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An over-active renin-angiotensin system (RAS) is characterized by elevated angiotensin II (Ang II). While Ang II can promote metabolic and mitochondrial dysfunction in tissues, little is known about its role in the gastrointestinal system (GI). Here, we treated rat primary colonic epithelial cells with Ang II (1–5000 nM) to better define their role in the GI. We hypothesized that Ang II would negatively affect mitochondrial bioenergetics as these organelles express Ang II receptors. Ang II increased cellular ATP production but reduced the mitochondrial membrane potential (MMP) of colonocytes. However, cells maintained mitochondrial oxidative phosphorylation and glycolysis with treatment, reflecting metabolic compensation with impaired MMP. To determine whether lipid dysregulation was evident, untargeted lipidomics were conducted. A total of 1949 lipids were detected in colonocytes spanning 55 distinct (sub)classes. Ang II (1 nM) altered the abundance of some sphingosines [So(d16:1)], ceramides [Cer-AP(t18:0/24:0)], and phosphatidylcholines [OxPC(16:0_20:5(2O)], while 100 nM Ang II altered some triglycerides and phosphatidylserines [PS(19:0_22:1). Ang II did not alter the relative expression of several enzymes in lipid metabolism; however, the expression of pyruvate dehydrogenase kinase 2 (PDK2) was increased, and PDK2 can be protective against dyslipidemia. This study is the first to investigate the role of Ang II in colonic epithelial cell metabolism. [ABSTRACT FROM AUTHOR]

Aβ peptides are known to bind neural plasma membranes in a process leading to the deposit of Aβ-enriched plaques. These extracellular structures are characteristic of Alzheimer's disease, the major cause of late-age dementia. The mechanisms of Aβ plaque formation and deposition are far from being understood. A vast number of studies in the literature describe the efforts to analyze those mechanisms using a variety of tools. The present review focuses on biophysical studies mostly carried out with model membranes or with computational tools. This review starts by describing basic physical aspects of lipid phases and commonly used model membranes (monolayers and bilayers). This is followed by a discussion of the biophysical techniques applied to these systems, mainly but not exclusively Langmuir monolayers, isothermal calorimetry, density-gradient ultracentrifugation, and molecular dynamics. The Methodological Section is followed by the core of the review, which includes a summary of important results obtained with each technique. The last section is devoted to an overall reflection and an effort to understand Aβ-bilayer binding. Concepts such as Aβ peptide membrane binding, adsorption, and insertion are defined and differentiated. The roles of membrane lipid order, nanodomain formation, and electrostatic forces in Aβ–membrane interaction are separately identified and discussed. [ABSTRACT FROM AUTHOR]

The barrier function of the skin is primarily determined by its outermost layer, the Stratum Corneum (SC). The SC consists of corneocytes embedded in a lipid matrix composed mainly of ceramides, cholesterol, and free fatty acids in equimolar proportions and is organised in a complex lamellar structure with different periodicities and lateral packings. This matrix provides a diffusion pathway across the SC for bioactive compounds that are administered to the skin. In this regard, and as the skin administration route has grown in popularity, there has been an increase in the use of lipid mixtures that closely resemble the SC lipid matrix, either for a deeper biophysical understanding or for pharmaceutical and cosmetic purposes. This review focuses on a systematic analysis of the main outcomes of using lipid mixtures as SC lipid matrix models for pharmaceutical and cosmetic purposes. Thus, a methodical evaluation of the main outcomes based on the SC structure is performed, as well as the main recent developments in finding suitable new in vitro tools for permeation testing based on lipid models. [ABSTRACT FROM AUTHOR]

Brain lipid homeostasis is an absolute requirement for proper functionality of nerve cells and neurological performance. Current evidence demonstrates that lipid alterations are linked to neurodegenerative diseases, especially Alzheimer's disease (AD). The complexity of the brain lipidome and its metabolic regulation has hampered the identification of critical processes associated with the onset and progression of AD. While most experimental studies have focused on the effects of known factors on the development of pathological hallmarks in AD, e.g., amyloid deposition, tau protein and neurofibrillary tangles, neuroinflammation, etc., studies addressing the causative effects of lipid alterations remain largely unexplored. In the present study, we have used a multifactor approach combining diets containing different amounts of polyunsaturated fatty acids (PUFAs), estrogen availabilities, and genetic backgrounds, i.e., wild type (WT) and APP/PS1 (FAD), to analyze the lipid phenotype of the frontal cortex in middle-aged female mice. First, we observed that severe n-3 PUFA deficiency impacts the brain n-3 long-chain PUFA (LCPUFA) composition, yet it was notably mitigated by hepatic de novo synthesis. n-6 LCPUFAs, ether-linked fatty acids, and saturates were also changed by the dietary condition, but the extent of changes was dependent on the genetic background and hormonal condition. Likewise, brain cortex phospholipids were mostly modified by the genotype (FAD>WT) with nuanced effects from dietary treatment. Cholesterol (but not sterol esters) was modified by the genotype (WT>FAD) and dietary condition (higher in DHA-free conditions, especially in WT mice). However, the effects of estrogen treatment were mostly observed in relation to phospholipid remodeling in a genotype-dependent manner. Analyses of lipid-derived variables indicate that nerve cell membrane biophysics were significantly affected by the three factors, with lower membrane microviscosity (higher fluidity) values obtained for FAD animals. In conclusion, our multifactor analyses revealed that the genotype, diet, and estrogen status modulate the lipid phenotype of the frontal cortex, both as independent factors and through their interactions. Altogether, the outcomes point to potential strategies based on dietary and hormonal interventions aimed at stabilizing the brain cortex lipid composition in Alzheimer's disease neuropathology. [ABSTRACT FROM AUTHOR]

Salt stress severely reduces photosynthetic efficiency, resulting in adverse effects on crop growth and yield production. Two key thylakoid membrane lipid components, monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG), were perturbed under salt stress. MGDG synthase 1 (MGD1) is one of the key enzymes for the synthesis of these galactolipids. To investigate the function of OsMGD1 in response to salt stress, the OsMGD1 overexpression (OE) and RNA interference (Ri) rice lines, and a wild type (WT), were used. Compared with WT, the OE lines showed higher chlorophyll content and biomass under salt stress. Besides this, the OE plants showed improved photosynthetic performance, including light absorption, energy transfer, and carbon fixation. Notably, the net photosynthetic rate and effective quantum yield of photosystem II in the OE lines increased by 27.5% and 25.8%, respectively, compared to the WT. Further analysis showed that the overexpression of OsMGD1 alleviated the negative effects of salt stress on photosynthetic membranes and oxidative defense by adjusting membrane lipid composition and fatty acid levels. In summary, OsMGD1-mediated membrane lipid remodeling enhanced salt tolerance in rice by maintaining membrane stability and optimizing photosynthetic efficiency. [ABSTRACT FROM AUTHOR]

The effects of combined short-term (3 days) exposure to Fusarium mycotoxins at both the EU recommended limit (T-2/HT-2 toxin: 0.25 mg/kg; DON/3-AcDON/15-AcDON: 5 mg/kg; FB1: 20 mg/kg) and twice the dose (T-2/HT-2 toxin: 0.5 mg/kg, DON/3-AcDON/15-AcDON: 10 mg/kg, and FB1: 40 mg/kg feed) on the kidneys of laying hens were examined. Our study aimed to investigate how these mycotoxins interacted with membrane lipid fatty acid (FA) composition and lipid peroxidation processes. It was observed that the levels of conjugated dienes and trienes were higher than the control in the low-mix group on day 3, and malondialdehyde concentration was higher on days 2 and 3. The proportion of phospholipid (PL) FAs showed that saturated and monounsaturated FAs increased. Still, both n3 and n6 polyunsaturated FAs decreased significantly on day 2 of exposure in the high-mix group. Among the n3 FAs, the level of docosahexaenoic (C22:6 n3) and among n6 FAs, arachidonic (C20:4 n6) acids decreased mainly on day 2 in the high-mix group. The results suggest that the combined exposure to Fusarium mycotoxins induced lipid peroxidation in the kidneys of laying hens, which resulted in marked changes in the PL FA profile. Histological examination revealed time- and dose-dependent increases as consequences of mycotoxin exposure. [ABSTRACT FROM AUTHOR]

