Phospholipid Levels Research Articles

Effects of Tamoxifen Administration on Lipid Profile in Female Albino Rats

This study is aimed at investigating the effects of tamoxifen on lipid profile. In order to achieve this, tamoxifen was administered once daily intraperitoneally to the female rats at a dose of 2.07mg/kg body weight for 1 and 2 weeks, while a group of rats was allowed to recover for a week after 2 weeks of tamoxifen administration. Rats in the control group were similarly treated but were given corn oil instead of the drug. Tamoxifen administration caused perturbations of major lipids in the animals. Administration of tamoxifen for 1 week lowered cholesterol and triglycerides levels in the plasma by 23.63 % and 39.74 % respectively and in the low density lipoproteins and very low density lipoproteins (LDL+VLDL) by 79.72 % and 67.59 % respectively, while it increased high density lipoproteins (HDL) cholesterol by 3.44 fold. In the tissues, tamoxifen administration for 2 weeks did not significantly affect cholesterol and triglycerides levels but phospholipid levels in the liver, kidney and heart were lowered by 52.38 %, 42.98 % and 73.82 % respectively, while phospholipidosis was the hallmark of its effect in the spleen. The result of our study affirmed that tamoxifen exerts a favourable effect on lipid profile. The hypocholesterolemic and hypotriglyceridesmia effects of tamoxifen observed in this study may partially explain the decrease in coronary heart disease related mortality seen in patients receiving tamoxifen treatment.

Virgin coconut oil and tuberculosis: A mini-review

Virgin coconut oil is widely promoted and used as healthy and beneficial oil. One of them is caused by antimicrobials. Caprylic, caproic acid, capric acid, lauric acid and tau glyceryl monolaurate are other VCO compositions. Furthermore, due to the non-heating manufacturing process, the content in VCO can reduce cholesterol levels of triglycerides, LDL, phospholipids, VLDL and increase HDL in blood serum. VCO consumption lowers the number of Mycobacterium tuberculosis colonies while increasing the conversion of BTA sputum. Until now, the prevalence of tuberculosis (TB) disease was extremely high. VCO can be used as a supplement to help TB patients recover faster.

Fatty acid oxidation protects cancer cells from apoptosis by increasing mitochondrial membrane lipids.

Overcoming resistance to chemotherapies remains a major unmet need for cancers, such as triple-negative breast cancer (TNBC). Therefore, mechanistic studies to provide insight for drug development are urgently needed to overcome TNBC therapy resistance. Recently, an important role of fatty acid β-oxidation (FAO) in chemoresistance has been shown. But how FAO might mitigate tumor cell apoptosis by chemotherapy is unclear. Here, we show that elevated FAO activates STAT3 by acetylation via elevated acetyl-coenzyme A (CoA). Acetylated STAT3 upregulates expression of long-chain acyl-CoA synthetase 4 (ACSL4), resulting in increased phospholipid synthesis. Elevating phospholipids in mitochondrial membranes leads to heightened mitochondrial integrity, which in turn overcomes chemotherapy-induced tumor cell apoptosis. Conversely, in both cultured tumor cells and xenograft tumors, enhanced cancer cell apoptosis by inhibiting ASCL4 or specifically targeting acetylated-STAT3 is associated with a reduction in phospholipids within mitochondrial membranes. This study demonstrates a critical mechanism underlying tumor cell chemoresistance.

Simulated Night-Shift Schedule Disrupts the Plasma Lipidome and Reveals Early Markers of Cardiovascular Disease Risk.

IntroductionThe circadian system coordinates daily rhythms in lipid metabolism, storage and utilization. Disruptions of internal circadian rhythms due to altered sleep/wake schedules, such as in night-shift work, have been implicated in increased risk of cardiovascular disease and metabolic disorders. To determine the impact of a night-shift schedule on the human blood plasma lipidome, an in-laboratory simulated shift work study was conducted.MethodsFourteen healthy young adults were assigned to 3 days of either a simulated day or night-shift schedule, followed by a 24-h constant routine protocol with fixed environmental conditions, hourly isocaloric snacks, and constant wakefulness to investigate endogenous circadian rhythms. Blood plasma samples collected at 3-h intervals were subjected to untargeted lipidomics analysis.ResultsMore than 400 lipids were identified and quantified across 21 subclasses. Focusing on lipids with low between-subject variation per shift condition, alterations in the circulating plasma lipidome revealed generally increased mean triglyceride levels and decreased mean phospholipid levels after night-shift relative to day-shift. The circadian rhythms of triglycerides containing odd chain fatty acids peaked earlier during constant routine after night-shift. Regardless of shift condition, triglycerides tended to either peak or be depleted at 16:30 h, with chain-specific differences associated with the direction of change.DiscussionThe simulated night-shift schedule was associated with altered temporal patterns in the lipidome. This may be premorbid to the elevated cardiovascular risk that has been found epidemiologically in night-shift workers.

