Specific Lipid Molecules Research Articles

Omics-Integrated Approach (Metabolomics, Proteomics and Lipidomics) to Assess the Quality Control of Aquatic and Seafood Products

Since the demand for seafood products is growing and aquaculture provides more than fifty percent of the aquatic food as reported by FAO, the development of more accurate and sensitive analytical techniques in order to screen and evaluate the safety and quality of seafood products is needed. At this point, several omic techniques like proteomics, lipidomics, and metabolomics, or combinations of them, are used for integration into seafood processing and quality control. Moreover, according to the literature, using the respective techniques can prevent, control, and treat diseases in fish as well as address several issues in aquaculture. Proteomic techniques are used for the expression of proteins and their modifications. Metabolomic techniques are used for accurate identification of species, while lipidomics techniques are used for the identification of different or specific lipid molecules in fish species, as well as fatty acid composition and location distribution. This review is to cover the recent proteomics, metabolomics, and lipidomics studies on aquatic and seafood products in the areas of quality, safety, processing, and breeding of fish.

Sphingosine 1-phosphate receptor subtype 1 (S1P1) activity in the course of Alzheimer's disease

Some specific lipid molecules in the brain act as signaling molecules, neurotransmitters, or neuromodulators, by binding to specific G protein-coupled receptors (GPCR) for neurolipids. One such receptor, sphingosine 1-phosphate receptor subtype 1 (S1P1), is coupled to Gi/o proteins and is involved in cell proliferation, growth, and neuroprotection. S1P1 constitutes an interesting target for neurodegenerative diseases like multiple sclerosis and Alzheimer's disease (AD), in which changes in the sphingolipid metabolism have been observed. This study analyzes S1P1 receptor-mediated activity in healthy brains and during AD progression using postmortem samples from controls and patients at different Braak's stages. Additionally, the distribution of S1P1 receptor activity in human brains is compared to that in commonly used rodent models, rats and mice, through functional autoradiography, measuring [35S]GTPγS binding stimulated by the S1P1 receptor selective agonist CYM-5442 to obtain the distribution of functional activity of S1P1 receptors.S1P1 receptor-mediated activity, along with that of the cannabinoid CB1 receptor, is one of the highest recorded for any GPCR in many gray matter areas of the brain, reaching maximum values in the cerebellar cortex, specific areas of the hippocampus and the basal forebrain. S1P1 signaling is crucial in areas that regulate learning, memory, motor control, and nociception, such as the basal forebrain and basal ganglia. In AD, S1P1 receptor activity is increased in the inner layers of the frontal cortex and underlying cortical white matter at early stages, but decreases in the hippocampus in advanced stages, indicating ongoing brain impairment. Importantly, we identified significant correlations between S1P1 receptor activity and Braak stages, suggesting that S1P1 receptor dysfunction is associated to disease progression, particularly in memory-related regions. The S1P signaling via S1P1 receptor is a promising neurological target due to its role in key neurophysiological functions and its potential to modify the progression of neurodegenerative diseases. Finally, rats are suggested as a preferred experimental model for studying S1P1 receptor-mediated responses in the human brain.

Exploring the causal relationship between plasma lipids and varicose veins of lower extremity: A comprehensive two-sample Mendelian randomization study.

