Lipid mediators in platelet concentrate and extracellular vesicles: Molecular mechanisms from membrane glycerophospholipids to bioactive molecules

Platelets are collected for transfusion to patients with different hematological disorders, and for logistical reasons, platelets are stored as concentrates. Despite the carefully controlled conditions, platelets become activated during storage, and platelet concentrates (PLCs) may cause adverse inflammatory reactions in the recipients. We studied by mass spectrometry the lipidomic changes during storage of the clinical PLCs, the platelets isolated from PLCs, and the extracellular vesicles (EVs) thereof. The release of EVs from platelets increased with the prolonged storage time. The molar percentages of arachidonic acid -containing species were increased during storage especially in the phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine classes of glycerophopholipids. The increase of these species in the membrane glycerophopholipid composition paralleled the production of both proinflammatory and proresolving lipid mediators (LMs) as the amount of the arachidonic acid-derived LMs such as thromboxane B2 and prostaglandin E2 also increased in time. Moreover, several monohydroxy pathway markers and functionally relevant proinflammatory and proresolving LMs were detected in the PLC and the EVs, and some of these clearly accumulated during storage. By Western blot, the key enzymes of these pathways were shown to be present in the platelets and in many cases also in the EVs. Since the EVs were enriched in the fatty acid precursors of LMs, harbored LM-producing enzymes, contained the related monohydroxy pathway markers, and also secreted the final LM products, the PLC-derived EVs appear to have the potential to regulate inflammation and healing, and may thereby aid the platelets in exerting their essential physiological functions.Peer reviewe

LDL aggregation susceptibility is higher in healthy South Asian compared with white Caucasian men

BACKGROUND: South Asians are more prone to develop atherosclerotic cardiovascular disease (ASCVD) compared with white Caucasians, which is not fully explained by classical risk factors. We recently reported that the presence of aggregation-prone low-density lipoprotein (LDL) in the circulation is associated with increased ASCVD mortality. OBJECTIVE: We hypothesized that LDL of South Asians is more prone to aggregate, which may be explained by differences in their LDL lipid composition. METHODS: In this cross-sectional hypothesis-generating study, LDL was isolated from plasma of healthy South Asians (n = 12) and age- and BMI-matched white Caucasians (n = 12), and its aggregation susceptibility and lipid composition were analyzed. RESULTS: LDL from South Asians was markedly more prone to aggregate compared with white Caucasians. Among all measured lipids, sphingomyelin 24:0 and triacylglycerol 56:8 showed the highest positive correlation with LDL aggregation. In addition, LDL from South Asians was enriched in arachidonic acid containing phosphatidylcholine 38:4 and had less phosphatidylcholines and cholesteryl esters containing monounsaturated fatty acids. Interestingly, body fat percentage, which was higher in South Asians (+26%), positively correlated with LDL aggregation and highly positively correlated with triacylglycerol 56:8, sphingomyelin 24:0, and total sphingomyelin. CONCLUSIONS: LDL aggregation susceptibility is higher in healthy young South Asians compared with white Caucasians. This may be partly explained by the higher body fat percentage of South Asians, leading to sphingomyelin enrichment of LDL. We anticipate that the presence of sphingomyelin-rich, aggregation -prone LDL particles in young South Asians may increase LDL accumulation in the arterial wall and thereby contribute to their increased risk of developing ASCVD later in life. (C) 2019 National Lipid Association. Published by Elsevier Inc.Peer reviewe

hiPSC-derived hepatocytes closely mimic the lipid profile of primary hepatocytes: A future personalised cell model for studying the lipid metabolism of the liver

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Hepatic P450 Enzyme Activity, Tissue Morphology and Histology of Mink (Mustela vison) Exposed to Polychlorinated Dibenzofurans

