Abundant Lipid Research Articles

Study of Different Parameters Affecting Production and Productivity of Polyunsaturated Fatty Acids (PUFAs) and γ-Linolenic Acid (GLA) by Cunninghamella elegans Through Glycerol Conversion in Shake Flasks and Bioreactors.

Microbial cultures repurposing organic industrial residues for value-added metabolite production is pivotal for sustainable resource use. Highlighting polyunsaturated fatty acids (PUFAs), particularly gamma-linolenic acid (GLA), renowned for their nutritional and therapeutic value. Notably, Zygomycetes' filamentous fungi harbor abundant GLA-rich lipid content, furthering their relevance in this approach. In this study, the strain C. elegans NRRL Y-1392 was evaluated for its capability to metabolize glycerol and produce lipids rich in GLA under different culture conditions. Various carbon-to-nitrogen ratios (C/N = 11.0, 110.0, and 220.0 mol/mol) were tested in batch-flask cultivations. The highest GLA production of 224.0 mg/L (productivity equal to 2.0 mg/L/h) was observed under nitrogen excess conditions, while low nitrogen content promoted lipid accumulation (0.59 g of lipids per g of dry biomass) without yielding more PUFAs and GLA. After improving the C/N ratio at 18.3 mol/mol, even higher PUFA (600 mg/L) and GLA (243 mg/L) production values were recorded. GLA content increased when the fungus was cultivated at 12 °C (15.5% w/w compared to 12.8% w/w at 28 °C), but productivity values decreased significantly due to prolonged cultivation duration. An attempt to improve productivity by increasing the initial spore population did not yield the expected results. The successful scale-up of fungal cultivations is evidenced by achieving consistent results (compared to flask experiments under corresponding conditions) in both laboratory-scale (Working Volume-Vw = 1.8 L; C/N = 18.3 mol/mol) and semi-pilot-scale (Vw = 15.0 L; C/N = 110.0 mol/mol) bioreactor experiments. To the best of our knowledge, cultivation of the fungus Cunninghamella elegans in glycerol-based substrates, especially in 20 L bioreactor experiments, has never been previously reported in the international literature. The successful scale-up of the process in a semi-pilot-scale bioreactor illustrates the potential for industrializing the bioprocess.

Multi-omics analysis of chemical composition variation among different muscle types in Hu lamb.

Consumers' preferences for lamb meat vary greatly depending on the specific cut. Variations in the chemical composition across different muscle types play a crucial role in determining meat quality, particularly with regard to flavor. Therefore, it is essential to study the variations in chemical composition among different muscle types in lamb, as well as the mechanisms behind their formation, aiming to understand the flavor variation across the muscle types. Flank muscles showed significantly higher intramuscular fat content and muscle fiber diameter compared to triceps brachii and biceps femoris (BF), at the same time as displaying a significantly lower percentage of type I muscle fibers. Forty-three differentially abundant volatile compounds (DAVC) were identified across five muscles, with the majority of DAVCs being more abundant in the BF. In total, 161 differentially abundant lipids were identified across five muscles, with triglycerides (TG), phosphatidylcholines (PC), phosphatidyl ethanolamines (PE) and phosphatidylmethanol (PMeOH) showing a strong correlation with DAVCs. A lipid-gene regulatory network was established, encompassing 664 lipids and 11 107 genes, leading to the identification of pathways and genes that regulate the metabolism of PEs, PMeOH, PCs and TGs. The present study showed the significant variation in flavor compounds among the five edible muscles, as well as the potential reasons for their formation. The results potentially provide a theoretical foundation for improving the meat quality of lamb. © 2024 Society of Chemical Industry. Published by John Wiley & Sons Ltd.

Monogalactosyldiacylglycerol synthase isoforms play diverse roles inside and outside the diatom plastid.

Diatoms derive from a secondary endosymbiosis event, which occurred when a eukaryotic host cell engulfed a red alga. This led to the formation of a complex plastid enclosed by four membranes: two innermost membranes originating from the red alga chloroplast envelope, and two additional peri- and epiplastidial membranes (PPM, EpM). The EpM is linked to the endoplasmic reticulum (ER). The most abundant membrane lipid in diatoms is monogalactosyldiacylglycerol (MGDG), synthesized by galactosyltransferases called MGDG synthases (MGDs), conserved in photosynthetic eukaryotes and considered to be specific to chloroplast membranes. Similar to angiosperms, a multigenic family of MGDs has evolved in diatoms, but through an independent process. We characterized MGDα, MGDβ and MGDγ in Phaeodactylum tricornutum, combining molecular analyses, heterologous expression in Saccharomyces cerevisiae, and studying overexpressing and CRISPR-Cas9-edited lines. MGDα localizes mainly to thylakoids, MGDβ to the PPM, and MGDγ to the ER and EpM. MGDs have distinct specificities for diacylglycerol, consistent with their localization. Results suggest that MGDα is required for thylakoid expansion under optimal conditions, while MGDβ and MGDγ play roles in plastid and non-plastid membranes and in response to environmental stress. Functional compensation among MGDs likely contributes to diatom resilience under adverse conditions and to their ecological success.