Varicose veins of the lower extremities (VVs) is a common chronic vascular disease, with high prevalence rates in some countries; however, their pathogenesis remains unclear. Some studies have identified associations between changes in specific plasma lipid molecules, such as phosphatidylethanolamine (PE), phosphatidylcholine (PC), and sphingomyelin (SM), and the onset of VVs, but due to confounders and reverse causality, the causal relationship remains unclear. Meanwhile, studies on the potential link between other plasma lipids beyond PE, PC, and SM and the risk of VVs in the lower extremities are lacking. This study aimed to explore the potential causal relationship between VVs and plasma lipid levels to provide theoretical insights into the interrelation of plasma lipids and VVs in their occurrence and progression. We conducted a two-sample Mendelian randomization (MR) analysis to assess the potential connection between genetically predicted levels of individual plasma lipids and the risk of developing VVs. We utilized data from a large-scale genome-wide association study involving 7174 Finnish individuals for 179 plasma lipidomes along with VVs genome-wide association study data from 408,455 UK individuals. MR analysis employed methods, such as inverse-variance weighting, weighted median, Bayesian Weighted Mendelian Randomization, and MR-Egger regression. The inverse-variance weighting method was primarily used to assess causality. The validity of the results was demonstrated through sensitivity analysis. In total, 12 lipids were found to have their plasma levels associated with an increased risk of VVs. This includes 3 types of PE, 7 types of PC, and 2 types of phosphatidylinositol. However, no significant causal relationship was found between the plasma levels of 11 types of SM and VVs. These results support the existence of a potential causal relationship between specific types of lipid levels and the risk of VVs, which can provide clues for further studies on biological mechanisms and the exploration of potential therapeutic targets.

Environmental Temperature Variation Affects Brain Lipid Composition in Adult Zebrafish (Danio rerio).

This study delves deeper into the impact of environmental temperature variations on the nervous system in teleost fish. Previous research has demonstrated that exposing adult zebrafish (Danio rerio) to 18 °C and 34 °C for 4 or 21 days induces behavioural changes compared to fish kept at a control temperature of 26 °C, suggesting alterations in the nervous system. Subsequent studies revealed that these temperature conditions also modify brain protein expression, indicating potential neurotoxic effects. The primary aim of this work was to investigate the effects of prolonged exposure (21 days) to 18 °C or 34 °C on the brain lipidomes of adult zebrafish compared to a control temperature. Analysis of the brain lipidome highlighted significant alteration in the relative abundances of specific lipid molecules at 18 °C and 34 °C, confirming distinct effects induced by both tested temperatures. Exposure to 18 °C resulted in an increase in levels of phospholipids, such as phosphatidylethanolamine, alongside a general reduction in levels of sphingolipids, including sphingomyelin. Conversely, exposure to 34 °C produced more pronounced effects, with increases in levels of phosphatidylethanolamine and those of various sphingolipids such as ceramide, gangliosides, and sphingomyelin, alongside a reduction in levels of ether phospholipids, including lysophosphatidylethanolamine ether, phosphatidylethanolamine ether, and phosphatidylglycerol ether, as well as levels of glycolipids like monogalactosyldiacylglycerol. These results, when integrated with existing proteomic and behavioural data, offer new insights into the effects of thermal variations on the nervous system in teleost fish. Specifically, our proteomic and lipidomic findings suggest that elevated temperatures may disrupt mitochondrial function, increase neuronal susceptibility to oxidative stress and cytotoxicity, alter axonal myelination, impair nerve impulse transmission, hinder synapse function and neurotransmitter release, and potentially lead to increased neuronal death. These findings are particularly relevant in the fields of cell biology, neurobiology, and ecotoxicology, especially in the context of global warming.

Clinical serum lipidomic profiling revealed potential lipid biomarkers for early diabetic retinopathy

Diabetic retinopathy (DR) is a serious complication of diabetes featuring abnormal lipid metabolism. However, the specific lipid molecules associated with onset and progression remain unclear. We used a broad-targeted lipidomics approach to assess the lipid changes that occur before the proliferative retinopathy stage and to identify novel lipid biomarkers to distinguish between patients without DR (NDR) and with non-proliferative DR (NPDR). Targeted lipomics analysis was carried out on serum samples from patients with type I diabetes, including 20 NDRs and 20 NPDRs. The results showed that compared with the NDR group, 102 lipids in the NPDR group showed specific expressions. Four lipid metabolites including TAG58:2-FA18:1 were obtained using the Least Absolute Shrink And Selection Operator (LASSO) and Support Vector Machine Recursive Feature Elimination (SVM-RFE) methods. The four-lipid combination diagnostic models showed good predictive ability in both the discovery and validation sets, and were able to distinguish between NDR patients and NPDR patients. The identified lipid markers significantly improved diagnostic accuracy within the NPDR group. Our findings help to better understand the complexity and individual differences of DR lipid metabolism.