Research Note: Comparison of the texture, structure, and composition of eggs from local Chinese chickens and a highly selected line of egg-type chickens and analysis of the effects of lipids on texture

Egg yolk texture affects consumer egg preference. The sensory characteristics of eggs are affected by not only the cooking method but also the maternal breed. In this study, we investigated the texture, structure, and nutritional differences between the cooked yolks of eggs obtained from Hetian Dahei (HTDH) and Rhode Island Red (RIR) chickens. The springiness, cohesiveness, gumminess, chewiness, and resilience of HTDH egg yolks were lower, and the hardness was higher than those of RIR egg yolks. Moreover, scanning electron microscopy revealed that HTDH egg yolk particles were smaller and that HTDH egg yolks had a denser protein network than those of RIR egg yolks. Lipid and protein levels were higher, whereas water contents were lower in uncooked HTDH egg yolks than in uncooked RIR egg yolks. Liquid chromatography tandem mass spectrometry further revealed that lower cohesiveness was associated with higher levels and greater variety of lipids in egg yolks. Moreover, increased phospholipid levels reduced egg yolk cohesiveness. Thus, the eggs of local Chinese chicken breeds were superior to those of a highly selected broiler chicken breed in terms of texture, structure, and nutritional composition, which may influence egg variety selection.

Raman Microspectroscopy Identifies Biochemical Activation Fingerprints in THP-1- and PBMC-Derived Macrophages.

(1) The monocytic leukemia cell line THP-1 and primary monocyte-derived macrophages (MDMs) are popular in vitro model systems to study human innate immunity, wound healing, and tissue regeneration. However, both cell types differ significantly in their origin and response to activation stimuli. (2) Resting THP-1 and MDMs were stimulated with lipopolysaccharide (LPS) and interferon γ (IFNγ) and analyzed by Raman microspectroscopy (RM) before and 48 h after activation. Raman data were subsequently analyzed using principal component analysis. (3) We were able to resolve and analyze the spatial distribution and molecular composition of proteins, nucleic acids, and lipids in resting and activated THP-1 and MDMs. Our findings reveal that proinflammatory activation-induced significant spectral alterations at protein and phospholipid levels in THP-1. In MDMs, we identified that nucleic acid and non-membrane-associated intracellular lipid composition were also affected. (4) Our results show that it is crucial to carefully choose the right cell type for an in vitro model as the nature of the cells itself may impact immune cell polarization or activation results. Moreover, we demonstrated that RM is a sensitive tool for investigating cell-specific responses to activation stimuli and monitoring molecular changes in subcellular structures.

Integrated Metabolomics and Network Pharmacology Analysis Immunomodulatory Mechanisms of Qifenggubiao Granules.