Dose- and time-dependent effects of environmentally relevant concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQ) of 2,3,7,8-tetrachlorodibenzofuran (TCDF), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), or a mixture of these two congeners on hepatic P450 enzyme activity and tissue morphology, including jaw histology, of adult ranch mink were determined under controlled conditions. Adult female ranch mink were fed either TCDF (0.98, 3.8, or 20 ng TEQTCDF/kg bw/day) or PeCDF (0.62, 2.2, or 9.5 ng TEQPeCDF/kg bw/day), or a mixture of TCDF and PeCDF (4.1 ng TEQTCDF/kg bw/day and 2.8 ng TEQPeCDF/kg bw/day, respectively) for 180 days. Doses used in this study were approximately eight times greater than those reported in a parallel field study. Activities of the cytochrome P450 1A enzymes, ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-deethylase (MROD) were significantly greater in livers of mink exposed to TCDF, PeCDF, and a mixture of the two congeners; however, there were no significant histological or morphological effects observed. It was determined that EROD and MROD activity can be used as sensitive biomarkers of exposure to PeCDF and TCDF in adult female mink; however, under the conditions of this study, the response of EROD/MROD induction occurred at doses that were less than those required to cause histological or morphological changes

Diet-Independent Remodeling of Cellular Membranes Precedes Seasonally Changing Body Temperature in a Hibernator

Polyunsaturated fatty acids (PUFA) have a multitude of health effects. Their incorporation into membrane phospholipids (PL) is generally believed to depend directly on dietary influx. PL influence transmembrane protein activity and thus can compensate temperature effects; e.g. PL n-6 PUFA are thought to stabilize heart function at low body temperature (Tb), whereas long chain (>C18) n-3 PUFA may boost oxidative capacity. We found substantial remodeling of membranes in free-living alpine marmots which was largely independent of direct dietary supply. Organ PL n-6 PUFA and n-6 to n-3 ratios were highest at onset and end of hibernation after rapid increases during a brief transitional period prior to hibernation. In contrast, longer chain PL n-3 PUFA content was low at end of summer but maximal at end of hibernation. After termination of hibernation in spring, these changes in PL composition were rapidly reversed. Our results demonstrate selective trafficking of PUFA within the body, probably governed by a circannual endogenous rhythm, as hibernating marmots were in winter burrows isolated for seven months from food and external cues signaling the approaching spring. High concentrations of PL n-6 PUFA throughout hibernation are in line with their hypothesized function of boosting SERCA 2a activity at low Tb. Furthermore, we found increasing rate of rewarming from torpor during winter indicating increasing oxidative capacity that could be explained by the accumulation of long-chain PL n-3 PUFA. It may serve to minimize the time necessary for rewarming despite the increasing temperature range to be covered, because rewarming is a period of highest metabolic rate and hence production of reactive oxygen species. Considering the importance of PUFA for health our results may have important biomedical implications, as seasonal changes of Tb and associated remodeling of membranes are not restricted to hibernators but presumably common among endothermic organisms

Fatty acid signatures as indicators of diet in great skuas <i>stercorarius skua</i>, Shetland

Fatty acid signatures (FAS) were determined in plasma and adipose tissue of great skuas Stercorarius skua from Shetland in order to test the applicability of this biomarker in estimating diets of wild scavenging seabirds. The plasma FAS were compared with those of captive herring gulls Larus argentatus, which were fed typical Northeast Atlantic demersal and pelagic fish. The individual fatty acids that showed the largest proportional changes in FAS due to changes of dietary fish in herring gulls also varied the most in wild great skuas, suggesting a dietary origin of these changes in FAS. Thus, great skuas that had recently been feeding largely on a demersal or terrestrial diet were distinguished from individuals feeding mainly on a pelagic diet. Pronounced variation in the plasma FAS of great skuas suggests either very flexible feeding behaviour or individual dietary specialisation, which concurs with previous studies based on pellets. Individuals that regurgitated pellets consisting only of demersal fish, bird or rabbit showed larger values of a specific polyunsaturated fatty acid ratio (20:4n-6/18:3n-3+18:4n-3+20:5n-3) than birds whose pellets also contained remains of pelagic fish. Although pellet data showed a clear dominance of demersal fish in the summer diet of the great skua, the large proportions of long-chain monounsaturated fatty acids (e.g. 20:1n-9 and 22:1n-11) in adipose tissue of the great skua suggest that a considerable part of fat accumulated outside the breeding season comes from fatty pelagic fis

Fatty acid signatures and stable isotopes as dietary indicators in North Sea seabirds