Metabolism, fibrosis, and apoptosis: The effect of lipids and their derivatives on keloid formation.

Keloids, pathological scars resulting from skin trauma, have traditionally posed significant clinical management challenges due to their persistence and high recurrence rates. Our research elucidates the pivotal roles of lipids and their derivatives in keloid development, driven by underlying mechanisms of abnormal cell proliferation, apoptosis, and extracellular matrix deposition. Key findings suggest that abnormalities in arachidonic acid (AA) synthesis and non-essential fatty acid synthesis are integral to keloid formation. Further, a complex interplay exists between lipid derivatives, notably butyric acid (BA), prostaglandin E2 (PGE2), prostaglandin D2 (PGD2), and the regulation of hyperfibrosis. Additionally, combinations of docosahexaenoic acid (DHA) with BA and 15-deoxy-Δ12,14-Prostaglandin J2 have exhibited pronounced cytotoxic effects. Among sphingolipids, ceramide (Cer) displayed limited pro-apoptotic effects in keloid fibroblasts (KFBs), whereas sphingosine 1-phosphate (S1P) was found to promote keloid hyperfibrosis, with its analogue, FTY720, demonstrating contrasting benefits. Both Vitamin D and hexadecylphosphorylcholine (HePC) showed potential antifibrotic and antiproliferative properties, suggesting their utility in keloid management. While keloids remain a prevalent concern in clinical practice, this study underscores the promising potential of targeting specific lipid molecules for the advancement of keloid therapeutic strategies.

Lipid metabolic profiling and diagnostic model development for hyperlipidemic acute pancreatitis.

Hyperlipidemic acute pancreatitis (HLAP) is a form of pancreatitis induced by hyperlipidemia, posing significant diagnostic challenges due to its complex lipid metabolism disturbances. This study compared the serum lipid profiles of HLAP patients with those of a healthy cohort using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Orthogonal partial least squares discriminant analysis (OPLS-DA) was applied to identify distinct lipid metabolites. Logistic regression and LASSO regression were used to develop a diagnostic model based on the lipid molecules identified. A total of 393 distinct lipid metabolites were detected, impacting critical pathways such as fatty acid, sphingolipid, and glycerophospholipid metabolism. Five specific lipid molecules were selected to construct a diagnostic model, which achieved an area under the curve (AUC) of 1 in the receiver operating characteristic (ROC) analysis, indicating outstanding diagnostic accuracy. These findings highlight the importance of lipid metabolism disturbances in HLAP. The identified lipid molecules could serve as valuable biomarkers for HLAP diagnosis, offering potential for more accurate and early detection.

Orchestral role of lipid metabolic reprogramming in T-cell malignancy.

The immune function of normal T cells partially depends on the maneuvering of lipid metabolism through various stages and subsets. Interestingly, T-cell malignancies also reprogram their lipid metabolism to fulfill bioenergetic demand for rapid division. The rewiring of lipid metabolism in T-cell malignancies not only provides survival benefits but also contributes to their stemness, invasion, metastasis, and angiogenesis. Owing to distinctive lipid metabolic programming in T-cell cancer, quantitative, qualitative, and spatial enrichment of specific lipid molecules occur. The formation of lipid rafts rich in cholesterol confers physical strength and sustains survival signals. The accumulation of lipids through de novo synthesis and uptake of free lipids contribute to the bioenergetic reserve required for robust demand during migration and metastasis. Lipid storage in cells leads to the formation of specialized structures known as lipid droplets. The inimitable changes in fatty acid synthesis (FAS) and fatty acid oxidation (FAO) are in dynamic balance in T-cell malignancies. FAO fuels the molecular pumps causing chemoresistance, while FAS offers structural and signaling lipids for rapid division. Lipid metabolism in T-cell cancer provides molecules having immunosuppressive abilities. Moreover, the distinctive composition of membrane lipids has implications for immune evasion by malignant cells of T-cell origin. Lipid droplets and lipid rafts are contributors to maintaining hallmarks of cancer in malignancies of T cells. In preclinical settings, molecular targeting of lipid metabolism in T-cell cancer potentiates the antitumor immunity and chemotherapeutic response. Thus, the direct and adjunct benefit of lipid metabolic targeting is expected to improve the clinical management of T-cell malignancies.