Background: Qifenggubiao granules (QFGBG) is a new Chinese medicine independently developed by Heilongjiang Academy of Traditional Chinese Medicine, which combines the essence of Yupingfeng powder and Shengmai yin (invention patent number: CN1325098C, approval number: Sinopharm Zhunzi B20020410), and has been included in the 2020 edition of Chinese Pharmacopoeia. It has remarkable pharmacodynamic results and conclusive clinical effects in the treatment of allergic rhinitis, chronic cough and other diseases. Previous pharmacological studies have shown that it has immunomodulatory effect, but its immunomodulatory mechanism is still unclear. Methods: In this study, cyclophosphamide (CTX) was used to establish the immune hypofunction model in mice, and the weight change, index of immune organs in spleen and thymus, pathological sections of immune organs and inflammatory factors were used to evaluate the model. Based on the metabolic biomarkers obtained by metabonomics technology, the potential targets of Qifeng Gubiao Granule immunomodulation were obtained by integrating the targets of blood components, metabolites and diseases through network pharmacology. Meanwhile, GO enrichment analysis and KEGG pathway analysis were carried out on the potential targets. Results: QFGBG can increase body weight and organ index, and recover immune organ damage caused by CP. Metabonomics identified 13 metabolites with significant changes, among which the level of phospholipid (PC) metabolites decreased significantly in the model group. Sphingosine -1- phosphate, 1- palmitoyl phosphatidylcholine [LysoPC (16:0/0:0)] and other metabolites were significantly increased in the model group, and 98 targets of Qifeng’s external immune regulation were obtained by intersecting 629 component targets, 202 metabolite targets and 1916 disease targets. KEGG pathway analysis obtained 233 related metabolic pathways, and the top 20 metabolic pathways mainly involved IL-17 signaling pathway, TNF signaling pathway, Sphingolipid signaling pathway, and so on. Conclusion: QFGBG may act on AKT1, IL6, MAPK3, PTGS2, CASP3, MAPK1, ESR1, PPARG, HSP90AA1, PPARA and other targets, acting through Sphingolipid signaling pathway and signaling pathway. Combined with pharmacodynamic evaluation, the immunomodulatory effect of QFGBG was confirmed, and the immunomodulatory mechanism of QFGBG with multiple targets and multiple pathways was preliminarily clarified.

Lipid composition of oocytes and tissues of sturgeons depending on conditions of detention

Shortage of sturgeon spawners has led to the need for reservation and long-term detention of spawners, creation of their own brood stocks. The issues of assessing the functional state of producers and the reproductive products and offspring become topical. The wintering conditions of fish in cages at the natural course of temperatures negatively affect their physiological state. During this period, the fish actively move in the cages, but do not feed. The detention of sturgeon spawners in the pools with regulating the parameters of the aquatic environment makes it possible to stabilize the cycle of maturation of the gonads and increase the number of fish-producing females. The lipid composition of caviar affects its fish-breeding quality. The main components of sturgeon caviar fats are triglycerides and lipoid substances, which are represented by phospholipids that are actively involved in generative metabolism during the maturation of gonads. The main fraction of oocyte lipids is represented by triglycerides, whose level in the oocytes of fish from recirculating water installation (RWI) is higher in comparison with cage fish. It was found that sterlet oocyte lipids are mainly represented by triglycerides. Their concentration in the oocytes of fish kept in RWI is higher in comparison with fish kept in cages. Against the higher amount of triglycerides in fish roe from RWI, a decrease in the level of phospholipids and cholesterol was noted. The aging conditions of producers affect the composition of the main lipid fractions. As a result of the research, a relationship was established between the content of polyunsaturated fatty acids in the tissues of aquatic organ-isms and environmental conditions. The amount of saturated and monounsaturated fatty acids in the muscles of fish kept in RWI was higher than in the tissues of fish kept in cages. Increasing proportion of polyunsaturated fatty acids in the eggs of fish kept in cages indicates a fairly high utilization of monounsaturated fatty acids.

The Effects of Exercise on Plaque Volume and Composition in a Mouse Model of Early and Late Life Atherosclerosis.

BackgroundExercise is associated with a less atherogenic lipid profile; however, there is limited research on the effect of exercise on atherosclerotic plaque composition and markers of plaque stability.MethodsA total of 110 apolipoprotein (apo)E−/− mice were placed on a chow diet and randomly assigned to control or exercise for a period of 10 weeks, commencing either at 12 weeks of age (the early-stage atherosclerosis, EA group) or at 40 weeks of age (the late-stage atherosclerosis, LA group). At the end of the exercise period, blood was assayed for lipids. Histologic analysis of the aortic sinus was undertaken to assess plaque size and composition that includes macrophage content, monocyte chemoattractant protein (MCP)-1, matrix metalloproteinase-2 (MMP-2), and tissue inhibitors of metalloproteinase 1 and 2 (TIMP-1 and 2).ResultsA total of 103 mice (38 EA, 65 LA) completed the protocol. In the EA group, exercise reduced plasma total cholesterol (TC) (−16%), free cholesterol (−13%), triglyceride (TG) (−35%), and phospholipid (−27%) levels, when compared to sedentary control mice (p < 0.01). In the EA group, exercise also significantly reduced plaque stenosis (−25%, p < 0.01), and there were higher levels of elastin (3-fold increase, p < 0.0001) and collagen (11-fold increase, p < 0.0001) in plaques, compared to control mice. There was an increase in plaque MMP-2 content in the exercise group (13% increase, p < 0.05) but no significant difference in macrophage or MCP-1 content. In the LA group, exercise reduced plaque stenosis (−18%, p < 0.05), but there was no significant difference in plaque composition. There was no difference in macrophage, MCP-1, or MMP-2 content in the LA groups. TIMP-1 was lower with exercise in both the EA and LA groups (−59%, p < 0.01 and −51%, p < 0.01 respectively); however, there was no difference in TIMP-2 levels.ConclusionA 10-week exercise period reduces atherosclerotic plaque stenosis when commenced at both early- and late-stage atherosclerosis. Intervening earlier with exercise had a greater beneficial effect on lipids and plaque composition than when starting exercise at a later disease stage.