Recently, artificial exosomes have been developed to overcome the challenges of natural exosomes, such as production scalability and stability. In the production of artificial exosomes, the incorporation of membrane proteins into lipid nanostructures is emerging as a notable approach for enhancing biocompatibility and treatment efficacy. This study focuses on incorporating HEK293T cell-derived membrane proteins into liposomes to create membrane-protein-bound liposomes (MPLCs), with the goal of improving their effectiveness as anticancer therapeutics. MPLCs were generated by combining two key elements: lipid components that are identical to those in conventional liposomes (CLs) and membrane protein components uniquely derived from HEK293T cells. An extensive comparison of CLs and MPLCs was conducted across multiple in vitro and in vivo cancer models, employing advanced techniques such as cryo-TEM (tramsmission electron microscopy) imaging and FT-IR (fourier transform infrared spectroscopy). MPLCs displayed superior membrane fusion capabilities in cancer cell lines, with significantly higher cellular uptake. Additionally, MPLCs maintained their morphology and size better than CLs when exposed to FBS (fetal bovine serum), suggesting enhanced serum stability. In a xenograft mouse model using HeLa and ASPC cancer cells, intravenous administration of MPLCs MPLCs accumulated more in tumor tissues, highlighting their potential for targeted cancer therapy. Overall, these results indicate that MPLCs have superior tumor-targeting properties, possibly attributable to their membrane protein composition, offering promising prospects for enhancing drug delivery efficiency in cancer treatments. This research could offer new clinical application opportunities, as it uses MPLCs with membrane proteins from HEK293T cells, which are known for their efficient production and compatibility with GMP (good manufacturing practice) standards. [ABSTRACT FROM AUTHOR]

Aegerolysins are a family of proteins that recognize and bind to specific membrane lipids or lipid domains; hence they can be used as membrane lipid sensors. Although aegerolysins are distributed throughout the tree of life, the most studied are those produced by the fungal genus Pleurotus. Most of the aegerolysin-producing mushrooms code also for proteins containing the membrane attack complex/perforin (MACPF)-domain. The combinations of lipid-sensing aegerolysins and MACPF protein partners are lytic for cells harboring the aegerolysin membrane lipid receptor and can be used as ecologically friendly bioinsecticides. In this work, we have recombinantly expressed four novel aegerolysin/MACPF protein pairs from the mushrooms Heterobasidion irregulare, Trametes versicolor, Mucidula mucida, and Lepista nuda, and compared these proteins with the already studied aegerolysin/MACPF protein pair ostreolysin A6–pleurotolysin B from P. ostreatus. We show here that most of these new mushroom proteins can form active aegerolysin/MACPF cytolytic complexes upon aegerolysin binding to membrane sphingolipids. We further disclose that these mushroom aegerolysins bind also to selected glycerophospholipids, in particular to phosphatidic acid and cardiolipin; however, these interactions with glycerophospholipids do not lead to pore formation. Our results indicate that selected mushroom aegerolysins show potential as new molecular biosensors for labelling phosphatidic acid. [ABSTRACT FROM AUTHOR]

Perturbations in bilayer material properties (thickness, lipid intrinsic curvature and elastic moduli) modulate the free energy difference between different membrane protein conformations, thereby leading to changes in the conformational preferences of bilayer-spanning proteins. To further explore the relative importance of curvature and elasticity in determining the changes in bilayer properties that underlie the modulation of channel function, we investigated how the micelle-forming amphiphiles Triton X-100, reduced Triton X-100 and the HII lipid phase promoter capsaicin modulate the function of alamethicin and gramicidin channels. Whether the amphiphile-induced changes in intrinsic curvature were negative or positive, amphiphile addition increased gramicidin channel appearance rates and lifetimes and stabilized the higher conductance states in alamethicin channels. When the intrinsic curvature was modulated by altering phospholipid head group interactions, however, maneuvers that promote a negative-going curvature stabilized the higher conductance states in alamethicin channels but destabilized gramicidin channels. Using gramicidin channels of different lengths to probe for changes in bilayer elasticity, we found that amphiphile adsorption increases bilayer elasticity, whereas altering head group interactions does not. We draw the following conclusions: first, confirming previous studies, both alamethicin and gramicidin channels are modulated by changes in lipid bilayer material properties, the changes occurring in parallel yet differing dependent on the property that is being changed; second, isolated, negative-going changes in curvature stabilize the higher current levels in alamethicin channels and destabilize gramicidin channels; third, increases in bilayer elasticity stabilize the higher current levels in alamethicin channels and stabilize gramicidin channels; and fourth, the energetic consequences of changes in elasticity tend to dominate over changes in curvature. [ABSTRACT FROM AUTHOR]

Using the gramicidin A channel as a molecular probe, we show that tubulin binding to planar lipid membranes changes the channel kinetics—seen as an increase in the lifetime of the channel dimer—and thus points towards modification of the membrane's mechanical properties. The effect is more pronounced in the presence of non-lamellar lipids in the lipid mixture used for membrane formation. To interpret these findings, we propose that tubulin binding redistributes the lateral pressure of lipid packing along the membrane depth, making it closer to the profile expected for lamellar lipids. This redistribution happens because tubulin perturbs the lipid headgroup spacing to reach the membrane's hydrophobic core via its amphiphilic α-helical domain. Specifically, it increases the forces of repulsion between the lipid headgroups and reduces such forces in the hydrophobic region. We suggest that the effect is reciprocal, meaning that alterations in lipid bilayer mechanics caused by membrane remodeling during cell proliferation in disease and development may also modulate tubulin membrane binding, thus exerting regulatory functions. One of those functions includes the regulation of protein–protein interactions at the membrane surface, as exemplified by VDAC complexation with tubulin. [ABSTRACT FROM AUTHOR]

Single-chain lipid amphiphiles such as fatty acids and monoglycerides are promising antimicrobial alternatives to replace industrial surfactants for membrane-enveloped pathogen inhibition. Biomimetic lipid membrane platforms in combination with label-free biosensing techniques offer a promising route to compare the membrane-disruptive properties of different fatty acids and monoglycerides individually and within mixtures. Until recently, most related studies have utilized planar model membrane platforms, and there is an outstanding need to investigate how antimicrobial lipid mixtures disrupt curved model membrane platforms such as intact vesicle adlayers that are within the size range of membrane-enveloped virus particles. This need is especially evident because certain surfactants that completely disrupt planar/low-curvature membranes are appreciably less active against high-curvature membranes. Herein, we conducted quartz crystal microbalance–dissipation (QCM-D) measurements to investigate the membrane-disruptive properties of glycerol monolaurate (GML) monoglyceride and lauric acid (LA) fatty acid mixtures to rupture high-curvature, ~75 nm diameter lipid vesicle adlayers. We identified that the vesicle rupture activity of GML/LA mixtures mainly occurred above the respective critical micelle concentration (CMC) of each mixture, and that 25/75 mol% GML/LA micelles exhibited the greatest degree of vesicle rupture activity with ~100% efficiency that exceeded the rupture activity of other tested mixtures, individual compounds, and past reported values with industrial surfactants. Importantly, 25/75 GML/LA micelles outperformed 50/50 GML/LA micelles, which were previously reported to have the greatest membrane-disruptive activity towards planar model membranes. We discuss the mechanistic principles behind how antimicrobial lipid engineering can influence membrane-disruptive activity in terms of optimizing the balance between competitive membrane remodeling processes and inducing anisotropic vs. isotropic spontaneous curvature in lipid membrane systems. [ABSTRACT FROM AUTHOR]

Deciphering the origins of life on a molecular level includes unravelling the numerous interactions that could occur between the most important biomolecules being the lipids, peptides and nucleotides. They were likely all present on the early Earth and all necessary for the emergence of cellular life. In this study, we intended to explore conditions that were at the same time conducive to chemical reactions critical for the origins of life (peptide–oligonucleotide couplings and templated ligation of oligonucleotides) and compatible with the presence of prebiotic lipid vesicles. For that, random peptides were generated from activated amino acids and analysed using NMR and MS, whereas short oligonucleotides were produced through solid-support synthesis, manually deprotected and purified using HPLC. After chemical activation in prebiotic conditions, the resulting mixtures were analysed using LC-MS. Vesicles could be produced through gentle hydration in similar conditions and observed using epifluorescence microscopy. Despite the absence of coupling or ligation, our results help to pave the way for future investigations on the origins of life that may gather all three types of biomolecules rather than studying them separately, as it is still too often the case. [ABSTRACT FROM AUTHOR]