Lipid Supplementation for Longevity and Gene Transcriptional Analysis in <em>Caenorhabditis elegans</em>

Aging is a complex process characterized by progressive physiological changes resulting from both environmental and genetic contributions. Lipids are crucial in constituting structural components of cell membranes, storing energy, and as signaling molecules. Regulation of lipid metabolism and signaling is essential to activate distinct longevity pathways. The roundworm Caenorhabditis elegans is an excellent and powerful organism to dissect the contribution of lipid metabolism and signaling in longevity regulation. Multiple research studies have described how diet supplementation of specific lipid molecules can extend C. elegans lifespan; however, minor differences in the supplementation conditions can cause reproducibility issues among scientists in different labs. Here, two detailed supplementation methods for C. elegans are reported employing lipid supplementation either with bacteria seeded on plates or bacterial suspension in liquid culture. Also provided herein are the details to perform lifespan assays with lifelong lipid supplementation and qRT-PCR analysis using a whole worm lysate or dissected tissues derived from a few worms. Using a combination of longitudinal studies and transcriptional investigations upon lipid supplementation, the feeding assays provide dependable approaches to dissect how lipids influence longevity and healthy aging. This methodology can also be adapted for various nutritional screening approaches to assess changes in a subset of transcripts using either a small number of dissected tissues or a few animals.

Effect of Diets on Plasma and Aorta Lipidome: A Study in the apoE Knockout Mouse Model.

Specific lipid molecules circulating in plasma at low concentrations have emerged as biomarkers of atherosclerotic risk. The aim of the present study is that of evaluating, in an athero-prone mouse model, how different diets can affect plasma and aorta lipidome. Thirty-six apoE knockout mice are divided in three groups and feed 12 weeks with diets differing for cholesterol and fatty acid content. Atherosclerosis is measured at the aortic sinus and aorta. Lipids are quantified in plasma and aorta with mass spectrometry. The cholesterol content of the diets is the main driver of lipid accumulation in plasma and aorta. The fatty acid composition of the diets affects plasma levels both of essential (linoleic acid) and nonessential (myristic and arachidonic acid) ones. Lipidomics show a comparable distribution, in plasma and aorta, of the main lipid components of oxidized LDL, including cholesteryl esters and lysophosphatidylcholines. Interestingly, lactosylceramide, glucosyl/galactosylceramide, and individual ceramide species are found to accumulate in diseased aortic segments. Both the cholesterol and fatty acid content of the diets profoundly affect plasma lipidome. Aorta lipidome is likewise affected with the accumulation of specific lipids known as markers of atherosclerosis.

Membrane Association Allosterically Regulates Phospholipase A2 Enzymes and Their Specificity.