SHARD: an improved method for staining and visualizing multiplex immunofluorescence in optically cleared postmortem human brain tissue.

Postmortem human brain tissue is a critical resource for studying neurodegenerative disease, providing critical insights into cellular morphology, pathology, and network connectivity. To improve standard microscopy and enable high-resolution, three-dimensional (3D) images of tissues at the subcellular level, tissue-clearing methods have been developed. These 3D images allow for the analysis of large regions of interest and can be used to study structural and spatial changes that occur during neurodegeneration. Additionally, 3D imaging facilitates the visualization of whole-cell morphology, especially in cells with long processes that would otherwise be truncated in single-plane images. Human brain tissue is especially challenging for tissue clearing due to the abundance of lipids in myelin and the need for optimal fixation and low postmortem intervals. Formaldehyde-based fixatives, commonly used in preserving tissue, hinder antibody binding by crosslinking important antibody epitopes, and fluorescent microscopy requires the incorporation of fluorescent labels through passive diffusion or electrophoresis. Recent studies have focused on optimally fixed human brain tissue with short postmortem intervals, limiting the general applicability of these methods. To address these challenges, we developed SHARD (SHIELD, antigen retrieval, and delipidation), a simple and widely applicable method for clearing and labeling human brain tissue, which can be applied to long-term banked human brain tissue preserved in formaldehyde. SHARD is a novel addition to the SHIELD tissue clarification method, combining antigen retrieval, tissue clearing, and staining of 200-μm sections from long-term banked human brain tissue. The SHARD method is effective for postmortem intervals (PMIs) ranging from 10 to 72 h in multiple neurodegenerative diseases and control samples. In this study, we demonstrate that the SHARD method significantly enhances the immunostaining of glial fibrillary acidic protein (GFAP), an astrocytic cytoskeletal marker. Overall, the combination of antigen retrieval and tissue delipidation holds great potential for achieving detailed 3D immunostaining in long-term formaldehyde-fixed postmortem human brain tissue, opening new avenues for research and discovery.

Metagenomic, metabolomic, and lipidomic shifts associated with fecal microbiota transplantation for recurrent Clostridioides difficile infection.

Recurrent C. difficile infection (rCDI) is an urgent public health threat, for which the last resort and lifesaving treatment is a fecal microbiota transplant (FMT). However, the exact mechanisms that mediate a successful FMT are not well-understood. Here, we use longitudinal stool samples collected from patients undergoing FMT to evaluate intra-individual changes in the microbiome, metabolome, and lipidome after successful FMTs relative to their baselines pre-FMT. We show changes in the abundance of many lipids, specifically a decrease in acylcarnitines post-FMT, and a shift from conjugated bile acids pre-FMT to deconjugated secondary bile acids post-FMT. These changes correlate with a decrease in Enterobacteriaceae, which encode carnitine metabolism genes, and an increase in Lachnospiraceae, which encode bile acid altering genes such as bile salt hydrolases (BSHs) and the bile acid-inducible (bai) operon, post-FMT. We also show changes in gut microbe-encoded amino acid biosynthesis genes, of which Enterobacteriaceae was the primary contributor to amino acids C. difficile is auxotrophic for. Liquid chromatography, ion mobility spectrometry, and mass spectrometry (LC-IMS-MS) revealed a shift from microbial conjugation of primary bile acids pre-FMT to secondary bile acids post-FMT. Here, we define the structural and functional changes associated with a successful FMT and generate hypotheses that require further experimental validation. This information is meant to help guide the development of new microbiota-focused therapeutics to treat rCDI.IMPORTANCERecurrent C. difficile infection is an urgent public health threat, for which the last resort and lifesaving treatment is a fecal microbiota transplant. However, the exact mechanisms that mediate a successful FMT are not well-understood. Here, we show changes in the abundance of many lipids, specifically acylcarnitines and bile acids, in response to FMT. These changes correlate with Enterobacteriaceae pre-FMT, which encodes carnitine metabolism genes, and Lachnospiraceae post-FMT, which encodes bile salt hydrolases and baiA genes. There was also a shift from microbial conjugation of primary bile acids pre-FMT to secondary bile acids post-FMT. Here, we define the structural and functional changes associated with a successful FMT, which we hope will help aid in the development of new microbiota-focused therapeutics to treat rCDI.

Differential Mobility Spectrometry-Based Cardiolipin Analysis.

