots. A rare conjugated α-parinaric acid was identified only in the shoots of metal-treated A. halleri. In the shoots of the hyperaccumulator, there was an increase in the content of saturated FAs and a decrease in the content of unsaturated FAs, while in the roots of the excluder, the opposite pattern was observed. These metal-induced changes in FA composition in the shoots of A. halleri can lead to a decrease in the fluidity of membranes, which could diminish the penetration of ROS into the membrane and thus maintain its stability.

Changes in physicochemical, microbiological and fatty acid composition during the ripening period of artisan sheep cheese from Bulgaria

The composition of artisan sheep's milk cheese during the ripening period was studied. The raw material used for cheese production, was obtained from an indigenous Karakachan sheep from Bulgaria. It was found that the main physicochemical parameters of the cheese have changed during the study period. During the ripening process, chaaracteristics such as dry matter, total protein and fat content increased by approximately 7.0%, 3.0% and 4.0% respectively, while the water content of the samples decreased by up to 7.0%. A smooth acidification process was observed, which correlated with the high number of lactic acid bacteria. The fatty acid analysis showed that the saturated fatty acid composition was 66.0% and unsaturated fatty acids were 34.0%. During the biochemical ripening at the 60th day of the test period, the presence of linoleic polyunsaturated fatty acid was found to be 0.12%.

Effect of omega-3 ethyl esters on the triglyceride-rich lipoprotein response to endotoxin challenge in healthy young men

Oxylipins are produced enzymatically from polyunsaturated fatty acids, are abundant in triglyceride-rich lipoproteins (TGRLs), and mediate inflammatory processes. Inflammation elevates TGRL concentrations, but it is unknown if the fatty acid and oxylipin compositions change. In this study, we investigated the effect of prescription ω-3 acid ethyl esters (P-OM3; 3.4 g/d EPA + DHA) on the lipid response to an endotoxin challenge (lipopolysaccharide; 0.6 ng/kg body weight). Healthy young men (N = 17) were assigned 8–12 weeks of P-OM3 and olive oil control in a randomized order crossover study. Following each treatment period, subjects received endotoxin challenge, and the time-dependent TGRL composition was observed. Postchallenge, arachidonic acid was 16% [95% CI: 4%, 28%] lower than baseline at 8 h with control. P-OM3 increased TGRL ω-3 fatty acids (EPA 24% [15%, 34%]; DHA 14% [5%, 24%]). The timing of ω-6 oxylipin responses differed by class; arachidonic acid-derived alcohols peaked at 2 h, while linoleic acid-derived alcohols peaked at 4 h (pint = 0.006). P-OM3 increased EPA alcohols by 161% [68%, 305%] and DHA epoxides by 178% [47%, 427%] at 4 h compared to control. In conclusion, this study shows that TGRL fatty acid and oxylipin composition changes following endotoxin challenge. P-OM3 alters the TGRL response to endotoxin challenge by increasing availability of ω-3 oxylipins for resolution of the inflammatory response.

Differential Fatty Acid Accretion in Heart, Liver and Adipose Tissues of Rats Fed Beef Tallow, Fish Oil, Olive Oil and Safflower Oils at Three Levels of Energy Intake

To examine interactive effects of dietary fatty acid composition and energy restriction on tissue fatty acid accretion, mature rats consumed diets containing beef tallow, fish oil, olive oil or safflower oil with free access or at 85% or 68% of free access energy intakes. Restriction was accomplished by adjustment of dietary carbohydrate level. After 10 wk, animals were killed, and the fatty acid compositions of liver, heart and adipose tissues were examined. Compared with animals given free access to diets, body weight gains were reduced at wk 10 in fish oil- and olive oil-fed groups consuming 85% (P < 0.01) and in all groups consuming 68% (P < 0.005) of free access energy intake. Liver and heart weights were also lower (P < 0.05) in all groups restricted to 68% of free access energy intake. The type of dietary fat and the level of energy restriction influenced fatty acid composition in all three tissues at wk 10. In liver tissue, graded energy restriction increased (P < 0.02) proportions of stearic acid and decreased (P < 0.03) those of palmitic acid. In heart tissue, palmitic acid levels decreased (P < 0.01) with energy restriction. In adipose tissue, significant energy restriction-related changes in fatty acid composition varied with type of fat consumed. These results emphasize the importance of whole-body energy balance in addition to dietary fatty acid supply in utilization of dietary fatty acids for tissue deposition vs. oxidation.