Nanovesicles produced with lipids and polymers are promising devices for drug and bioactive delivery and are of great interest in pharmaceutical applications. These nanovesicles can be engineered for improvement in bioavailability, patient compliance or to provide modified release or enhanced delivery. However, their applicability strongly depends on the safety and low immunogenicity of the components. Despite this, the use of unsaturated lipids in nanovesicles, which degrade following oxidation processes during storage and especially during the proper routes of administration in the human body, may yield toxic degradation products. In this study, we used a biopolymer (chitosan) labeled with flavonoid (catechin) as a component over a lipid bilayer for micro- and nanovesicles and characterized the structure of these vesicles in oxidation media. The purpose of this was to evaluate the in situ effect of the antioxidant in three different vesicular systems of medium, low and high membrane curvature. Liposomes and giant vesicles were produced with the phospholipids DOPC and POPC, and crystalline cubic phase with monoolein/DOPC. Concentrations of chitosan–catechin (CHCa) were included in all the vesicles and they were challenged in oxidant media. The cytotoxicity analysis using the MTT assay (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) revealed that concentrations of CHCa below 6.67 µM are non-toxic to HeLa cells. The size and zeta potential of the liposomes evidenced the degradation of their structures, which was minimized by CHCa. Similarly, the membrane of the giant vesicle, which rapidly deteriorated in oxidative solution, was protected in the presence of CHCa. The production of a lipid/CHCa composite cubic phase revealed a specific cubic topology in small-angle X-ray scattering, which was preserved in strong oxidative media. This study demonstrates the specific physicochemical characteristics introduced in the vesicular systems related to the antioxidant CHCa biopolymer, representing a platform for the improvement of composite nanovesicle applicability. [ABSTRACT FROM AUTHOR]

The lanthanide metal gadolinium has been used in the healthcare industry as a paramagnetic contrast agent for years. Gadolinium deposition in brain tissue and kidneys has been reported following gadolinium-based contrast agent administration to patients undergoing MRI. This study demonstrates the detrimental effects of gadolinium exposure at the level of the cell membrane. Biophysical analysis using fluorescence spectroscopy and dynamic light scattering illustrates differential interactions of gadolinium ions with key classes of brain membrane lipids, including phosphatidylcholines and sphingomyelins, as well as brain polar extracts and biomimetic brain model membranes. Electrostatic attraction to negatively charged lipids like phosphatidylserine facilitates metal complexation but zwitterionic phosphatidylcholine and sphingomyelin interaction was also significant, leading to membrane rigidification and increases in liposome size. Effects were stronger for fully saturated over monounsaturated acyl chains. The metal targets key lipid classes of brain membranes and these biophysical changes could be very detrimental in biological membranes, suggesting that the potential negative impact of gadolinium contrast agents will require more scientific attention. [ABSTRACT FROM AUTHOR]

Reduced sperm motility and/or count are among the major causes of reduced fertility in men, and sperm membranes play an important role in the spermatogenesis and fertilization processes. However, the impact of sperm lipid composition on male fertility remains under-investigated. The aim of the present study was to perform a lipidomic analysis of human sperm membranes: we performed an untargeted analysis of membrane lipid composition in fertile (N = 33) and infertile subjects (N = 29). In parallel, we evaluated their serum lipid levels. Twenty-one lipids were identified by their mass/charge ratio and post-source decay spectra. Sulfogalactosylglycerolipid (SGG, seminolipid) was the most abundant lipid component in the membranes. In addition, we observed a significant proportion of PUFAs. Important differences have emerged between the fertile and infertile groups, leading to the identification of a lipid cluster that was associated with semen parameters. Among these, cholesterol sulfate, SGG, and PUFAs represented the most important predictors of semen quality. No association was found between the serum and sperm lipids. Dietary PUFAs and SGG have acknowledged antioxidant functions and could, therefore, represent sensitive markers of sperm quality and testicular function. Altogether, these results underline the important role of sperm membrane lipids, which act independently of serum lipids levels and may rather represent an independent marker of reproductive function. [ABSTRACT FROM AUTHOR]

Needle abscission in balsam fir has been linked to both cold acclimation and changes in lipid composition. The overall objective of this research is to uncover lipid changes in balsam fir during cold acclimation and link those changes with postharvest abscission. Branches were collected monthly from September to December and were assessed for cold tolerance via membrane leakage and chlorophyll fluorescence changes at −5, −15, −25, −35, and −45 °C. Lipids were extracted and analyzed using mass spectrometry while postharvest needle abscission was determined gravimetrically. Cold tolerance and needle retention each significantly (p < 0.001) improved throughout autumn in balsam fir. There were concurrent increases in DGDG, PC, PG, PE, and PA throughout autumn as well as a decrease in MGDG. Those same lipids were strongly related to cold tolerance, though MGDG had the strongest relationship (R2 = 55.0% and 42.7% from membrane injury and chlorophyll fluorescence, respectively). There was a similar, albeit weaker, relationship between MGDG:DGDG and needle retention (R2 = 24.3%). Generally, a decrease in MGDG:DGDG ratio resulted in better cold tolerance and higher needle retention in balsam fir, possibly due to increased membrane stability. This study confirms the degree of cold acclimation in Nova Scotian balsam fir and presents practical significance to industry by identifying the timing of peak needle retention. It is suggested that MGDG:DGDG might be a beneficial tool for screening balsam fir genotypes with higher needle retention characteristics. [ABSTRACT FROM AUTHOR]

Biological membranes, primarily composed of lipids, envelop each living cell. The intricate composition and organization of membrane lipids, including the variety of fatty acids they encompass, serve a dynamic role in sustaining cellular structural integrity and functionality. Typically, modifications in lipid composition coincide with consequential alterations in universally significant signaling pathways. Exploring the various fatty acids, which serve as the foundational building blocks of membrane lipids, provides crucial insights into the underlying mechanisms governing a myriad of cellular processes, such as membrane fluidity, protein trafficking, signal transduction, intercellular communication, and the etiology of certain metabolic disorders. Furthermore, comprehending how alterations in the lipid composition, especially concerning the fatty acid profile, either contribute to or prevent the onset of pathological conditions stands as a compelling area of research. Hence, this review aims to meticulously introduce the intricacies of membrane lipids and their constituent fatty acids in a healthy organism, thereby illuminating their remarkable diversity and profound influence on cellular function. Furthermore, this review aspires to highlight some potential therapeutic targets for various pathological conditions that may be ameliorated through dietary fatty acid supplements. The initial section of this review expounds on the eukaryotic biomembranes and their complex lipids. Subsequent sections provide insights into the synthesis, membrane incorporation, and distribution of fatty acids across various fractions of membrane lipids. The last section highlights the functional significance of membrane-associated fatty acids and their innate capacity to shape the various cellular physiological responses. [ABSTRACT FROM AUTHOR]

Accelerated storage is routinely used with pharmaceuticals to predict stability and degradation patterns over time. The aim of this is to assess the shelf life and quality under harsher conditions, providing crucial insights into their long-term stability and potential storage issues. This study explores the potential of transferring this approach to food matrices for shelf-life estimation. Therefore, hazelnuts were stored under accelerated short-term and realistic long-term conditions. Subsequently, they were analyzed with high resolution mass spectrometry, focusing on the lipid profile. LC-MS analysis has shown that many unique processes take place under accelerated conditions that do not occur or occur much more slowly under realistic conditions. This mainly involved the degradation of membrane lipids such as phospholipids, ceramides, and digalactosyldiacylglycerides, while oxidation processes occurred at different rates in both conditions. It can be concluded that a food matrix is far too complex and heterogeneous compared to pharmaceuticals, so that many more processes take place during accelerated storage, which is why the results cannot be used to predict molecular changes in hazelnuts stored under realistic conditions. [ABSTRACT FROM AUTHOR]

