The non-enzymatic oxidation of phosphatidylethanolamine and phosphatidylserine and their intriguing roles in inflammation dynamics and diseases.

Phosphatidylethanolamine (PE) and phosphatidylserine (PS), along with phosphatidylcholine (PC), are key phospholipids (PL) in cell membranes and lipoproteins, prone to oxidative modifications. Their oxidized forms, OxPE and OxPS, play significant roles in inflammation and immune response. This review explores their structural oxidative changes under non-enzymatic conditions and their roles in physiological and pathological contexts, influencing inflammation, and immunity. Specific oxidations of PE and PS significantly alter their physicochemical properties, leading to enhanced biological functions, reduced activity, or inactivation. OxPE may show pro-inflammatory actions, similar to well-documented OxPC, while the OxPS pro-inflammatory effects are less noted. However, OxPS and OxPE have also shown an antagonistic effect against lipopolysaccharides (LPS), suggesting a protective role against exacerbated immune responses, similar to OxPC. Further research is needed to deepen our understanding of these less-studied OxPL classes. The role of OxPE and OxPS in disease pathogenesis remains largely unexplored, with limited studies linking them to Alzheimer's disease, diabetes, rheumatoid arthritis, traumatic brain injury, and skin inflammation. These findings highlight the potential of OxPE and OxPS as biomarkers for disease diagnosis, monitoring, and therapeutic targeting.

Plant and algal lipidomes: Analysis, composition, and their societal significance.

Plants and algae play a crucial role in the earth's ecosystems. Through photosynthesis they convert light energy into chemical energy, capture CO2 and produce oxygen and energy-rich organic compounds. Photosynthetic organisms are primary producers and synthesize the essential omega 3 and omega 6 fatty acids. They have also unique and highly diverse complex lipids, such as glycolipids, phospholipids, triglycerides, sphingolipids and phytosterols, with nutritional and health benefits. Plant and algal lipids are useful in food, feed, nutraceutical, cosmeceutical and pharmaceutical industries but also for green chemistry and bioenergy. The analysis of plant and algal lipidomes represents a significant challenge due to the intricate and diverse nature of their composition, as well as their plasticity under changing environmental conditions. Optimization of analytical tools is crucial for an in-depth exploration of the lipidome of plants and algae. This review highlights how lipidomics analytical tools can be used to establish a complete mapping of plant and algal lipidomes. Acquiring this knowledge will pave the way for the use of plants and algae as sources of tailored lipids for both industrial and environmental applications. This aligns with the main challenges for society, upholding the natural resources of our planet and respecting their limits.

The green seaweed Ulva: tomorrow's "wheat of the sea" in foods, feeds, nutrition, and biomaterials.

Ulva, a genus of green macroalgae commonly known as sea lettuce, has long been recognized for its nutritional benefits for food and feed. As the demand for sustainable food and feed sources continues to grow, so does the interest in alternative, plant-based protein sources. With its abundance along coastal waters and high protein content, Ulva spp. have emerged as promising candidates. While the use of Ulva in food and feed has its challenges, the utilization of Ulva in other industries, including in biomaterials, biostimulants, and biorefineries, has been growing. This review aims to provide a comprehensive overview of the current status, challenges and opportunities associated with using Ulva in food, feed, and beyond. Drawing on the expertise of leading researchers and industry professionals, it explores the latest knowledge on Ulva's nutritional value, processing methods, and potential benefits for human nutrition, aquaculture feeds, terrestrial feeds, biomaterials, biostimulants and biorefineries. In addition, it examines the economic feasibility of incorporating Ulva into aquafeed. Through its comprehensive and insightful analysis, including a critical review of the challenges and future research needs, this review will be a valuable resource for anyone interested in sustainable aquaculture and Ulva's role in food, feed, biomaterials, biostimulants and beyond.

Tracing the Impact of Domestic Storage Conditions on Antioxidant Activity and Lipid Profiles in the Edible Microalgae Chlorella vulgaris and Tetraselmis chui.