Changes in fatty acid composition of mealworm during refrigerated storage

本研究では，市販ミールワーム（Tenebrio molitor）を冷蔵環境下で保存した場合の生存率，体重および脂肪酸組成等の経時的変化について検討した．試験には，市販されているミールワームを用いた．冷蔵日数を0（冷蔵前），10，20，30および45日とし，冷蔵日数ごとに1群あたり200個体のミールワーム群を3群ずつ配置した．測定項目は，保存時の温湿度，各冷蔵日数におけるミールワームの生存率，体重および脂肪酸組成とした．冷蔵日数の経過に伴い生存率および体重の低下がみられた．また，ミールワームの冷蔵日数の経過に伴い総不飽和脂肪酸および多価不飽和脂肪酸の割合が増加することが示唆された．これらのことから，ミールワームを冷蔵保存し生餌として給与する場合，冷蔵日数の経過に伴い生存率，体重および脂肪酸組成が変化することを考慮する必要があると考えられた．

The changes in fatty acid profile during senescence and methyl jasmonate-induced senescence of Ginkgo biloba leaves

The present study describes changes in fatty acid (FA) composition in Ginkgo biloba leaves subjected to senescence and to senescence induced by methyl jasmonate (MeJA). Green leaves were treated with MeJA in lanoline on the abaxial or adaxial side of the leaf blades. After three weeks of treatment, leaf blades and petioles were collected separately for FA analyses. Additionally, petioles and leaf blades were sampled for analyses before the experiment and after 6 weeks when leaf senescence was occurring. Linolenic (C18:3) and palmitic (C16:0) acids appeared to be the quantitatively most abundant FA in leaf blades and petioles of G. biloba. Both leaf senescence and that induced by MeJA caused a decrease in unsaturated FA content, especially linolenic (C18:3). However, the decrease in C18:3 acid in both leaf blades and petioles was greater when MeJA was applied to the abaxial side than when it was applied to the adaxial side of leaves or during senescence. At the same time, saturated FA content increased, resulting in a significant decrease in the ratio of total unsaturated to saturated FA. Since leaf fatty acids occur mainly as components of cell membranes, changes in their composition may have a crucial effect on membrane function and stability, as pointed out in the discussion of the results.

Heat treatment effect on tocopherols, total phenolics and fatty acids in table olives (Olea europaea L.)

The olive fruits are rich source of oil, vitamins, minerals, organic acids and pigments. The fruits contain high level of bioactive compounds. The aim of this study was to examine the effect of heat treatment on tocopherols, total phenolics and antioxidant activity in green and black olives, as well as their fatty acid composition. The instrumental methods used in this experiment were high performance liquid chromatography (HPLC), gas chromatography with flame ionization detection (GC/FID) and spectrophotometric methods. The results revealed that the β+γ-tocopherols content after the heat treatment had the biggest reduction, which was 68.4% for green and 80.2% for black olives. Also, a significant loss of total phenolic content was observed after heat treatment in green and black olives by 18.6% and 18.4%, respectively, as well as antioxidant activity (decrease up to 28.1%). The most abundant fatty acids in green and black olives were oleic (C18:1), palmitic (C16:0) and linoleic acid (C18:2). The changes in fatty acids composition during the heat treatment occurred mostly at the level of polyunsaturated fatty acids, especially linolenic acid (C18:3) in black olives had the significant reduction (by 57.4%) in relation to the initial quantity.

Effect of Gamma Irradiation on Fat Content, Fatty Acids, Antioxidants and Oxidative Stability of Almonds, and Electron Paramagnetic Resonance (EPR) Study of Treated Nuts.