Mitochondria are highly dynamic organelles that constantly undergo fusion and fission events to maintain their shape, distribution and cellular function. Mitofusin 1 and 2 proteins are two dynamin-like GTPases involved in the fusion of outer mitochondrial membranes (OMM). Mitofusins are anchored to the OMM through their transmembrane domain and possess two heptad repeat domains (HR1 and HR2) in addition to their N-terminal GTPase domain. The HR1 domain was found to induce fusion via its amphipathic helix, which interacts with the lipid bilayer structure. The lipid composition of mitochondrial membranes can also impact fusion. However, the precise mode of action of lipids in mitochondrial fusion is not fully understood. In this study, we examined the role of the mitochondrial lipids phosphatidylethanolamine (PE), cardiolipin (CL) and phosphatidic acid (PA) in membrane fusion induced by the HR1 domain, both in the presence and absence of divalent cations (Ca2+ or Mg2+). Our results showed that PE, as well as PA in the presence of Ca2+, effectively stimulated HR1-mediated fusion, while CL had a slight inhibitory effect. By considering the biophysical properties of these lipids in the absence or presence of divalent cations, we inferred that the interplay between divalent cations and specific cone-shaped lipids creates regions with packing defects in the membrane, which provides a favorable environment for the amphipathic helix of HR1 to bind to the membrane and initiate fusion. [ABSTRACT FROM AUTHOR]

The thyroid gland is the primary site of sodium/iodide symporter (NIS), an intrinsic plasma membrane protein responsible for the active uptake of iodine, which is indispensable for thyroid hormone synthesis. Since exposure of the thyroid to NIS inhibitors can potentially have harmful effects on the entire organism, it is important to investigate the potential protective effects of known antioxidants, such as melatonin and indole-3-propionic acid (IPA), against pro-oxidative action of classic NIS inhibitors. The study aimed to check if and to what extent melatonin and IPA interact with some confirmed NIS inhibitors regarding their effects on oxidative damage to membrane lipids in the thyroid. For comparison with the thyroid gland, in which NIS is typically present, the liver tissue—not possessing NIS—was applied in the present study. Thyroid and liver homogenates were incubated in the presence of tested NIS inhibitors (i.e., NaClO3, NH4SCN, KSeCN, KNO3, NaF, KClO4, and BPA) in different ranges of concentrations with/without melatonin (5 mM) or IPA (5 mM). The malondialdehyde+4-hydroxyalkenals (MDA + 4-HDA) concentration (LPO index) was measured spectrophotometrically. NaClO3 increased LPO in the thyroid and in the liver, but these pro-oxidative effects were not prevented by either melatonin or IPA. Instead, pro-oxidative effects of NH4SCN observed in both tissues were prevented by both indole substances. KSeCN and NaF increased LPO only in the thyroid, and these pro-oxidative effects were prevented by melatonin and IPA. KNO3, KClO4, and BPA did not increase LPO, which can be due to their low concentrations resulting from restricted solubility. In conclusion, as melatonin prevented oxidative damage to membrane lipids in the thyroid caused by some sodium/iodide symporter inhibitors, this indoleamine shoud be considered as a potential protective agent when produced appropriately in living organisms but also as an exogenous substance recommended to individuals overexposed to NIS inhibitors. [ABSTRACT FROM AUTHOR]

Follicular fluid (FF) ensures a safe environment for oocyte growth and maturation inside the ovarian follicle in mammals. In each cycle, the large dominant follicle (LF) contains the oocyte designated to be ovulated, whereas the small subordinate follicles (SFs) of the same wave will die through atresia. In cows, the oocytes from the SF, being 2 mm in size, are suitable for in vitro reproduction biotechnologies, and their competence in developing an embryo depends on the size of the follicles. FF contains proteins, metabolites, fatty acids, and a multitude of extracellular vesicles (ffEVs) of different origins, which may influence oocyte competence through bidirectional exchanges of specific molecular cargo between follicular cells and enclosed oocytes. FF composition evolves along with follicle growth, and the abundance of different lipids varies between the LF and SF. Here, significant differences in FF lipid content between the LFs and SFs within the same ovary were demonstrated by MALD-TOF mass spectrometry imaging on bovine ovarian sections. We then aimed to enlighten the lipid composition of FF, and MALDI-TOF lipid profiling was performed on cellular, vesicular, and liquid fractions of FF. Differential analyses on the abundance of detected lipid features revealed specific enrichment of phospholipids in different ffEV types, such as microvesicles (MVs) and exosomes (Exo), compared to depleted FF. MALDI-TOF lipid profiling on MVs and Exo from the LF and SF samples (n = 24) revealed that more than 40% of detected features were differentially abundant between the groups of MVs and Exo from the different follicles (p < 0.01, fold change > 2). Glycerophospholipid and sphingolipid features were more abundant in ffEVs from the SFs, whereas different lysophospholipids, including phosphatidylinositols, were more abundant in the LFs. As determined by functional analysis, the specific lipid composition of ffEVs suggested the involvement of vesicular lipids in cell signaling pathways and largely contributed to the differentiation of the dominant and subordinate follicles. [ABSTRACT FROM AUTHOR]

Soy lecithin (SL) is a source of phospholipids, which play a crucial role in determining cell membrane structure, fluidity, and functionality. This study investigated the effects of dietary SL on the performance, nutrient digestibility, and body composition of Nile tilapia juveniles (average initial weight 12.2 g) raised at 22 °C. The experimental diets contained increasing levels of SL (0.0, 21.0, 43.0, and 64.0 g kg−1). The best weight gain and feed efficiency occurred with 42.2 and 49.8 g kg−1 of SL inclusion, respectively, estimated through quadratic regression after 90 days of feeding. The body composition of the fish was also affected by feeding with SL, with a decrease in total body lipids and viscerosomatic and hepatosomatic indices but an increase in polyunsaturated fatty acids. A digestibility trial using only two diets (0SLD and 43SLD) revealed increased lipid and fatty acids digestibility in fish fed with 43SLD. In addition, the consumption of digestible nutrients was the highest in fish fed the diet 43SL. Therefore, SL supplementation is beneficial in fall/spring diets for Nile tilapia juveniles as it can improve growth, lipid digestibility, and body composition when supplemented within the range of 42 to 50 g kg−1 diet. [ABSTRACT FROM AUTHOR]

To examine the effects of membrane charge, the electrolyte species and glycosyl on the distribution of negatively charged radical of superoxide anion (·O2−) around the cell membrane, different phospholipid bilayer systems containing ·O2− radicals, different electrolytes and phospholipid bilayers were constructed through Charmm-GUI and Amber16. These systems were equilibrated with molecular dynamics by using Gromacs 5.0.2 to analyze the statistical behaviors of ·O2− near the lipid membrane under different conditions. It was found that in the presence of potassium rather than sodium, the negative charge of the phospholipid membrane is more likely to rarefy the superoxide anion distribution near the membrane surface. Further, the presence of glycosyl significantly reduced the density of ·O2− near the phospholipid bilayer by 78.3% compared with that of the neutral lipid membrane, which may have a significant contribution to reducing the lipid peroxidation from decreasing the ·O2− density near the membrane. [ABSTRACT FROM AUTHOR]

Low-temperature semen storage technologies are already being used in poultry conservation programs, but the quality of reproductive material stored in cryobanks varies greatly and cannot always be successfully used for practical purposes. Therefore, it is necessary to improve the compositions of cryoprotective media to improve their quality. This study aimed to investigate the composition of membrane lipids and carbohydrates in the cytosol of rooster spermatozoa, to explain the dose-dependent effect of a combination of trehalose and fructose in cryoprotective media on the preservation of their morphological and kinetic parameters during freezing/thawing, and to determine the most effective diluent composition. Ejaculates were collected from Rhode Island Red roosters (n = 10). The effectiveness of three diluents containing trehalose was evaluated: LCM-control (0 mM), Treh20 (9.5 mM), and Treh30 (13.4 mM). Chromatographic analysis of membrane lipids, carbohydrates, and polyols of the spermatozoa cytosol was performed. A decrease in the content of glycolipids in the plasma membranes of spermatozoa from 2.0% in native spermatozoa to 1.1–1.4% (frozen/thawed) and phospholipids from 71.2% (native) to 70.5% (frozen/thawed) reduced the progressive sperm motility from 65.7% in native spermatozoa to 12.6–27.6% (frozen/thawed). The same dynamics were observed for the viability parameter of 90.4% (native) and 27.0–41.2% (frozen/thawed). The Treh20 diluent, using a combination of fructose (36 mM) and trehalose (9.5 mM) saccharides, maximally preserved the lipid profile of plasma membranes and the composition of the cytosol of frozen/thawed rooster spermatozoa, which positively affected the indicators of general and progressive mobility and viability. [ABSTRACT FROM AUTHOR]