Water-soluble proteins as well as membrane-bound proteins associate with membrane surfaces and bind specific lipid molecules in specific sites on the protein. Membrane surfaces include the traditional bilayer membranes of cells and subcellular organelles formed by phospholipids. Monolayer membranes include the outer monolayer phospholipid surface of intracellular lipid droplets of triglycerides and various lipoproteins including HDL, LDL, VLDL, and chylomicrons. These lipoproteins circulate in our blood and lymph systems and contain triglycerides, cholesterol, cholesterol esters, and proteins in their interior, and these are sometimes interspersed on their surfaces. Similar lipid-water interfaces also occur in mixed micelles of phospholipids and bile acids in our digestive system, which may also include internalized triglycerides and cholesterol esters. Diacyl phospholipids constitute the defining molecules of biological membranes. Phospholipase A1 (PLA1) hydrolyzes phospholipid acyl chains at the sn-1 position of membrane phospholipids, phospholipase A2 (PLA2) hydrolyzes acyl chains at the sn-2 position, phospholipase C (PLC) hydrolyzes the glycerol-phosphodiester bond, and phospholipase D (PLD) hydrolyzes the polar group-phosphodiester bond. Of the phospholipases, the PLA2s have been the most well studied at the mechanistic level. The PLA2 superfamily consists of 16 groups and numerous subgroups, and each is generally described as one of 6 types. The most well studied of the PLA2s include extensive genetic and mutational studies, complete lipidomics specificity characterization, and crystallographic structures. This Account will focus principally on results from deuterium exchange mass spectrometric (DXMS) studies of PLA2 interactions with membranes and extensive molecular dynamics (MD) simulations of their interactions with membranes and specific phospholipids bound in their catalytic and allosteric sites. These enzymes either are membrane-bound or are water-soluble and associate with membranes before extracting their phospholipid substrate molecule into their active site to carry out their enzymatic hydrolytic reaction. We present evidence that when a PLA2 associates with a membrane, the membrane association can result in a conformational change in the enzyme whereby the membrane association with an allosteric site on the enzyme stabilizes the enzyme in an active conformation on the membrane. We sometimes refer to this transition from a "closed" conformation in aqueous solution to an "open" conformation when associated with a membrane. The enzyme can then extract a single phospholipid substrate into its active site, and catalysis occurs. We have also employed DXMS and MD simulations to characterize how PLA2s interact with specific inhibitors that could lead to potential therapeutics. The PLA2s constitute a paradigm for how membranes interact allosterically with proteins, causing conformational changes and activation of the proteins to enable them to extract and bind a specific phospholipid from a membrane for catalysis, which is probably generalizable to intracellular and extracellular transport and phospholipid exchange processes as well as other specific biological functions. We will focus on the four main types of PLA2, namely, the secreted (sPLA2), cytosolic (cPLA2), calcium-independent (iPLA2), and lipoprotein-associated PLA2 (Lp-PLA2) also known as platelet-activating factor acetyl hydrolase (PAF-AH). Studies on a well-studied specific example of each of the four major types of the PLA2 superfamily demonstrate clearly that protein subsites can show precise specificity for one of the phospholipid hydrophobic acyl chains, often the one at the sn-2 position, including exquisite sensitivity to the number and position of double bonds.

Serum lipidomics profiles reveal potential lipid markers for prediabetes and type 2 diabetes in patients from multiple communities.

Dyslipidemia is a hallmark of diabetes mellitus (DM). However, specific lipid molecules closely associated with the initiation and progression of diabetes remain unclear. We used a pseudotargeted lipidomics approach to evaluate the complex lipid changes that occurred long before the diagnosis of type 2 diabetes mellitus (T2DM) and to identify novel lipid markers for screening prediabetes mellitus (PreDM) and T2DM in patients from multiple communities. Four hundred and eighty-one subjects consisting of T2DM, three subtypes of PreDM, and normal controls (NC) were enrolled as discovery cohort. Serum lipidomic profiles of 481 subjects were analyzed using an ultrahigh performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-QqQ-MS)-based pseudotargeted lipidomics method. The differential lipid molecules were further validated in an independent case-control study consisting of 150 PreDM, 234 T2DM and 94 NC. Multivariate discriminative analyses show that lipidomics data have considerable potential for identifying lipidome differences among T2DM, subtypes of PreDM and NC. Statistical associations of lipid (sub)species display significant variations in 11 lipid (sub)species levels for T2DM and distinctive differences in 8 lipid (sub)species levels between prediabetic and normoglycemic individuals, with further differences in 8 lipid (sub)species levels among subtypes of PreDM. Adjusted for sex, age and BMI, only two lipid (sub)species of fatty acid (FA) and phosphatidylcholine (PC) were associated at p< 0.05 for PreDM (all) and subtypes of PreDM. The defined lipid markers not only significantly improve the diagnostic accuracy of PreDM and T2DM but also effectively evaluating the risk of developing into each subtype of PreDM and T2DM when addition of age, sex, BMI, and FPG, respectively. Our findings improve insights into the lipid metabolic complexity and interindividual variations among subtypes of PreDM and T2DM, beyond the well-known differences in dyslipidemia in clinic.