Gamma irradiation has been applied as an efficient and inexpensive method for the sterilization of nuts for years. However, along with the benefits of such treatment, negative effects are possible because of the formation of reactive oxygen species with a toxic effect on important biologically active substances. Because of the scarce and contradictory information in the literature about gamma-irradiated almonds, the aim of our work was the examination of the lipid changes, antioxidant activity, and oxidative stability of almonds treated by 10 and 25 kGy gamma rays, as well as changes in intensity of the EPR spectra as an indicator for the stability of radiation-induced free radicals. The results revealed no significant differences in the EPR spectra of almonds treated at 10 and 25 kGy doses, neither in their intensity nor in kinetic behaviour. The EPR signals decayed exponentially over 250 days, with a decreasing of central line by 90%, with satellite lines by about 73%. No significant changes in the fat content, fatty acids composition, and acid value of irradiated almonds were observed. However, the amount of (alpha)tocopherols decreased from 292 to 175 mg/kg, whereas the conjugated dienes and trienes increased, K232 from 1.3 to 3 and K268 from 0.04 to 0.15, respectively, with the increasing of irradiation dose. The same was observed for total polyphenols in defatted almonds (1374 to 1520 mg/100 g), where in vitro antioxidant activity determined by ORAC and HORAC methods increased from 100 to 156 µmol TE/g and from 61 to 86 µmol GAE/g, respectively. The oxidative stability of oil decreased from 6 to 4 h at 120 °C and from 24.6 to 18.6 h at 100 °C (measured by Rancimat equipment). The kinetic parameters characterizing the oxidative stability of oil from 10 kGy irradiated almonds were studied before and after addition of different concentrations of ascorbyl palmitate as a synergist of tocopherols. Its effectiveness was concentration-dependent, and 0.75 mM ensured the same induction period as that of non-irradiated nut oil. Further enrichment with alpha-tocopherol in equimolar ratio with palmitate did not improve the oil stability. In conclusion, gamma irradiation is an appropriate method for the treatment of almonds without significant changes in fat content and fatty acids composition. The decreasing of oxidative stability after higher irradiation could be prevented by the addition of ascorbyl palmitate.

Changes in milk fat globule physical properties and milk fatty acid composition throughout the lactation cycle of Laoshan goat.

The objective of this study was to investigate the effect of lactation stage on the physical properties of milk fat globules (MFGs) and profiles of milk fatty acids (FAs) of milk from Laoshan dairy goats. Goat colostrum and milk samples were collected on days 1, 3, 30, 90, 150, and 240 postpartum. Milk fat content was found to significantly decrease during the first 90 d of lactation and increase thereafter as lactation progressed (P < 0.01). Average area particle size and volume particle size of MFGs showed trends similar to those of the milk fat content of goat milk with the extension of lactation, and the lowest levels were 2.39 μm and 3.97 μm on day 90, respectively (P < 0.01). The zeta-potential of MFGs significantly increased before 30 d of lactation, with a slight drop on day 90. It increased thereafter and tended to stabilize in the late stages of lactation (P < 0.01). The content of several saturated fatty acids (SFAs) (C10:0-C16:0) in early lactation, especially in colostrum, was lower than that in other stages of lactation (P < 0.05). Branched-chain fatty acids of the iso and anteiso series, including C13:0 anteiso, C15:0 anteiso, and C15:0 iso, were observed at high contents in mid-lactation goat milk (P < 0.01). As lactation progressed (3 d to 240 d), the content of SFAs significantly increased (P < 0.01), while the content of monounsaturated fatty acids and polyunsaturated fatty acids significantly decreased (P < 0.05). Furthermore, the content of C18:0 significantly increased during the first 30 d of lactation and decreased thereafter as lactation progressed (P < 0.01). Our results indicated that lactation stage has a pronounced effect on the physical properties of MFGs and the FA profiles of goat milk.

Fatty acid composition and metabolic partitioning of α-linolenic acid are contingent on life stage in human CD3+ T lymphocytes.

Immune function changes across the life course; the fetal immune system is characterised by tolerance while that of seniors is less able to respond effectively to antigens and is more pro-inflammatory than in younger adults. Lipids are involved centrally in immune function but there is limited information about how T cell lipid metabolism changes during the life course. We investigated whether life stage alters fatty acid composition, lipid droplet content and α-linolenic acid (18:3ω-3) metabolism in human fetal CD3+ T lymphocytes and in CD3+ T lymphocytes from adults (median 41 years) and seniors (median 70 years). Quiescent fetal T cells had higher saturated (SFA), monounsaturated fatty acid (MUFA), and ω-6 polyunsaturated fatty acid (PUFA) contents than adults or seniors. Activation-induced changes in fatty acid composition differed between life stages. The principal metabolic fates of [13C]18:3ω-3 were constitutive hydroxyoctadecatrienoic acid synthesis and β-oxidation and carbon recycling into SFA and MUFA. These processes declined progressively across the life course. Longer chain ω-3 PUFA synthesis was a relatively minor metabolic fate of 18:3ω-3 at all life stages. Fetal and adult T lymphocytes had similar lipid droplet contents, which were lower than in T cells from seniors. Variation in the lipid droplet content of adult T cells accounted for 62% of the variation in mitogen-induced CD69 expression, but there was no significant relationship in fetal cells or lymphocytes from seniors. Together these findings show that fatty acid metabolism in human T lymphocytes changes across the life course in a manner that may facilitate the adaptation of immune function to different life stages.