This paper reports on an NMR metabolomics study of lipophilic extracts of Ruditapes philippinarum clams exposed to the hormonal contaminant 17-α-ethinylestradiol (EE2), at 17 °C and 21 °C. The results reveal that exposure at 17 °C triggers a weak response at low EE2 concentrations, suggestive of a slight increase in membrane rigidity, followed by lipid metabolic stability at higher EE2 concentrations. On the other hand, at 21 °C, lipid metabolism begins to respond at 125 ng/L EE2, with antioxidant docosahexaenoic acid (DHA) helping to tackle high-oxidative-stress conditions, in tandem with enhanced storage of triglycerides. Exposure to 625 ng/L EE2 (highest concentration) enhances phosphatidylcholine (PtdCho) and polyunsaturated fatty acid (PUFA) levels, their direct intercorrelation suggesting PUFA incorporation in new membrane phospholipids. This should lead to increased membrane fluidity, probably aided by a decrease in cholesterol. PUFA levels, considered a measure of membrane fluidity, were strongly (and positively) correlated to intracellular glycine levels, thus identifying glycine as the main osmolyte entering the cells under high stress. Membrane fluidity also seems to elicit the loss of taurine. This work contributes to the understanding of the mechanisms of response of R. philippinarum clams to EE2 in tandem with warming while unveiling novel potential markers of stress mitigation, namely high levels of PtdCho, PUFAs (or PtdCho/glycerophosphocholine and PtdCho/acetylcholine ratios) and linoleic acid and low PUFA/glycine ratios. [ABSTRACT FROM AUTHOR]

α-Tocopherol-13′-carboxychromanol (α-T-13′-COOH) is an endogenously formed bioactive α-tocopherol metabolite that limits inflammation and has been proposed to exert lipid metabolism-regulatory, pro-apoptotic, and anti-tumoral properties at micromolar concentrations. The mechanisms underlying these cell stress-associated responses are, however, poorly understood. Here, we show that the induction of G0/G1 cell cycle arrest and apoptosis in macrophages triggered by α-T-13′-COOH is associated with the suppressed proteolytic activation of the lipid anabolic transcription factor sterol regulatory element-binding protein (SREBP)1 and with decreased cellular levels of stearoyl-CoA desaturase (SCD)1. In turn, the fatty acid composition of neutral lipids and phospholipids shifts from monounsaturated to saturated fatty acids, and the concentration of the stress-preventive, pro-survival lipokine 1,2-dioleoyl-sn-glycero-3-phospho-(1′-myo-inositol) [PI(18:1/18:1)] decreases. The selective inhibition of SCD1 mimics the pro-apoptotic and anti-proliferative activity of α-T-13′-COOH, and the provision of the SCD1 product oleic acid (C18:1) prevents α-T-13′-COOH-induced apoptosis. We conclude that micromolar concentrations of α-T-13′-COOH trigger cell death and likely also cell cycle arrest by suppressing the SREBP1-SCD1 axis and depleting cells of monounsaturated fatty acids and PI(18:1/18:1). [ABSTRACT FROM AUTHOR]

Membrane proteins play an important role in key cellular functions, such as signal transduction, apoptosis, and metabolism. Therefore, structural and functional studies of these proteins are essential in fields such as fundamental biology, medical science, pharmacology, biotechnology, and bioengineering. However, observing the precise elemental reactions and structures of membrane proteins is difficult, despite their functioning through interactions with various biomolecules in living cells. To investigate these properties, methodologies have been developed to study the functions of membrane proteins that have been purified from biological cells. In this paper, we introduce various methods for creating liposomes or lipid vesicles, from conventional to recent approaches, as well as techniques for reconstituting membrane proteins into artificial membranes. We also cover the different types of artificial membranes that can be used to observe the functions of reconstituted membrane proteins, including their structure, number of transmembrane domains, and functional type. Finally, we discuss the reconstitution of membrane proteins using a cell-free synthesis system and the reconstitution and function of multiple membrane proteins. [ABSTRACT FROM AUTHOR]

Plants have evolved various mechanisms for low P tolerance, one of which is changing their membrane lipid composition by remodeling phospholipids with non-phospholipids. The objective of this study was to investigate the remodeling of membrane lipids among rice cultivars under P deficiency. Rice (Oryza sativa L.) cultivars (Akamai, Kiyonishiki, Akitakomachi, Norin No. 1, Hiyadateine, Koshihikari, and Netaro) were grown in 0 (−P) and 8 (+P) mg P L−1 solution cultures. Shoots and roots were collected 5 and 10 days after transplanting (DAT) in solution culture and subjected to lipidome profiling using liquid chromatography-mass spectrometry. Phosphatidylcholine (PC)34, PC36, phosphatidylethanolamine (PE)34, PE36, phosphatidylglycerol (PG)34, phosphatidylinositol (PI)34 were the major phospholipids and digalactosyldiacylglycerol (DGDG)34, DGDG36, 1,2-diacyl-3-O-alpha-glucuronosylglycerol (GlcADG)34, GlcADG36, monogalactosyldiacylglycerol (MGDG)34, MGDG36, sulfoquinovosyldiacylglycerol (SQDG)34 and SQDG36 were the major non-phospholipids. Phospholipids were lower in the plants that were grown under −P conditions than that in the plants that were grown under +P for all cultivars at 5 and 10 DAT. The levels of non-phospholipids were higher in −P plants than that in +P plants of all cultivars at 5 and 10 DAT. Decomposition of phospholipids in roots at 5 DAT correlated with low P tolerance. These results suggest that rice cultivars remodel membrane lipids under P deficiency, and the ability of remodeling partly contributes to low P tolerance. [ABSTRACT FROM AUTHOR]

The effect of copper and nickel ions on the lipid composition of freshwater mussels Anodonta cygnea was investigated using an aquarium experiment. The contents of the main lipid classes were determined using thin layer chromatography and spectrophotometry, and the fatty acid composition was analysed using gas--liquid chromatography. The results indicated that copper and nickel had different effects on the mussels' lipid composition, with copper producing less effect on the composition of lipids and fatty acids than nickel. On the first experiment day, excessive copper content in the organism caused oxidative stress and modifications in membrane lipids, which returned to their initial level by the end of the experiment. Nickel accumulated predominantly in gills; however, significant modifications in lipids and fatty acids were seen also in the digestive gland from the first day of the experiment. This indicated the activation of nickel-induced lipid peroxidation processes. Moreover, this study revealed a dose-dependent effect of nickel on lipid composition, which was likely related to the development of compensatory biochemical mechanisms in response to nickel-induced oxidative stress. A comparative study of the lipid composition alteration in mussels in response to copper and nickel action revealed the consequences of the toxic impact of metal ions and the defensive mechanisms that organisms employ to detoxify and remove xenobiotics. [ABSTRACT FROM AUTHOR]

We conducted a lipidomic analysis of the whole body of female Aedes aegypti mosquitoes at different time points over the course of feeding and reproduction. There were temporal biphasic increases of more than 80% of lipids identified at the time of feeding and from 16 h to 30 h post blood meal (PBM). During these two increases, the abundance of many lipids dropped while body weight remained stable, probably reflecting blood lipid digestion and the synthesis of vitellogenin in this period. A concerted temporal pattern was particularly strong at the second peak for membrane and signalling lipids such as phosphatidylethanolamine (PE), phosphatidylinositol (PI), cardiolipin (CL), hexosylceramide (HexCer) and lyso-phosphatidic acid (LPA). Lyso-glycerophospholipids showed three distinct change patterns that are functionally related: Lyso-PE and Lyso-phosphatidylcholine (LPC), which are membrane lipids, showed little change; LPA, a signalling lipid, showed a significant increase from 16 to 30 h PBM; Lyso-PI, a bioactive lipid, and both lyso-phosphatidylglycerol (LPG) and lyso-phosphatidylserine (LPS), which are bacterial membrane lipids, showed one significant increase from the time of feeding to 16 h post blood meal. The result of our study on the anautogenous insect Ae. aegypti point to specific lipids likely to be important in the reproductive process with a role in the formation and growth of ovarian follicles. [ABSTRACT FROM AUTHOR]