Changes in the Cerebrospinal Fluid and Plasma Lipidome in Patients with Rett Syndrome

Rett syndrome (RTT) is defined as a rare disease caused by mutations of the methyl-CpG binding protein 2 (MECP2). It is one of the most common causes of genetic mental retardation in girls, characterized by normal early psychomotor development, followed by severe neurologic regression. Hitherto, RTT lacks a specific biomarker, but altered lipid homeostasis has been found in RTT model mice as well as in RTT patients. We performed LC-MS/MS lipidomics analysis to investigate the cerebrospinal fluid (CSF) and plasma composition of patients with RTT for biochemical variations compared to healthy controls. In all seven RTT patients, we found decreased CSF cholesterol levels compared to age-matched controls (n = 13), whereas plasma cholesterol levels were within the normal range in all 13 RTT patients compared to 18 controls. Levels of phospholipid (PL) and sphingomyelin (SM) species were decreased in CSF of RTT patients, whereas the lipidomics profile of plasma samples was unaltered in RTT patients compared to healthy controls. This study shows that the CSF lipidomics profile is altered in RTT, which is the basis for future (functional) studies to validate selected lipid species as CSF biomarkers for RTT.

A new strategy in rearing of European flounder: using live Enchytraeus albidus to enhance juvenile growth

This study reports the use of the annelid worm Enchytraeus albidus as a live feed for reared juvenile European flounder, Platichthys flesus. We investigated growth, lipid composition and mortality in small scale (hundreds of fish) and large scale (thousands of fish) rearing. Live Enchytraeus had a relatively low content of the essential omega-3 fatty acid, docosahexaenoic acid (DHA), but similar levels of other essential fatty acids and amino acids as the normally used commercial dry feed. Despite low DHA levels in live worms, juvenile flounder fed Enchytraeus grew twice as fast as fish fed commercial dry feed. DHA levels in membrane phospholipids of juvenile flounder became depleted when fed Enchytraeus, but this had no apparent negative consequences for development or health of the fish. Our study suggests that the use of Enchytraeus as a live feed for European flounder is feasible at a large scale.

Inositol depletion regulates phospholipid metabolism and activates stress signaling in HEK293T cells

Inositol plays a significant role in cellular function and signaling. Studies in yeast have demonstrated an “inositol-less death” phenotype, suggesting that inositol is an essential metabolite. In yeast, inositol synthesis is highly regulated, and inositol levels have been shown to be a major metabolic regulator, with its abundance affecting the expression of hundreds of genes. Abnormalities in inositol metabolism have been associated with several human disorders. Despite its importance, very little is known about the regulation of inositol synthesis and the pathways regulated by inositol in human cells. The current study aimed to address this knowledge gap. Knockout of ISYNA1 (encoding myo-inositol-3-P synthase 1) in HEK293T cells generated a human cell line that is deficient in de novo inositol synthesis. ISYNA1-KO cells exhibited inositol-less death when deprived of inositol. Lipidomic analysis identified inositol deprivation as a global regulator of phospholipid levels in human cells, including downregulation of phosphatidylinositol (PI) and upregulation of the phosphatidylglycerol (PG)/cardiolipin (CL) branch of phospholipid metabolism. RNA-Seq analysis revealed that inositol deprivation induced substantial changes in the expression of genes involved in cell signaling, including extracellular signal-regulated kinase (ERK), and genes controlling amino acid transport and protein processing in the endoplasmic reticulum (ER). This study provides the first in-depth characterization of the effects of inositol deprivation on phospholipid metabolism and gene expression in human cells, establishing an essential role for inositol in maintaining cell viability and regulating cell signaling and metabolism.