Chokeberry juice affects membrane lipid status and cellular antioxidant enzymes in healthy women with aerobic training activity

The present study examined the effects of aerobic training alone or combined with chokeberry juice on membrane lipid status and activities of antioxidant enzymes in non-athlete women. Participants were randomly assigned into the training group performing aerobic training three times per week; the chokeberry-training group followed the same training regime and additionally consumed 100 ml of chokeberry juice per day and the control group neither trained nor consumed the juice. Blood samples were collected at baseline and the end of the eight-week-long intervention. Membrane fatty acids’ composition was analyzed by gas-liquid chromatography, while the activities of antioxidant enzymes were measured by spectrophotometry. As a result, the n-3 fatty acids’ content was significantly higher in the chokeberry-training (median (interquartile range) of 5.96 (1.65) %) compared with the control group (5.12 (0.87) %), while saturated fatty acids’ content was lower in the chokeberry-training (40.14±1.19 %) than in the training group (42.59±2.29 %). We detected significantly higher activity of superoxide dismutase in the training (2224 (2170) U/gHb) compared with the chokeberry-training (1252 (734) U/gHb) and control group (1397 (475) U/gHb). Our study indicates that supplementation with chokeberry juice may induce favorable changes in cell fatty acid composition and antioxidant response in women performing aerobic training.

Chokeberry juice affects membrane lipid status and cellular antioxidant enzymes in healthy women with aerobic training activity

The present study examined the effects of aerobic training alone or combined with chokeberry juice on membrane lipid status and activities of antioxidant enzymes in non-athlete women. Participants were randomly assigned into the training group performing aerobic training three times per week; the chokeberry-training group followed the same training regime and additionally consumed 100 ml of chokeberry juice per day and the control group neither trained nor consumed the juice. Blood samples were collected at baseline and the end of the eight-week-long intervention. Membrane fatty acids’ composition was analyzed by gas-liquid chromatography, while the activities of antioxidant enzymes were measured by spectrophotometry. As a result, the n-3 fatty acids’ content was significantly higher in the chokeberry-training (median (interquartile range) of 5.96 (1.65) %) compared with the control group (5.12 (0.87) %), while saturated fatty acids’ content was lower in the chokeberry-training (40.14±1.19 %) than in the training group (42.59±2.29 %). We detected significantly higher activity of superoxide dismutase in the training (2224 (2170) U/gHb) compared with the chokeberry-training (1252 (734) U/gHb) and control group (1397 (475) U/gHb). Our study indicates that supplementation with chokeberry juice may induce favorable changes in cell fatty acid composition and antioxidant response in women performing aerobic training.

Lipid metabolism, fatty acid composition and meat quality in broilers supplemented with increasing levels of defrosted black soldier fly larvae

A feeding experiment was conducted to investigate the impact of feeding defrosted whole black soldier fly larvae (BSFL) to broilers in increasing levels in the ration on blood metabolites, carcass characteristics (CC) and on changes in fatty acid (FA) composition in plasma, muscle and abdominal fat. Day-old chicks (Ross-308; n=252) were assigned to one of four groups each with 6 replicate pens (10-11 birds/pen). The birds were fed either a demand-oriented age-specific control (CON) diet and had no access to BSFL, or fed CON plus BSFL at 10% (L10), 20% (L20) or 30% (L30) of CON feed intake. At weeks (wk) 4 and 6, birds (2 per pen) were slaughtered to collect blood, breast muscle, and abdominal fat samples and to determine CC. Plasma triglyceride concentrations increased in a dose dependent manner with increasing levels of whole BSFL compared with CON (P&lt;0.05). The L30 and L20 had higher plasma non-esterified FA concentrations than CON (P&lt;0.05). There were no differences in slaughter weight and CC between groups (P&gt;0.05). Broilers fed 30% BSFL had the highest saturated FA proportion in plasma, muscle and abdominal fat and the lowest monounsaturated FA proportion in abdominal fat tissue (P&lt;0.05). The levels of total polyunsaturated FA in plasma and abdominal fat were lower in L30 than in CON (P&lt;0.05). In plasma, muscle and abdominal fat, the proportion of conjugated linoleic acid (isomer C18:2cis-9, trans-11) was highest in L30 followed by L20 and L10 compared with CON (P&lt;0.05). Overall, whole BSFL could be included in broiler diets up to 20% to promote sustainability in broiler farming without adverse effects on slaughter weight, meat quality and FA compositions, whereas, the highest inclusion level (i.e. 30%) of whole BSFL in the daily ration was associated with altered FA composition in plasma, fat and meat.