Lipid membrane turnover and myelin repair play a central role in diseases and lesions of the central nervous system (CNS). The aim of the present study was to analyze lipid composition changes due to inflammatory conditions. We measured the fatty acid (FA) composition in erythrocytes (RBCs) and spinal cord tissue (gas chromatography) derived from mice affected by experimental allergic encephalomyelitis (EAE) in acute and remission phases; cholesterol membrane content (Filipin) and GM1 membrane assembly (CT-B) in EAE mouse RBCs, and in cultured neurons, oligodendroglial cells and macrophages exposed to inflammatory challenges. During the EAE acute phase, the RBC membrane showed a reduction in polyunsaturated FAs (PUFAs) and an increase in saturated FAs (SFAs) and the omega-6/omega-3 ratios, followed by a restoration to control levels in the remission phase in parallel with an increase in monounsaturated fatty acid residues. A decrease in PUFAs was also shown in the spinal cord. CT-B staining decreased and Filipin staining increased in RBCs during acute EAE, as well as in cultured macrophages, neurons and oligodendrocyte precursor cells exposed to inflammatory challenges. This regulation in lipid content suggests an increased cell membrane rigidity during the inflammatory phase of EAE and supports the investigation of peripheral cell membrane lipids as possible biomarkers for CNS lipid membrane concentration and assembly. [ABSTRACT FROM AUTHOR]

The characteristic shape changes observed in the growth and division of L-form cells have been explained by several theoretical studies and simulations using a vesicle model in which the membrane area increases with time. In those theoretical studies, characteristic shapes such as tubulation and budding were reproduced in a non-equilibrium state, but it was not possible to incorporate deformations that would change the topology of the membrane. We constructed a vesicle model in which the area of the membrane increases using coarse-grained particles and analyzed the changes in the shape of growing membrane by the dissipative particle dynamics (DPD) method. In the simulation, lipid molecules were added to the lipid membrane at regular time intervals to increase the surface area of the lipid membrane. As a result, it was found that the vesicle deformed into a tubular shape or a budding shape depending on the conditions for adding lipid molecules. This suggests that the difference in the place where new lipid molecules are incorporated into the cell membrane during the growth of L-form cells causes the difference in the transformation pathway of L-form cells. [ABSTRACT FROM AUTHOR]

Unilamellar vesicles of the biologically relevant lipids phosphatidic acid (PA) and phosphatidylserine (PS) with fully saturated (DM-) or partly unsaturated (PO-) acyl side chains were exposed to Ca, Mn and Mg in single metal additions; in equimolar mixtures or by sequential additions of one metal at a time. Laurdan generalized polarization measured the membrane fluidity, while dynamic light scattering reported liposome size changes complemented by zeta potential. All metals induced membrane rigidity and increased liposome sizes across all systems. Mn had the strongest effect overall, but Mg was comparable for DMPS. Lipid side chain architecture was important as GP values for binary mixtures were higher than expected from the sum of values for single additions added to POPS but smaller for DMPS. Sequential additions were predominantly different for Ca:Mg mixtures. Mn induced the strongest increase of liposome size in saturated lipids whereas Ca effects dominated unsaturated matrices. Binary additions induced larger sizes than the sum of single additions for POPS, but much lower changes in DMPA. The order of addition was relevant for PS systems. Thus, lipid structure determines metal effects, but their impact is modulated by other ions. Thus, metal effects may differ with the local lipid architecture and metal concentrations within cells. [ABSTRACT FROM AUTHOR]

Mycelial fungi grow as colonies consisting of polar growing hyphae, developing radially from spore or inoculum. Over time, the colony develops, hyphae are subject to various exogenous or endogenous stimuli, and mycelium becomes heterogeneous in growth, gene expression, biosynthesis, and secretion of proteins and metabolites. Although the biochemical and molecular mechanisms of mycelium heterogeneity have been the subject of many studies, the role of lipids in colony development and zonality is still not understood. This work was undertaken to extend our knowledge of mycelium heterogeneity and to answer the question of how different lipid molecular species are distributed in the surface colony of the basidial fungus Flammulina velutipes and how this distribution correlates with its morphology. The heterogeneity in the lipid metabolism and lipid composition of the fungal mycelium was demonstrated. According to the real-time PCR and LC-MS/MS results, the expression of genes of PC metabolism, accumulation of phospholipid classes, and degree of unsaturation of PC and PE increased in the direction from the center to the periphery of the colony. The peripheral zone of the colony was characterized by a higher value of the PC/PE ratio and a higher level of phospholipids esterified by linolenic acid. Considering that the synthesis of phospholipids in fungi occurs in different ways, we also conducted experiments with deuterium-labeled phospholipid precursors and found out that the Kennedy pathway is the predominant route for PC biosynthesis in F. velutipes. The zonal differences in gene expression and lipid composition can be explained by the participation of membrane lipids in polar growth maintenance and regulation. [ABSTRACT FROM AUTHOR]

Lipids that have two tails of different lengths are found throughout biomembranes in nature, yet the effects of this asymmetry on the membrane properties are not well understood, especially when it comes to the membrane dynamics. Here we study the nanoscale bending fluctuations in model mixed-chain 14:0–18:0 PC (MSPC) and 18:0–14:0 PC (SMPC) lipid bilayers using neutron spin echo (NSE) spectroscopy. We find that despite the partial interdigitation that is known to persist in the fluid phase of these membranes, the collective fluctuations are enhanced on timescales of tens of nanoseconds, and the chain-asymmetric lipid bilayers are softer than an analogous chain-symmetric lipid bilayer with the same average number of carbons in the acyl tails, di-16:0 PC (DPPC). Quantitative comparison of the NSE results suggests that the enhanced bending fluctuations at the nanosecond timescales are consistent with experimental and computational studies that showed the compressibility moduli of chain-asymmetric lipid membranes are 20% to 40% lower than chain-symmetric lipid membranes. These studies add to growing evidence that the partial interdigitation in mixed-chain lipid membranes is highly dynamic in the fluid phase and impacts membrane dynamic processes from the molecular to mesoscopic length scales without significantly changing the bilayer thickness or area per lipid. [ABSTRACT FROM AUTHOR]

Lipid metabolism is the major intracellular mechanism driving a variety of cellular functions such as energy storage, hormone regulation and cell division. Lipids, being a primary component of the cell membrane, play a pivotal role in the survival of macrophages. Lipids are crucial for a variety of macrophage functions including phagocytosis, energy balance and ageing. However, functions of lipids in macrophages vary based on the site the macrophages are residing at. Lipid-loaded macrophages have recently been emerging as a hallmark for several diseases. This review discusses the significance of lipids in adipose tissue macrophages, tumor-associated macrophages, microglia and peritoneal macrophages. Accumulation of macrophages with impaired lipid metabolism is often characteristically observed in several metabolic disorders. Stress signals differentially regulate lipid metabolism. While conditions such as hypoxia result in accumulation of lipids in macrophages, stress signals such as nutrient deprivation initiate lipolysis and clearance of lipids. Understanding the biology of lipid accumulation in macrophages requires the development of potentially active modulators of lipid metabolism. [ABSTRACT FROM AUTHOR]