The microalgae Chlorella vulgaris and Tetraselmis chui are valued for their nutrient-rich content, including lipids and polyunsaturated fatty acids (PUFA). However, little is known about how storage and processing affect their lipid quality. This study aimed to assess the impact of domestic storage and cooking practices in dried biomass of C. vulgaris and T. chui. Four conditions were tested: control (newly opened package), light (storage at room temperature and daily light regimen for three weeks), frozen (storage in the freezer at -20 °C for three weeks), and heated (three cycles of 90 min at 100 °C). Lipid extracts were analyzed by GC-MS and LC-MS, and antioxidant activity through DPPH and ABTS radical scavenging assays. Tested storage conditions promoted a decrease in fatty acid content and in diacyl/lyso lipid species ratios of phospholipid (PC/LPC, PE/LPE) and betaine lipids (DGTS/MGTS). Lipid extracts from light treatment showed the lowest antioxidant activity in C. vulgaris (ABTS, IC40: 104.9; DPPH, IC20: 187.9 ± 15.0), while heat affected the antioxidant activity of T. chui (ABTS, IC40: 88.5 ± 2.8; DPPH, IC20 209.4 ± 10.9). These findings underscore the impact of managing storage and processing conditions to optimize the nutritional and functional benefits of C. vulgaris and T. chui in food and feed applications.

Mitochondrial Metabolism Drives Low-density Lipoprotein-induced Breast Cancer Cell Migration.

Most cancer-related deaths are due to metastases. Systemic factors, such as lipid-enriched environments [as low-density lipoprotein (LDL)-cholesterol], favor breast cancer, including triple-negative breast cancer (TNBC) metastasis formation. Mitochondria metabolism impacts TNBC invasive behavior but its involvement in a lipid-enriched setting is undisclosed. Here we show that LDL increases lipid droplets, induces CD36 and augments TNBC cells migration and invasion in vivo and in vitro. LDL induces higher mitochondrial mass and network spread in migrating cells, in an actin remodeling-dependent manner, and transcriptomic and energetic analyses revealed that LDL renders TNBC cells dependent on fatty acids (FA) usage for mitochondrial respiration. Indeed, engagement on FA transport into the mitochondria is required for LDL-induced migration and mitochondrial remodeling. Mechanistically, LDL treatment leads to mitochondrial long-chain fatty acid accumulation and increased reactive oxygen species (ROS) production. Importantly, CD36 or ROS blockade abolished LDL-induced cell migration and mitochondria metabolic adaptations. Our data suggest that LDL induces TNBC cells migration by reprogramming mitochondrial metabolism, revealing a new vulnerability in metastatic breast cancer. Significance: LDL induces breast cancer cell migration that relies on CD36 for mitochondrial metabolism and network remodeling, providing an antimetastatic metabolic strategy.

Bioprospecting Bioactive Polar Lipids from Olive (Olea europaea cv. Galega vulgar) Fruit Seeds: LC-HR-MS/MS Fingerprinting and Sub-Geographic Comparison.

Olive seeds have been considered as a new nutritionally healthy food supplement. They are rich in monounsaturated n-9 and essential polyunsaturated n-6 lipids. However, little is known about their polar lipids, potentially bioactive and chemical identity markers for olive pulp and oil. This work aimed to identify the polar lipidome of olive seeds to find possible bioactive compounds and markers of geographic origin, by studying samples from six Portuguese sub-regions. Polar lipids were obtained by solid/liquid extraction, NH2-solid-phase extraction, and identified by hydrophilic interaction liquid chromatography (HILIC)-HR-ESI-MS and MS/MS. Ninety-four compounds were identified, including phospholipids, glycolipids, sphingolipids, and acyl sterol glycosides, several of which bear polyunsaturated fatty acids. Multivariate statistical analysis found unique profiles within each sub-region and markers of geographic identity, primarily phosphatidylcholines, phosphatidylethanolamines, and lysophosphatidylethanolamines. Therefore, polar lipid signatures should be further investigated, to assess their bioactivity, nutritional value, and chemical identity for valuing olive seeds and their oil.

Multi-Omic Profiling of Macrophages Treated with Phospholipids Containing Omega-3 and Omega-6 Fatty Acids Reveals Complex Immunomodulatory Adaptations at Protein, Lipid and Metabolic Levels.