Fatty acid composition on diet and carcasses, growth, body indices and profile serum of Asian redtail catfish (Hemibagrus nemurus) fed a diet containing different levels of EPA and DHA

Background: The Asian redtail catfish Hemibagrus nemurus is a promising commercial aquaculture freshwater big-sized Bagridae catfish across Asian countries such as the Mekong, Malay Peninsula, and Indonesia. This study analysed the effect of eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) supplementation in diets on changes in fatty acid compositions in feed and fish meat, lipid quality (atherogenic index and thrombogenic index), growth rate, body indicators, and serum metabolites of Hemibagrus nemurus juveniles. Methods: A total of 180 Asian redtail catfish (initial weight 54.80 ± 2.72 g) were fed four levels (0, 3,150, 6,300, and 9,450 mg of EPA+DHA/kg feed) sourced from fish oil. Diets were fed in triplicate in freshwater tarpaulin ponds, with 15 fish per tarpaulin pond. During the experiment, fish were fed 3% per day of the biomass weight. Results: Categorically, there were significant differences in the composition of fatty acids in the feed and fish meat. The atherogenic index was between 1.76 and 1.84, and the thrombogenic index was between 0.81 and 0.89 in all fish meat. Growth performance was significantly different between diets, while body indices did not make a significant difference between diets. The fish meat EPA and DHA showed positive linear relationships with diet EPA (p &lt;0.001, r2 = 90%) and DHA diet (p&lt;0.001, r2 = 85%). Serum metabolites among treatments D2 and D3 diet-fed feed for 60 days did not significantly differ. Glucose (GLU) levels had moderate relationships with triglycerides (TAG) (r2 = 65%), and GLU levels strongly correlated with low-density lipoprotein cholesterol (LDL-C) (r2 = 81%). Conclusions: Based on diets and whole-body carcass compositions, growth performance, and serum metabolites, Asian redtail catfish fed a diet containing 6,300 mg of EPA+DHA/kg feed are best for food safety.

Polystyrene microplastics exposure modulated the content and the profile of fatty acids in the Cladoceran Daphnia magna

A growing number of studies has shown that the exposure to microplastics (MPs) of different polymeric compositions can induce diverse adverse effects towards several aquatic species. The vast majority of such studies has been focused on the effects induced by the administration of MPs made by polystyrene (PS; hereafter PS-MPs). However, despite the increase in the knowledge on the potential toxicity of PS-MPs, there is a dearth of information concerning their role in affecting energy resources and/or their allocation. The present study aimed at exploring the impact of 21-days exposure to three concentrations (0.125, 1.25 and 12.5 μg mL−1) of PS-MPs of different sizes (1 and 10 μm) on fatty acids (FAs) profile of the freshwater Cladoceran Daphnia magna. The exposure to the highest tested concentration of PS-MPs induced an overall decrease in D. magna total FAs content, independently of the particle size. Moreover, a change in the accumulation of essential FAs by the diet was noted, with an enhanced synthesis of monounsaturated FAs-rich storage lipids. However, a sort of adaptation to counteract the adverse effects and to re-establish the FAs homeostasis was observed in individuals treated with high PS-MPs concentration, independently of their size. These results indicate that the exposure to PS-MPs could alter the allocation or induce changes in FAs composition in D. magna, with potential long-term consequences on life-history traits of this zooplanktonic species.

Effect of drying processes on the occurrence of lipid oxidation-derived 4-hydroxy-2-hexenal and 4-hydroxy-2-nonenal in Spanish mackerel (Scomberomorus niphonius).