Lipids are the fundamental components of cell membranes and they play a significant role in their integrity and fluidity. The alteration in lipid composition of membranes has been reported to be a major response to abiotic environmental stresses. Seasonal dynamics of membrane lipids in the shoots of Ephedra monosperma J.G. Gmel. ex C.A. Mey. growing in natural conditions of permafrost ecosystems was studied using HPTLC, GC-MS and ESI-MS. An important role of lipid metabolism was established during the autumn-winter period when the shoots of the evergreen shrub were exposed to low positive (3.6 °C), negative (−8.3 °C) and extremely low temperatures (−38.4 °C). Maximum accumulation of phosphatidic acid (PA), the amount of which is times times greater than the sum of phosphatidylcholine and phosphatidylethanolamine (PC + PE) was noted in shoots of E. monosperma in the summer-autumn period. The autumn hardening period (3.6 °C) is accompanied by active biosynthesis and accumulation of membrane lipids, a decrease of saturated 34:1 PCs, 34:1 PEs and 34:1 PAs, and an increase in unsaturated long-chain 38:5 PEs, 38:6 PEs, indicating that the adaptation of E. monosperma occurs not at the level of lipid classes but at the level of molecular species. At a further decrease of average daily air temperature in October (−8.3 °C) a sharp decline of PA level was registered. At an extreme reduction of environmental temperature (−38.4 °C) the content of non-bilayer PE and PA increases, the level of unsaturated fatty acids (FA) rises due to the increase of C18:2(Δ9,12) and C18:3(Δ9,12,15) acids and the decrease of C16:0 acids. It is concluded that changes in lipid metabolism reflect structural and functional reorganization of cell membranes and are an integral component of the complex process of plant hardening to low temperatures, which contributes to the survival of E. monosperma monocotyledonous plants in the extreme conditions of the Yakutia cryolithozone. [ABSTRACT FROM AUTHOR]

Lipid transporters synergistically contribute to oil accumulation under normal conditions in microalgae; however, their effects on lipid metabolism under stress conditions are unknown. Here, we examined the effect of the co-expression of lipid transporters, fatty acid transporters, (FAX1 and FAX2) and ABC transporter (ABCA2) on lipid metabolism and physiological changes in the green microalga Chlamydomonas under nitrogen (N) starvation. The results showed that the TAG content in FAX1-FAX2-ABCA2 over-expressor (OE) was 2.4-fold greater than in the parental line. Notably, in FAX1-FAX2-ABCA2-OE, the major membrane lipids and the starch and cellular biomass content also significantly increased compared with the control lines. Moreover, the expression levels of genes directly involved in TAG, fatty acid, and starch biosynthesis were upregulated. FAX1-FAX2-ABCA2-OE showed altered photosynthesis activity and increased ROS levels during nitrogen (N) deprivation. Our results indicated that FAX1-FAX2-ABCA2 overexpression not only enhanced cellular lipids but also improved starch and biomass contents under N starvation through modulation of lipid and starch metabolism and changes in photosynthesis activity. The strategy developed here could also be applied to other microalgae to produce FA-derived energy-rich and value-added compounds. [ABSTRACT FROM AUTHOR]

The authors suggest not only that sphingolipid metabolism may be an interesting therapeutic target for these diseases, but also that a diet controlling the specific affected sphingolipids might provide a beneficial effect to patients. Lipids are undoubtedly the major constituents of the cell membranes of all living organisms, and the most efficient source of energy [[1]]. Their ability to act as signaling mediators has earned them the name "bioactive lipids" [[2]]; said bioactive lipids are divided into four main families: classical eicosanoids, glycerophospholipids and sphingolipids, specialized pro-resolving lipid mediators, and endocannabinoids [[3]]. Interestingly, all the studies focused on restricted classes of lipids, and no papers proposed for this Special Issue primarily addressed the manifold bioactive lipids that signal both paracrinally and autocrinally by regulating key neuroinflammatory processes, which currently seem to represent one of the most regularly studied features that the different neurodegenerative diseases have in common. [Extracted from the article]

Usnic acid (UA), a unique lichen metabolite, is a protonophoric uncoupler of oxidative phosphorylation, widely known as a weight-loss dietary supplement. In contrast to conventional proton-shuttling mitochondrial uncouplers, UA was found to carry protons across lipid membranes via the induction of an electrogenic proton exchange for calcium or magnesium cations. Here, we evaluated the ability of various divalent metal cations to stimulate a proton transport through both planar and vesicular bilayer lipid membranes by measuring the transmembrane electrical current and fluorescence-detected pH gradient dissipation in pyranine-loaded liposomes, respectively. Thus, we obtained the following selectivity series of calcium, magnesium, zinc, manganese and copper cations: Zn2+ > Mn2+ > Mg2+ > Ca2+ >> Cu2+. Remarkably, Cu2+ appeared to suppress the UA-mediated proton transport in both lipid membrane systems. The data on the divalent metal cation/proton exchange were supported by circular dichroism spectroscopy of UA in the presence of the corresponding cations. [ABSTRACT FROM AUTHOR]

Since CVDs are often associated with lipid disorders, several research articles explored the possibility that the lipid metabolism can be affected in RA. Hepatic lipid metabolism deregulations are frequently associated with the development of nonalcoholic fatty liver disease (NFALD), a major health problem often leading to cirrhosis and hepatocellular carcinoma. Lipids are hydrophobic molecules involved in a plethora of biological functions; for example, they are employed for the storage of energy, serve as essential constituents of cell membranes and participate in the assembly of bilayer configuration. Lipid reprogramming is not a prerogative of colon cancer, since a number of other tumors, such as hepatocellular carcinoma, are characterized by a shift in the lipid metabolism. [Extracted from the article]

The ability of polymyxin B, an antibiotic used to treat infections caused by multidrug-resistant Gram-negative bacteria as a last-line therapeutic option, to form ion pores in model membranes composed of various phospholipids and lipopolysaccharides was studied. Our data demonstrate that polymyxin B predominantly interacts with negatively charged lipids. Susceptibility decreases as follows: Kdo2-Lipid A >> DOPG ≈ DOPS >> DPhPG ≈ TOCL ≈ Lipid A. The dimer and hexamer of polymyxin B are involved in the pore formation in DOPG(DOPS)- and Kdo2-Lipid A-enriched bilayers, respectively. The pore-forming ability of polymyxin B significantly depends on the shape of membrane lipids, which indicates that the antibiotic produces toroidal lipopeptide-lipid pores. Small amphiphilic molecules diminishing the membrane dipole potential and inducing positive curvature stress were shown to be agonists of pore formation by polymyxin B and might be used to develop innovative lipopeptide-based formulations. [ABSTRACT FROM AUTHOR]

Ceramides are a class of sphingolipids which are implicated in skin disorders, obesity, and other metabolic diseases. As a class with pleiotropic effects, recent efforts have centred on discerning specific ceramide species and their effects on atopic dermatitis, obesity, type 2 diabetes, and cardiovascular diseases. This delineation has allowed the identification of disease biomarkers, with long acyl chain ceramides such as C16- and C18-ceramides linked to metabolic dysfunction and cardiac function decline, while ultra-long acyl chain ceramides (>25 carbon acyl chain) were reported to be essential for maintaining a functional skin barrier. Given the intricate link between free fatty acids with ceramides, especially the de novo synthetic pathway, intracellular lipid droplet formation is increasingly viewed as an important mechanism for preventing accumulation of toxic ceramide species. Here, we review recent reports of various ceramide species involved in skin abnormalities and metabolic diseases, and we propose that promotion of lipid droplet biogenesis can be seen as a potential protective mechanism against deleterious ceramides. [ABSTRACT FROM AUTHOR]

Dissipative particle dynamics simulations were performed to investigate the self-assembly of dipalmitoylphosphatidylcholine (DPPC) as a model lipid membrane on the surface of carbon nanotubes (CNTs). The influence of surface curvature of CNTs on self-assembly was investigated by performing simulations on solutions of DPPC in water in contact with CNTs of different diameters: CNT (10, 10), CNT (14, 14), CNT (20, 20), and CNT (34, 34). DPPC solutions with a wide range of concentrations were chosen to allow for formation of lipid structures of various surface densities, ranging from a submonolayer to a well-organized monolayer and a CNT covered with a lipid monolayer immersed in a planar lipid bilayer. Our results are indicative of a sequence of phase-ordering processes for DPPC on the surface of CNTs. At low surface coverages, the majority of hydrocarbon tail groups of DPPC are in contact with the CNT surface. Increasing the surface coverage leads to the formation of hemimicellar aggregates, and at high surface coverages close to the saturation limit, an organized lipid monolayer self-assembles. An examination of the mechanism of self-assembly reveals a two-step mechanism. The first step involves densification of DPPC on the CNT surface. Here, the lipid molecules do not adopt the order of the target phase (lipid monolayer on the CNT surface). In the second step, when the lipid density on the CNT surface is above a threshold value (close to saturation), the lipid molecules reorient themselves to form an organized monolayer around the tube. Here, the DPPC molecules adopt stretched conformations normal to the surface, the end hydrocarbon groups adsorb on the surface, and the head groups occupy the outermost part of the monolayer. The saturation density and the degree of lipid ordering on the CNT surface depend on the surface curvature. The saturation density increases with increased surface curvature, and better-ordered structures are formed on less curved surfaces. [ABSTRACT FROM AUTHOR]