In recent years, several studies have demonstrated that polyunsaturated fatty acids have strong immunomodulatory properties, altering several functions of macrophages. In the present work, we sought to provide a multi-omic approach combining the analysis of the lipidome, the proteome, and the metabolome of RAW 264.7 macrophages supplemented with phospholipids containing omega-3 (PC 18:0/22:6; ω3-PC) or omega-6 (PC 18:0/20:4; ω6-PC) fatty acids, alone and in the presence of lipopolysaccharide (LPS). Supplementation of macrophages with ω3 and ω6 phospholipids plus LPS produced a significant reprogramming of the proteome of macrophages and amplified the immune response; it also promoted the expression of anti-inflammatory proteins (e.g., pleckstrin). Supplementation with the ω3-PC and ω6-PC induced significant changes in the lipidome, with a marked increase in lipid species linked to the inflammatory response, attributed to several pro-inflammatory signalling pathways (e.g., LPCs) but also to the pro-resolving effect of inflammation (e.g., PIs). Finally, the metabolomic analysis demonstrated that supplementation with ω3-PC and ω6-PC induced the expression of several metabolites with a pronounced inflammatory and anti-inflammatory effect (e.g., succinate). Overall, our data show that supplementation of macrophages with ω3-PC and ω6-PC effectively modulates the lipidome, proteome, and metabolome of these immune cells, affecting several metabolic pathways involved in the immune response that are triggered by inflammation.

Food grade extraction of Chlorella vulgaris polar lipids: A comparative lipidomic study.

Glycolipids and phospholipids are the main reservoirs of omega polyunsaturated fatty acids in microalgae. Their extraction for the food industry requires food grade solvents, however, the use of these solvents is generally associated with low extraction yields. In this study, we evaluated the lipid extraction efficiency of food-grade ethanol, ultrasound-assisted ethanol (UAE) and dichloromethane/methanol (DCM) from Chlorella vulgaris cultivated under autotrophic and heterotrophic conditions. Yields of lipids, fatty acids (FA), and complex lipid profiles were determined by gravimetry, GC-MS, and LC-MS/MS, respectively. UAE and DCM showed the highest lipid yields with similar purity. The FA profiles were identical for all extracts. The polar lipidome of the DCM and UAE extracts was comparable, while the EtOH extracts were significantly different. These results demonstrated the effectiveness of UAE extraction to obtain high yields of polar lipids and omega-3 and -6-rich extracts from C. vulgaris that can be used for food applications.

Photosynthesis from stolen chloroplasts can support sea slug reproductive fitness.

Some sea slugs are able to steal functional chloroplasts (kleptoplasts) from their algal food sources, but the role and relevance of photosynthesis to the animal host remain controversial. While some researchers claim that kleptoplasts are slowly digestible 'snacks', others advocate that they enhance the overall fitness of sea slugs much more profoundly. Our analysis shows light-dependent incorporation of 13C and 15N in the albumen gland and gonadal follicles of the sea slug Elysia timida, representing translocation of photosynthates to kleptoplast-free reproductive organs. Long-chain polyunsaturated fatty acids with reported roles in reproduction were produced in the sea slug cells using labelled precursors translocated from the kleptoplasts. Finally, we report reduced fecundity of E. timida by limiting kleptoplast photosynthesis. The present study indicates that photosynthesis enhances the reproductive fitness of kleptoplast-bearing sea slugs, confirming the biological relevance of this remarkable association between a metazoan and an algal-derived organelle.

Redox lipid reprogramming commands susceptibility of macrophages and microglia to ferroptotic death.

Ferroptotic death is the penalty for losing control over three processes-iron metabolism, lipid peroxidation and thiol regulation-that are common in the pro-inflammatory environment where professional phagocytes fulfill their functions and yet survive. We hypothesized that redox reprogramming of 15-lipoxygenase (15-LOX) during the generation of pro-ferroptotic signal 15-hydroperoxy-eicosa-tetra-enoyl-phosphatidylethanolamine (15-HpETE-PE) modulates ferroptotic endurance. Here, we have discovered that inducible nitric oxide synthase (iNOS)/NO•-enrichment of activated M1 (but not alternatively activated M2) macrophages/microglia modulates susceptibility to ferroptosis. Genetic or pharmacologic depletion/inactivation of iNOS confers sensitivity on M1 cells, whereas NO• donors empower resistance of M2 cells to ferroptosis. In vivo, M1 phagocytes, in comparison to M2 phagocytes, exert higher resistance to pharmacologically induced ferroptosis. This resistance is diminished in iNOS-deficient cells in the pro-inflammatory conditions of brain trauma or the tumour microenvironment. The nitroxygenation of eicosatetraenoyl (ETE)-PE intermediates and oxidatively truncated species by NO• donors and/or suppression of NO• production by iNOS inhibitors represent a novel redox mechanism of regulation of ferroptosis in pro-inflammatory conditions.