In this study, dry-cured Spanish mackerel (Scomberomorus niphonius, DCSM) was prepared via three different methods (hot-air drying, cold-air drying, and sun drying). The content of 4-hydroxy-2-hexenal (HHE) and 4-hydroxy-2-nonenal (HNE) derived from lipid oxidation in whole processes was investigated by HPLC-MS/MS. The changes in fatty acid composition were detected by GC-MS, and the degree of lipid oxidation was evaluated by the levels of acid values (AV), peroxide values (POV), and thiobarbituric acid-reactive substances (TBARS). The results showed that the drying process significantly accelerated lipid oxidation in DCSM. The contents of HHE and HNE were significantly increased after processing. The content of HHE was higher by 18.44-, 13.45-, and 16.32-folds compared with that of HNE after three different processes, respectively. The HHE and HNE contents fluctuated upward during the hot-air and cold-air drying process. However, the contents of HHE and HNE increased time-dependent during the sun drying process, with the highest values of 86.33 ± 10.54 and 5.29 ± 0.54 mg/kg fish among the three different processes. Besides, there was a significant positive correlation between HHE contents and n-3 fatty acids content in hot-air drying and sun drying processes (Pearson's r=.991/.996), and HNE occurrence was closely related to n-6 fatty acid content in sun drying process (Pearson's r=.989). Regression analysis indicated that the content of HHE and TOTOXTBA values in DCSM showed good linear relationships (R 2 value=.907), which suggested that the content of HHE could be used to estimate the oxidative deterioration of dry-cured fish products.

Elongation of Long-Chain Fatty Acids Is Crucial for Hematopoietic Stem Cell Engraftment and Leukemia Propagation

Lipid metabolism plays a crucial role in regulating physiological stem cells and cancer cells. Variations in length or degree of desaturation of fatty acid (FA) chains greatly contribute to lipid diversity, but whether it significantly regulates hematopoietic cell biology remains unknown. The enzyme ELOVL6 converts C16 saturated and monounsaturated FAs to C18 species. Elovl6 gene disruption (Elo6KO) in mice decreases the proportions of stearate (C18:0) and oleate (C18:1n-9) and increases those of palmitate (C16:0) and palmitoleate (C16:1n-7). Here, we report that ELOVL6 is essential for hematopoietic stem cells (HSC) engraftment after bone marrow (BM) transplantation and acute myeloid leukemia (AML) development in a mouse model. To determine whether hematopoietic cells of Elo6KO mice exhibit changes in FAs composition, we analyzed FAs in BM cell lysates. We found that the ratio of stearate to palmitate (C18:0/C16:0 ratio) was significantly decreased in Elo6KO cells compared to WT cells. To assess the effects of Elovl6 loss on the mouse HSC, we performed competitive repopulation assays. Using control or Elo6KO donor BM cells mixed in a 1:1 ratio with competitor BM cells, the chimerism of peripheral blood (PB) was about 50% in mice transplanted with control cells but remained at < 0.2% in those with Elo6KO cells at 12 weeks after transplantation. Even when transplanted Elo6KO donor cells with the competitor in a 10:1 ratio, the chimerism of PB was similarly low. Next, we investigated the roles of Elovl6 in leukemogenesis. We infected lineage-negative and c-Kit+ cells from WT or Elo6KO BM with MLL-AF9(MA9) retrovirus and transplanted lethally irradiated mice with either WT or Elo6KO MA9 cells. All mice receiving WT MA9 cells developed AML; however, AML propagation in Elo6KO MA9 cell-transplanted recipients was blocked. Elo6KO MA9 cell-transplanted mice survived until 6 months after transplantation. To assess the mechanisms underlying these phenotypes, we performed RNA-seq and gene enrichment analysis (GSEA) using CD34-, lineage-negative, Sca-1+ and c-Kit+ (CD34-LSK) cells and MA9 cells from Elo6KO or control mice. Chemotaxis, CXCR4 pathways, and their related target gene sets were enriched in Elo6KO cells, relative to control in both CD34-LSK cells and MA9 cells. We tested the chemotaxis of Elo6KO CD34-LSK and MA9 cells toward CXCL12 in a migration assay. A greater fraction of WT CD34-LSK and MA9 cells than that of these Elo6KO cells migrated to the CXCL12-containing chamber. We then examined the pharmacologic effects of inhibiting the PI3K pathway on chemotaxis. In a migration assay, the presence of PI3K inhibitor, Copanlisib, decreased the migration rate in WT MA9 cells, but not significantly in Elo6KO MA9 cells, which was already compromised. By contrast, AKT inhibitor, MK2206, did not alter WT or Elo6KO MA9 cell migration. In GSEA, Rac1-related pathways were enriched in Elo6KO cells. We thus investigated whether Rac1 activation was blocked by Elovl6 loss. The levels of the GTP-bound Rac1 were markedly increased in WT MA9 cells following CXCL12 stimulation compared to control, while those were not significantly different with/wo CXCL12 stimulation in Elo6KO MA9 cells. Given impaired chemotaxis and CXCR4-PI3K-Rac1 signaling in Elo6KO cells, we then investigated whether these cells exhibited altered actin remodeling in response to CXCL12. As expected, CXCL12 treatment induced lamellipodia formation in WT CD34-LSK cells, but not in Elo6KO CD34-LSK cells. Thus, ELOVL6 may regulate a CXCL12-CXCR4 pathway, resulting in PI3K-Rac1-mediated cytoskeletal remodeling and chemotaxis. Finally, to determine whether exogenously expressed Elovl6 could rescue Elo6KO MA9 cell phenotypes, we generated Elo6KO MA9 cells expressing Flag-tagged ELOVL6 (Elo6KO MA9Elo6) and mock controls (Elo6KO MA9mock). To evaluate the rescue of AML propagation, we transplanted lethally irradiated syngeneic mice with either Elo6KO MA9mock or Elo6KO MA9Elo6 cells. Among Elo6KO MA9mock transplanted mice, few recipients developed AML, while 10 out of 14 recipients had died due to AML after Elo6KO MA9Elo6 cell transplant. In summary, this study demonstrates novel and unexpected outcomes in normal HSCs and AML driver-transformed cells following lipid changes induced by Elovl6 deficiency. Altering lipid diversity could be a potential strategy to treat AML.