A multimodal pipeline using NMR spectroscopy and MALDI-TOF mass spectrometry imaging from the same tissue sample.

NMR spectroscopy and matrix assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) are both commonly used to detect large numbers of metabolites and lipids in metabolomic and lipidomic studies. We have demonstrated a new workflow, highlighting the benefits of both techniques to obtain metabolomic and lipidomic data, which has realized for the first time the combination of these two complementary and powerful technologies. NMR spectroscopy is frequently used to obtain quantitative metabolite information from cells and tissues. Lipid detection is also possible with NMR spectroscopy, with changes being visible across entire classes of molecules. Meanwhile, MALDI MSI provides relative measures of metabolite and lipid concentrations, mapping spatial information of many specific metabolite and lipid molecules across cells or tissues. We have used these two complementary techniques in combination to obtain metabolomic and lipidomic measurements from triple-negative human breast cancer cells and tumor xenograft models. We have emphasized critical experimental procedures that ensured the success of achieving NMR spectroscopy and MALDI MSI in a combined workflow from the same sample. Our data show that several phospholipid metabolite species were differentially distributed in viable and necrotic regions of breast tumor xenografts. This study emphasizes the power of combined NMR spectroscopy-MALDI imaging to advance metabolomic and lipidomic studies.

Mammalian Epidermis: A Compendium of Lipid Functionality.

Mammalian epidermis is a striking example of the role of lipids in tissue biology. In this stratified epithelium, highly specialized structures are formed that leverage the hydrophobic properties of lipids to form an impermeable barrier and protect the humid internal environment of the body from the dry outside. This is achieved through tightly regulated lipid synthesis that generates the molecular species unique to the tissue. Beyond their fundamental structural role, lipids are involved in the active protection of the body from external insults. Lipid species present on the surface of the body possess antimicrobial activity and directly contribute to shaping the commensal microbiota. Lipids belonging to a variety of classes are also involved in the signaling events that modulate the immune responses to environmental stress as well as differentiation of the epidermal keratinocytes themselves. Recently, high-resolution methods are beginning to provide evidence for the involvement of newly identified specific lipid molecules in the regulation of epidermal homeostasis. In this review we give an overview of the wide range of biological functions of mammalian epidermal lipids.

Lipidomics Reveals Serum Specific Lipid Alterations in Diabetic Nephropathy.