Lipidomics profiles in hepatocytes from nonalcoholic steatohepatitis patients differ markedly from in vitro-induced steatotic hepatocytes.

Nonalcoholic steatohepatitis (NASH) is a severe form of liver injury that can be caused by a variety of stimuli and has a significant mortality rate. A common technique to induce in vitro steatosis involves culturing primary human hepatocytes (PHH) in fatty acid-enriched media. This study compared the lipidome of PHH cultured in fatty acid-enriched media to hepatocytes from patients with NASH and healthy controls. Hepatocytes from NASH patients displayed increased total cellular abundance of glycerolipids and phospholipids compared to healthy control hepatocytes. PHH cultured in fatty acid-enriched media demonstrated increased glycerolipids. However, these culture conditions did not induce elevated phospholipid levels. Thus, culturing PHH in fatty acid-enriched media has limited capacity to emulate the environment of hepatocytes in NASH patients.

In-vivo Anti-Diabetic Efficacy of Silver Nanoparticles from Marine Brown Seaweed Colpomenia sinuosa on Alloxan Stimulated Hyperglycemic Activity in Wistar Albino Rats

Diabetes mellitus is a chronic disease of the endocrine system characterized by elevated blood glucose levels, and disturbances in carbohydrate, fat and, protein metabolism. In the present study, the anti-diabetic efficacy of biosynthesized silver nanoparticles from marine brown seaweed Colpomenia sinuosa has been evaluated. The anti-diabetic effect of the silver nanoparticles biosynthesized from the Colpomenia sinuosa was assessed by inducing diabetes in the experimental Wistar albino rats through Alloxan monohydrate, a chemical that ultimately results in hyperglycemia (increase in the fasting blood sugar level) at a dosage of 50 mg/kg body weight given orally for about 28 days. The outcome of treatment with silver nanoparticles (50 mg/Kg i.p.) biosynthesized from Colpomenia sinuosa, were estimated using various biochemical parameters. The fasting blood glucose levels have reduced in the affected animals to near-normal levels. The retention of the level of the enzymes involved in diabetes, hematological analysis, decrease in the levels of total cholesterol, triglycerides, low-density lipoprotein, and phospholipids in the silver nanoparticles treated animals compared to the levels in normal control animals, exhibited significant anti-diabetic activity as compared to glipizide.

Interleukin-1 Induces the Release of Lubricating Phospholipids from Human Osteoarthritic Fibroblast-like Synoviocytes.

(1) Background: Synovial fluid (SF) from knee joints with osteoarthritis (OA) has increased levels of phospholipids (PL). We have reported earlier that TGF-ß and IGF-1 stimulate fibroblast-like synoviocytes (FLS) to synthesize increased amounts of PLs. The current study examined whether IL-1ß induces the release of PLs in FLS and the underlying mechanism. (2) Methods: Cultured human OA FLS were treated with IL-1ß alone and with pathway inhibitors or with synthetic liver X receptor (LXR) agonists. Cholesterol hydroxylases, ABC transporters, apolipoproteins (APO), LXR, sterol regulatory binding proteins (SREBPs), and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) were analyzed by RT-PCR, Western blot, and ELISA. The release of radiolabeled PLs from FLS was determined, and statistical analysis was performed using R (N = 5–9). (3) Results: Like synthetic LXR agonists, IL-1ß induced a 1.4-fold greater release of PLs from FLS. Simultaneously, IL-1ß upregulated the level of the PL transporter ABCA1 and of cholesterol hydroxylases CH25H and CYP7B1. IL-1ß and T0901317 stimulated the expression of SREBP1c, whereas only T0901317 enhanced SREBP2, HMGCR, APOE, LXRα, and ABCG1 additionally. (4) Conclusions: IL-1ß partially controls PL levels in OA-SF by affecting the release of PLs from FLS. Our data show that IL-1ß upregulates cholesterol hydroxylases and thus the formation of oxysterols, which, as natural agonists of LXR, increase the level of active ABCA1, in turn enhancing the release of PLs.

Long-term molecular differences between resilient and susceptible mice after a single traumatic exposure.