Molecular mechanisms behind obesity and sex-related effects in adipose tissue remain elusive. During adipocyte expansion, adipocytes undergo drastic remodelling of lipid membrane compositions. Lipid flippases catalyse phospholipid translocation from exoplasmic to the cytoplasmic leaflet of membranes. The present study aimed to analyse the effect of sex, obesity, and their interactions on the gene expression of two lipid flippases—ATP8A1 and ATP8B1—and their possible microRNA (miR) modulators in visceral adipose tissue (VAT). In total, 12 normal-weight subjects (5 premenopausal women and 7 men) and 13 morbidly obese patients (7 premenopausal women and 6 men) were submitted to surgery, and VAT samples were obtained. Gene expression levels of ATP8A1, ATP8B1, miR-548b-5p, and miR-4643 were measured in VAT. Our results showed a marked influence of obesity on VAT ATP8A1 and ATP8B1, although the effects of obesity were stronger in men for ATP8A1. Both genes positively correlated with obesity and metabolic markers. Furthermore, ATP8B1 was positively associated with miR-548b-5p and negatively associated with miR-4643. Both miRs were also affected by sex. Thus, lipid flippases are altered by obesity in VAT in a sex-specific manner. Our study provides a better understanding of the sex-specific molecular mechanisms underlying obesity, which may contribute to the development of sex-based precision medicine. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD), which is defined as a condition causing the gradual loss of kidney function, shows renal lipid droplet (LD) accumulation that is associated with oxidative damage. There is a possibility that an LD abnormality in quality plays a role in CKD development. This study aimed to explore the chemical composition of LDs that are induced in human kidney cells during exposure to free fatty acids as an LD source and oxidized lipoproteins as oxidative stress. The LDs were aspirated directly from cells using nanotips, followed by in-tip microextraction, and the LD lipidomic profiling was conducted using nanoelectrospray mass spectrometry. As a result, the free fatty acids increased the LD lipid content and, at the same time, changed their composition significantly. The oxidized lipoproteins caused distorted proportions of intact lipids, such as triacylglycerols (TG), phosphatidylcholines (PC), phosphatidylethanolamines (PE), and cholesteryl esters (CE). Notably, the oxidized lipids, including the hydroperoxides of TG, PC, and PE, exhibited significant elevations in dose-dependent manners. Furthermore, the dysregulation of intact lipids was paralleled with the accumulation of lipid hydroperoxides. The present study has revealed that the oxidation of lipids and the dysregulation of the lipid metabolism coexisted in LDs in the kidney cells, which has provided a potential new target for diagnosis and new insights into CKD. [ABSTRACT FROM AUTHOR]

Revealing the structures and dynamic behaviors of molecules on lipids is crucial for understanding the mechanism behind the biophysical processes, such as the preparation and application of drug delivery vesicles. Second harmonic generation (SHG) has been developed as a powerful tool to investigate the molecules on various lipid membranes, benefiting from its natural property of interface selectivity, which comes from the principle of even order nonlinear optics. Fluorescence emission, which is in principle not interface selective but varies with the chemical environment where the chromophores locate, can reveal the dynamics of molecules on lipids. In this contribution, we review some examples, which are mainly from our recent works focusing on the application of combined spectroscopic methods, i.e., SHG and two-photon fluorescence (TPF), in studying the dynamic behaviors of several dyes or drugs on lipids and surfactants. This review demonstrates that molecules with both SHG and TPF efficiencies may be used as intrinsic dual-probes in plotting a clear physical picture of their own behaviors, as well as the dynamics of other molecules, on lipid membranes. [ABSTRACT FROM AUTHOR]

Lipid assimilation, storage, and turnover impact growth, development, and virulence in many microbial pathogens including fungi. Perilipins are proteins associated with lipid droplets (LDs) that mediate their assembly and turnover. Here, we characterized the Beauveria bassiana (BbPlin1) perilipin. BbPlin1 expression was higher in minimal media than in rich media, and, using a BbPlin1::eGFP fusion protein, the protein was shown to be co–localized to LDs, with the high expression seen during infection and proliferation within the insect (Galleria mellonella) host that dramatically decreased to almost no expression during fungal outgrowth on cadavers including in conidia, but that BbPlin1 production resumed in the conidia once placed in nutrient–containing media allowing for germination and growth. Characterization of a targeted gene deletion strain (ΔBbPlin1) revealed a dramatic (>30%) reduction in cellular LD content, promotion of aerial hyphal growth, and a small decrease in virulence, with little to no effects on vegetative growth and stress responses. However, in the ΔBbPlin1 strain, expression of the complementary LD–associated caleosin gene, BbCal1, was enhanced under nutrient–poor conditions, although no changes in BbPlin1 expression were seen in a ΔBbCal1 strain and the expression of BbPlin1 in the ΔBbCal1 strain did not change LD patterns in cells. Transcriptome and RT–PCR analyses indicated increased expression of lipid metabolism–related genes, including triacylglyercol lipase 3, enoyl–CoA isomerase, and diacylglycerol–O–acetyl transferase in the BbPlin1 deletion mutant. Lipid profile analyses confirmed that the loss of BbPlin1 significantly reduced the cellular levels of contents of triacylglycerol, diacylglycerol, and phosphatidylethanolamine as compared to the wild–type strain. These results demonstrate the involvement of the B. bassiana perilipin in mediating lipid homeostasis, fungal aerial hyphal growth, and virulence, revealing critical cycling from high expression during nutrient utilization within host cadavers to low expression during growth on the surface of the cadaver during the infection process. [ABSTRACT FROM AUTHOR]

Melittin, the main toxic component in the venom of the European honeybee, interacts with natural and artificial membranes due to its amphiphilic properties. Rather than interacting with a specific receptor, melittin interacts with the lipid components, disrupting the lipid bilayer and inducing ion leakage and osmotic shock. This mechanism of action is shared with pneumolysin and other members of the cholesterol-dependent cytolysin family. In this manuscript, we investigated the inverse correlation for cholesterol dependency of these two toxins. While pneumolysin-induced damage is reduced by pretreatment with the cholesterol-depleting agent methyl-β-cyclodextrin, the toxicity of melittin, after cholesterol depletion, increased. A similar response was also observed after a short incubation with lipophilic simvastatin, which alters membrane lipid organization and structure, clustering lipid rafts. Therefore, changes in toxin sensitivity can be achieved in cells by depleting cholesterol or changing the lipid bilayer organization. [ABSTRACT FROM AUTHOR]

Guanine nucleotides can flip between a North and South conformation in the ribose moiety. To test the enzymatic activity of GTPases bound to nucleotides in the two conformations, we generated methanocarba guanine nucleotides in the North or South envelope conformations, i.e., (N)-GTP and (S)-GTP, respectively. With dynamin as a model system, we examined the effects of (N)-GTP and (S)-GTP on dynamin-mediated membrane constriction, an activity essential for endocytosis. Dynamin membrane constriction and fission activity are dependent on GTP binding and hydrolysis, but the effect of the conformational state of the GTP nucleotide on dynamin activity is not known. After reconstituting dynamin-mediated lipid tubulation and membrane constriction in vitro, we observed via cryo-electron microscopy (cryo-EM) that (N)-GTP, but not (S)-GTP, enables the constriction of dynamin-decorated lipid tubules. These findings suggest that the activity of dynamin is dependent on the conformational state of the GTP nucleotide. However, a survey of nucleotide ribose conformations associated with dynamin structures in nature shows almost exclusively the (S)-conformation. The explanation for this mismatch of (N) vs. (S) required for GTP analogues in a dynamin-mediated process will be addressed in future studies. [ABSTRACT FROM AUTHOR]