In diabetes mellitus (DM), disorders of glucose and lipid metabolism are significant causes of the onset and progression of diabetic nephropathy (DN). However, the exact roles of specific lipid molecules in the pathogenesis of DN remain unclear. This study recruited 577 participants, including healthy controls (HCs), type-2 DM (2-DM) patients, and DN patients, from the clinic. Serum samples were collected under fasting conditions. Liquid chromatography-mass spectrometry-based lipidomics methods were used to explore the lipid changes in the serum and identify potential lipid biomarkers for the diagnosis of DN. Lipidomics revealed that the combination of lysophosphatidylethanolamine (LPE) (16:0) and triacylglycerol (TAG) 54:2-FA18:1 was a biomarker panel for predicting DN. The receiver operating characteristic analysis showed that the panel had a sensitivity of 89.1% and 73.4% with a specificity of 88.1% and 76.7% for discriminating patients with DN from HCs and 2-DM patients. Then, we divided the DN patients in the validation cohort into microalbuminuria (diabetic nephropathy at an early stage, DNE) and macroalbuminuria (diabetic nephropathy at an advanced stage, DNA) groups and found that LPE(16:0), phosphatidylethanolamine (PE) (16:0/20:2), and TAG54:2-FA18:1 were tightly associated with the stages of DN. The sensitivity of the biomarker panel to distinguish between patients with DNE and 2-DM, DNA, and DNE patients was 65.6% and 85.9%, and the specificity was 76.7% and 75.0%, respectively. Our experiment showed that the combination of LPE(16:0), PE(16:0/20:2), and TAG54:2-FA18:1 exhibits excellent performance in the diagnosis of DN.

Lipidomics reveals specific lipid molecules associated with cold stress syndrome in the Florida manatee (Trichechus manatus latirostris)

Cold stress syndrome (CSS) in the Florida manatee (Trichechus manatus latirostris) results in perturbations to many physiological pathways, often leading to further illness or death. In this study, we applied a non-targeted lipidomics approach with ultra-high performance liquid chromatography and high-resolution tandem mass spectrometry to characterize changes related to CSS in the lipidomic profiles of manatee plasma. Lipidomic analyses were conducted on healthy manatee (control) and cold-exposed manatee plasma samples with varying concentrations of Serum Amyloid A (SAA), an acute-phase protein that is associated with inflammatory disease. Control manatees (n = 10) were compared to all manatees exposed to cold temperatures (n = 17), and a subset of those manatees with SAA values > 120 μg/mL (n = 9). Increased SAA values were associated with higher levels of various acylcarnitine lipids, while several triacylglycerols and oxidized triacylglycerols were significantly lower in manatees with cold exposure. These identified lipids are critical molecules involved in the maintenance of energy homeostasis and could potentially be examined in conjunction with current physical parameters to characterize cold stress. The ability to detect such differences highlights the addition of lipidomics as a valuable tool in understanding cold stress and potentially other illnesses in manatees. Further investigation into the function of the altered lipids could greatly increase our understanding of lipid metabolism in physiologically stressed manatees as well as other marine mammals and inform future management recovery strategies.

Differential Expression of Sphingolipid Metabolizing Enzymes in Spontaneously Hypertensive Rats: A Possible Substrate for Susceptibility to Brain and Kidney Damage.

Alterations in the metabolism of sphingolipids, a class of biologically active molecules in cell membranes with direct effect on vascular homeostasis, are increasingly recognized as important determinant in different vascular disorders. However, it is not clear whether sphingolipids are implicated in the pathogenesis of hypertension-related cerebrovascular and renal damage. In this study, we evaluated the existence of possible abnormalities related to the sphingolipid metabolism in the brain and kidneys of two well validated spontaneously hypertensive rat strains, the stroke-prone (SHRSP) and the stroke-resistant (SHRSR) models, as compared to the normotensive Wistar Kyoto (WKY) rat strain. Our results showed a global alteration in the metabolism of sphingolipids in both cerebral and renal tissues of both hypertensive strains as compared to the normotensive rat. However, few defects, such as reduced expression of enzymes involved in the metabolism/catabolism of sphingosine-1-phosphate and in the de novo biosynthetic pathways, were exclusively detected in the SHRSP. Although further studies are necessary to fully understand the significance of these findings, they suggest that defects in specific lipid molecules and/or their related metabolic pathways may likely contribute to the pathogenesis of hypertensive target organ damage and may eventually serve as future therapeutic targets to reduce the vascular consequences of hypertension.

Speaking the language of lipids: the cross-talk between plants and pathogens in defence and disease.