Post-traumatic stress disorder (PTSD) is a heterogeneous disorder induced by trauma, resulting in severe long-term impairments of an individual's mental health. PTSD does not develop in every individual and, thus, some individuals are more resilient. However, the underlying molecular mechanisms are poorly understood. Here, we aimed to elucidate these processes. We used a single-trauma PTSD model in mice to induce long-term maladaptive behaviours and profiled the mice 4weeks after trauma into resilient or susceptible individuals. The classification of phenotype was based on individual responses in different behavioural experiments. We analysed microbiome, circulating endocannabinoids, and long-term changes in brain phospholipid and transcript levels. We found many molecular differences between resilient and susceptible individuals across multiple molecular domains, including lipidome, transcriptome and gut microbiome. Some differences were stable even several weeks after the trauma, indicating the long-term impact of traumatic stimuli on the organism's physiology. Furthermore, the integration of these multilayered molecular data revealed that resilient and susceptible individuals have very distinct molecular signatures across various physiological systems. Trauma induced individual-specific behavioural responses that, in combination with a longitudinal characterisation of mice, could be used to identify distinct sub-phenotypes within the trauma-exposed group. These groups differed significantly not only in their behaviour but also in specific molecular aspects across a variety of tissues and brain regions. This approach may reveal new targets and predictive biomarkers for the pharmacological treatment and prognosis of stress-related disorders. This article is part of a themed issue on New discoveries and perspectives in mental and pain disorders. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.17/issuetoc.

Dietary Omega-3 Polyunsaturated Fatty-Acid Supplementation Upregulates Protective Cellular Pathways in Patients with Type 2 Diabetes Exhibiting Improvement in Painful Diabetic Neuropathy

Background: Omega-3 polyunsaturated fatty acids (PUFAs) have been proposed to improve chronic neuroinflammatory diseases in peripheral and central nervous systems. For instance, docosahexaenoic acid (DHA) protects nerve cells from noxious stimuli in vitro and in vivo. Recent reports link PUFA supplementation to improving painful diabetic neuropathy (pDN) symptoms, but cellular mechanisms responsible for this therapeutic effect are not well understood. The objective of this study is to identify distinct cellular pathways elicited by dietary omega-3 PUFA supplementation in patients with type 2 diabetes mellitus (T2DM) affected by pDN. Methods: Forty volunteers diagnosed with type 2 diabetes were enrolled in the “En Balance-PLUS” diabetes education study. The volunteers participated in weekly lifestyle/nutrition education and daily supplementation with 1000 mg DHA and 200 mg eicosapentaenoic acid. The Short-Form McGill Pain Questionnaire validated clinical determination of baseline and post-intervention pain complaints. Laboratory and untargeted metabolomics analyses were conducted using blood plasma collected at baseline and after three months of participation in the dietary regimen. The metabolomics data were analyzed using random forest, hierarchical clustering, ingenuity pathway analysis, and metabolic pathway mapping. Results: The data show that metabolites involved in oxidative stress and glutathione production shifted significantly to a more anti-inflammatory state post supplementation. Example of these metabolites include cystathionine (+90%), S-methylmethionine (+9%), glycine cysteine-glutathione disulfide (+157%) cysteinylglycine (+19%), glutamate (−11%), glycine (+11%), and arginine (+13.4%). In addition, the levels of phospholipids associated with improved membrane fluidity such as linoleoyl-docosahexaenoyl-glycerol (18:2/22:6) (+253%) were significantly increased. Ingenuity pathway analysis suggested several key bio functions associated with omega-3 PUFA supplementation such as formation of reactive oxygen species (p = 4.38 × 10−4, z-score = −1.96), peroxidation of lipids (p = 2.24 × 10−5, z-score = −1.944), Ca2+ transport (p = 1.55 × 10−4, z-score = −1.969), excitation of neurons (p = 1.07 ×10−4, z-score = −1.091), and concentration of glutathione (p = 3.06 × 10−4, z-score = 1.974). Conclusion: The reduction of pro-inflammatory and oxidative stress pathways following dietary omega-3 PUFA supplementation is consistent with the promising role of these fatty acids in reducing adverse symptoms associated with neuroinflammatory diseases and painful neuropathy.