Fatty acid signatures (FAS) of plasma and stable isotopes of carbon (8 13 C) and nitrogen (delta N-15) of red blood cells were determined in northern gannets Morus bassanus, great skuas Sterco-rarius skua, shags Phalacrocorax aristotelis, and common guillemots Uria aalge from colonies in the North Sea (collected 2002 to 2003) in order to compare foraging ecologies, and especially to assess the extent to which birds feed on demersal or pelagic prey. The biochemical markers in great skua and gannet indicated that these species feed at a relatively high trophic level, and high variance, especially in great skua, demonstrated either a wide range of food types, individual dietary specialisation or both. The biochemical markers suggested that demersal fish are important constituents of great skua and gannet diets, and thus changes in fisheries discard rates probably influence these populations. In contrast, clear pelagic characteristics and low variance in the markers showed that the diet of common guillemots and shags is pelagic and varies little in composition. Comparison with the reference FAS data for North Sea fish confirmed the dependence of common guillemots on few shoaling pelagic species of fish, probably mainly young sandeels Ammodytes marinu

Fatty acid signatures in plasma of captive herring gulls as indicators of demersal or pelagic fish diet

Current fishing practices provide scavenging seabirds with discarded demersal fish. In order to study the impact of fishery management measures and alterations in the availability of discards on seabird populations, accurate information on the birds' diet is essential. Studies of pellets and prey remains provide a biased picture and tend to be limited to seabird breeding seasons. Studying biochemical markers in bird tissues can complement other methods. In this study, captive herring gulls &lt;i&gt;Larus argentatus&lt;/i&gt; were fed alternating diets of North Atlantic demersal and pelagic fish, and changes in the fatty acid signatures (FAS) of the birds' plasma were followed. The large differences in FAS of demersal and pelagic fish caused several clearly detectable differences in the plasma FAS of the gulls fed on these fish. A change from demersal to pelagic fish or vice versa could be detected in plasma FAS within 5 d of switching the diet, and transient changes in the gull's nutritional status did not disturb the use of the FAS. Relatively high levels of branched-chain 17:0, 18:1n-7 and 20:4n-6 are indicative of a diet of demersal fish, and high levels of 14:0, 22:1n-11, 20:1n-9, 18:2n-6, 18:3n-3 and 18:4n-3 occur when gulls eat pelagic fish. These reference FAS can be used to estimate the importance of demersal and pelagic fish in the recent diet of scavenging seabirds

Moisture Behavior of Timber-Framed External Wall Structures in Nordic Climate

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Fatty acid signature analysis confirms foraging resources of a globally endangered Mediterranean seabird species: calibration test and application to the wild

Tissue fatty acid signatures (FAS) can complement traditional methods of studying seabird diets. Although plasma lipid FAS are known to indicate dietary changes qualitatively, here we test whether they can be used to determine the proportions of different dietary items in a quantitative manner.2. Captive herring gulls (Larus argentatus) were fed North Atlantic plaice Pleuronectes platessa (demersal species made available to wild seabirds by fisheries) and herring Clupea harengus (pelagic fish often found naturally in their diet) with different mixing ratios (0%, 10%, 20% and 50% herring).3. Major fatty acids did not indicate diet, but several minor components in plasma, for example, 14 : 0, 18 : 3n-3, 18 : 4n-3 and C20-22 monounsaturated fatty acids (MUFA), showed good correlations with diet composition. Different fatty acids were incorporated from diet into plasma lipids with different calibration coefficients.4. Together with dose-dependent but inefficient (low calibration coefficient) transfer of 22 : 1n-11 (a major fatty acid of herring) to the plasma FAS of the gulls, the percentages of potential chain shortening products of 22 : 1n-11, that is, 20 : 1n-11, 18 : 1n-11 and 16 : 1n-11 increased with increasing proportion of herring in the diet. Notably, the dietary supply of these fatty acids itself did not change. Thus the metabolic products of certain dietary fatty acids can reflect the amount of their dietary precursors in a quantitative way.5. Despite the fact that many major fatty acids in FAS of seabird plasma are greatly modified by endogenous metabolism, several minor components of FAS (in this experiment 14 : 0, branched chain 17 : 0, 18 : 1n-7, 18 : 3n-3, 18 : 4n-3, C20-22 MUFA with their chain shortening products, and 22 : 4n-6) that can be accurately and reliably quantified by gas chromatography, vary proportionally to diet composition, allowing their use for monitoring temporal and spatial differences in seabird diet