Extracellular stimulation of lung fibroblasts with arachidonic acid increases interleukin 11 expression through p38 and ERK signaling.

Interleukin-11 (IL-11) is a pleiotropic cytokine that regulates proliferation and motility of cancer cells. Fibroblasts reside in the cancer microenvironment and are the primary source of IL-11. Activated fibroblasts, including cancer-associated fibroblasts that produce IL-11, contribute to the development and progression ofcancer, and inducefibrosis associated with cancer. Changes in fatty acid composition or its metabolites, and an increase in free fatty acids have been observed in cancer. The effect of deregulated fatty acids on the development and progression of cancer isnot fully understood yet. In the present study, we investigated the effects of fatty acids on mRNA expression and secretion of IL-11 in lung fibroblasts. Among the eight fatty acids added exogenously, arachidonic acid (AA) increased mRNA expression and secretion of IL-11 in lung fibroblasts in a dose-dependent manner. AA-induced upregulation of IL-11 was dependent on the activation of the p38or ERK MAPK signaling pathways. Furthermore, prostaglandin E2, associated with elevated cyclooxygenase-2 expression, participated in the upregulation of IL-11 via its specific receptor in an autocrine/paracrine manner. These results suggest that AA may mediate IL-11 upregulation in lung fibroblasts in thecancer microenvironment, accompanied by unbalanced fatty acid composition.

Effects of gradually increasing drying temperatures on energy aspects, fatty acids, chemical composition, and in vitro ruminal fermentation of acorn.

Acorns are commonly used to meet energy, protein, and mineral needs of livestock in various parts of the world. However, since acorns have quite a high moisture content at harvest, they should be stored as dried to prevent loss of nutrients and spoilage throughout storage periods. The aim of this study is to determine the drying kinetics, color, energy aspects, crude protein, crude ash, crude oil, fatty acid composition, ADF, NDF, condensed tannin, and mineral composition properties of acorns dried at gradually increasing drying temperatures. Drying processes were carried out in an air-convective dryer at temperatures of 40, 60, 80, 100, and 120 °C. The Logistic model was identified as the best model for describing current drying conditions. Increasing drying temperatures reduced L* (lightness) values and increased thermal efficiency and effective moisture diffusion values. In terms of energy efficiency, the best outcomes were achieved at 80 °C and 120 °C drying temperatures. Drying temperatures had highly significant effects on nutritional traits of acorn samples. Increasing drying temperatures increased fiber content, gas-methane production, and energy values and reduced crude protein and oil contents. Some minerals decreased and some others increased with increasing drying temperatures. Increasing drying temperatures caused slight changes in fatty acid compositions. In terms of animal drying and feeding characteristics, it was determined that a drying temperature of 80 °C was ideal for acorn drying.