The lipid transporter Mfsd2a maintains pulmonary surfactant homeostasis

Pulmonary surfactant is a lipoprotein complex essential for lung function, and insufficiency or altered surfactant composition is associated with major lung diseases, such as acute respiratory distress syndromes, idiopathic pulmonary fibrosis, and chronic obstructive pulmonary disease. Pulmonary surfactant is primarily composed of phosphatidylcholine (PC) in complex with specialized surfactant proteins and secreted by alveolar type 2 (AT2) cells. Surfactant homeostasis on the alveolar surface is balanced by the rates of synthesis and secretion with reuptake and recycling by AT2 cells, with some degradation by pulmonary macrophages and loss up the bronchial tree. However, whether phospholipid (PL) transporters exist in AT2 cells to mediate reuptake of surfactant PL remains to be identified. Here, we demonstrate that major facilitator superfamily domain containing 2a (Mfsd2a), a sodium-dependent lysophosphatidylcholine (LPC) transporter, is expressed at the apical surface of AT2 cells. A mouse model with inducible AT2 cell–specific deficiency of Mfsd2a exhibited AT2 cell hypertrophy with reduced total surfactant PL levels because of reductions in the most abundant surfactants, PC containing dipalmitic acid, and PC species containing the omega-3 fatty acid docosahexaenoic acid. These changes in surfactant levels and composition were mirrored by similar changes in the AT2 cell lipidome. Mechanistically, direct tracheal instillation of fluorescent LPC and PC probes indicated that Mfsd2a mediates the uptake of LPC generated by pulmonary phospholipase activity in the alveolar space. These studies reveal that Mfsd2a-mediated LPC uptake is quantitatively important in maintaining surfactant homeostasis and identify this lipid transporter as a physiological component of surfactant recycling.

Role of ACSL4 in the chemical-induced cell death in human proximal tubule epithelial HK-2 cells.

Acyl-CoA synthetase long-chain family member 4 (ACSL4) activates polyunsaturated fatty acids (PUFAs) to produce PUFA-derived acyl-CoAs, which are utilised for the synthesis of various biological components, including phospholipids (PLs). Although the roles of ACSL4 in non-apoptotic programmed cell death ferroptosis are well-characterised, its role in the other types of cell death is not fully understood. In the present study, we investigated the effects of ACSL4 knockdown on the levels of acyl-CoA, PL, and ferroptosis in the human normal kidney proximal tubule epithelial (HK-2) cells. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) analyses revealed that the knockdown of ACSL4 markedly reduced the levels of PUFA-derived acyl-CoA, but not those of other acyl-CoAs. In contrast with acyl-CoA levels, the docosahexaenoic acid (DHA)-containing PL levels were preferentially decreased in the ACSL4-knockdown cells compared with the control cells. Cell death induced by the ferroptosis inducers RSL3 and FIN56 was significantly suppressed by treatment with ferrostatin-1 or ACSL4 knockdown, and, unexpectedly, upon treating with a necroptosis inhibitor. In contrast, ACSL4 knockdown failed to suppress the other oxidative stress-induced cell deaths initiated by cadmium chloride and sodium arsenite. In conclusion, ACSL4 is involved in the biosynthesis of DHA-containing PLs in HK-2 cells and is specifically involved in the cell death induced by ferroptosis inducers.

Effects of Dietary Phospholipid and Cholesterol Levels on Growth, Molting Performance, and Ovary Development in Female Juvenile Crayfish (Procambarus clarkii)

The interaction between phospholipid (PL) and cholesterol (CH) on growth performance, molting rate, hepatopancreas fatty acid composition, and ovary development of the female red swamp crayfish (Procambarus clarkii) was investigated. Nine diets containing three PL levels (0, 20, and 60 g/kg) and three CH levels (0, 5, and 10 g/kg) were included in the study. Female crayfish (initial weight: 5.92 ± 0.03 g) were reared for 60 days. There was no significant interaction between dietary PL and CH levels ( P &gt; 0.05 ). However, the best growth performance and ovarian development were observed in crayfish receiving the 60 g/kg PL and 10 g/kg CH diet. High PL levels promoted CH transport in the hepatopancreas, and long-chain unsaturated fatty acid (C20:4n-6, C20:5n-3, and C22:6n-3) content of the hepatopancreas increased with the addition of PL in the diet. The molting rate increased with increasing CH levels in the diet containing 60 g/kg PL. Real-time quantitative polymerase chain reaction revealed that dietary CH enhanced the molting rate by improving the ecdysone receptor genes at transcription. This study showed that crayfish fed a diet containing 10 g/kg CH and 60 g/kg PL obtained maximum growth, molting rate, and ovary development.