Lipids and fatty acids play crucial roles in plant immunity, which have been highlighted over the past few decades. An increasing number of studies have shown that these molecules are pivotal in the interactions between plants and their diverse pathogens. The roles played by plant lipids fit in a wide spectrum ranging from the first physical barrier encountered by the pathogens, the cuticle, to the signalling pathways that trigger different immune responses and expression of defence-related genes, mediated by several lipid molecules. Moreover, lipids have been arising as candidate biomarkers of resistance or susceptibility to different pathogens. Studies on the apoplast and extracellular vesicles have been highlighting the possible role of lipids in the intercellular communication and the establishment of systemic acquired resistance during plant-pathogen interactions. From the pathogen perspective, lipid metabolism and specific lipid molecules play pivotal roles in the pathogen's life cycle completion, being crucial during recognition by the plant and evasion from the host immune system, therefore potentiating infection. Studies conducted in the last years have contributed to a better understanding of the language of lipids during the cross-talk between plants and pathogens. However, it is essential to continue exploring the knowledge brought up to light by transcriptomics and proteomics studies towards the elucidation of lipid signalling processes during defence and disease. In this review, we present an updated overview on lipids associated to plant-pathogen interactions, exploiting their roles from the two sides of this battle.

Membrane lipids under norm and pathology

Introduction. Lipid is an essential component of the cell and its organelles membrane. The uniqueness and selectivity of lipids to specific functions and asymmetry of lipid distribution in the organelle’s membrane give the cell ability of being highly qualified and specified. Aim. The paper provides a comprehensive review of membrane lipids in different tissues and organelles of the cell in norm and disease. Material and methods. The paper analyzed the present literature data on membrane lipids behavior in physiology and pathology. Analysis of the literature. The major structural and functional lipids of the cell membrane are phosphatidylcholine &gt; phosphatidylethanolamine. The absence/deficiency or augmentation of a specific type of lipid results in serious defects and usually life-threatening with a permanent disability. The observations discussed here suggest, the lipid peroxidation severity depends on the membrane lipid composition of the cell. Some tissue cells can handle lipoperoxidation and protect themselves from the peroxidation damaging products better, while other cells cannot compensate. Therefore, some organs are highly sensitive to peroxidation and irreversible changes occur rapidly. Conclusion. To sum up, the understanding of lipid’s role in norm and disease is clinically crucial to evaluate a novel therapeutic target to treat many metabolic disorders such as metabolic syndrome and some lysosomal storage disorders via targeting specific new signaling pathways, lipid molecules, and enzymes.

Exosomal miR-103-3p from LPS-activated THP-1 macrophage contributes to the activation of hepatic stellate cells.

Hepatic fibrosis occurs during chronic hepatic injury and is involved in hepatic stellate cells (HSCs) activated by several types of immune cells. Among the immune cells, hepatic macrophages and their crosstalk with HSCs play a vital role in all stages of hepatic fibrosis. Exosomes, which are 30-150nm lipid bilayer vehicles, can transfer specific lipid, nucleic acids, proteins, and other bioactive molecules. Exosomes can act as good communication between macrophages and HSCs. Herein, we investigated the role of exosomes between THP-1 macrophage and HSCs in the progression of liver fibrosis. Exosomes originating from lipopolysaccharide (LPS)-treated THP-1 macrophages promoted HSCs proliferation and induced the increased expression of fibrotic genes. LPS could alter the miRNA profile in exosomes secreted from THP-1 macrophages. The changed miR-103-3p in exosomes could promote HSCs proliferation and activation by targeting Krüppel-like factor 4 (KLF4) and it plays important roles in the crosstalk between THP-1 macrophages and HSCs during the progression of liver fibrosis. Moreover, miR-103-3p in serum exosomes from liver fibrosis patients could be a biomarker for liver fibrosis. Therefore, exosomes may have important roles in the crosstalk between macrophage and HSCs in the progression of chronic liver diseases.