Cardiolipins (CL) are special lipids in many respects. First of all, CL are composed of four fatty acids linked by two phosphatidic acids, which provide CL a unique molecular structure. Secondly, in eukaryotic cells they are specific to a single organelle, mitochondria, where they are also synthetized. CL are one of the most abundant lipid classes in mitochondria, mainly localized in the inner membrane. They are key determinants of mitochondrial health and homeostasis by modulating membrane integrity and fluidity, mitochondrial shapes, and metabolic pathways. Disturbances in mitochondrial CL composition can lead to tissue malfunction and diseases. It is therefore important to develop analytical tools to study the mitochondrial lipidome, and more particularly the CL. The method described here allows the quantification of cardiolipins at the sum composition level in isolated mitochondria or in liver tissue by flow injection analysis coupled to differential mobility spectrometry (FIA-DMS), also known as DMS-based shotgun lipidomics.

Unexpected asymmetric distribution of cholesterol and phospholipids in equilibrium model membranes

Lipid compositional asymmetry across the leaflets of the plasma membrane is a ubiquitous feature in eukaryotic cells. How this asymmetry is maintained is thought to be primarily controlled by active transport of lipids between leaflets. This strategy is facilitated by the fact that long tail phospholipids and sphingolipids diffuse through the lipid bilayer slowly – taking many hours or days. However, a lipid like cholesterol – which is the most abundant lipid in the plasma membrane of animal cells – has been harder to pin-point in terms of its favored side. In the present work we show that when a saturated lipid is added to a mix of the unsaturated lipid palmitoyl-oleoyl-phosphatidylcholine (POPC) and cholesterol, both cholesterol and the long tail phospholipids organize asymmetrically across the membrane’s leaflets naturally. In these extruded unilamellar vesicles, most cholesterol as well as the saturated lipid – dipalmitoylphosphatidylcholine (DPPC) or sphingomyelin (SM) – segregated to the inner leaflet while POPC preferentially localized in the outer leaflet. This asymmetric arrangement generated a slight phospholipid number imbalance favoring the outer leaflet and thus opposite to where cholesterol and the saturated lipids preferentially partitioned. These results were obtained using Magic Angle Spinning (MAS) NMR in combination with Small Angle Neutron Scattering (SANS) using isotope labeling to differentiate lipid species. We suggest that sidedness in membranes can be driven by thermodynamic processes. In addition, our MAS NMR results show that the lower bound for cholesterol’s flip-flop half-time at 45°C is 10ms, which is at least two orders of magnitude slower than current MD simulations predict. This result stands in stark contrast to previous work that suggested that cholesterol’s flip-flop half-time at 37°C has an upper bound of 10ms.

Effects of the organochlorine pesticide metabolite p,p’-DDE on the gastrointestinal lipidome in fish: A novel toxicity pathway for a legacy pollutant

Though phased out from use in the United States, environmental contamination by organochlorine pesticides (OCPs) remains a widespread issue, especially around intensive agricultural regions. OCPs, such as dichlorodiphenyltrichloroethane (DDT) and its primary metabolite, dichlorodiphenyldichloroethylene (DDE), have been detected in soils, sediments, surface waters, and biota decades after their discontinued use. As OCPs are persistent and can bioaccumulate in fats, these compounds can transfer and magnify across food webs. Freshwater predatory fish and birds can accumulate high OCP concentrations, leading to a myriad of deleterious impacts on organismal health. Studies have found evidence of reproductive disruption in predatory fish, such as the largemouth bass (LMB; Micropterus salmoides), associated with DDT and DDE exposure. DDE can act through estrogenic pathways and induce the expression of estrogenic signals in male animals; however, the molecular mechanism of disruption is unclear. Recently, metabolomics research has revealed corollary relationships between lipid signals and organic pollutant toxicity. Here, a two-month feeding experiment on LMB was conducted to assess the interactions of DDE (as p,p'-DDE) in food with gut and liver lipid signaling. Targeted lipidomic analysis revealed global alterations in the abundance of tissue lipids, especially cholesteryl esters and phospholipids, in LMB exposed to low levels of p,p'-DDE. Results from these studies indicate that p,p'-DDE may act through disruption of normal lipid homeostasis to cause toxicity in freshwater fish.

Constraining the sources of archaeal tetraether lipids in multiple cold seep provinces of the Cascadia Margin

Archaeal isoprenoid glycerol dialkyl glycerol tetraether lipid (iGDGT) abundance profiles and carbon isotopic compositions reflect the relative distributions of archaeal sources, including planktonic, benthic, and methane-cycling contributions. Here, we analyze the carbon isotope ratios of iGDGTs purified from sediments of three different cold seep sites in Cascadia Margin, off the coast of Washington, USA. Together with relative abundance and glycerol configurations, we use the carbon isotope ratios to estimate the contributions of multiple archaeal sources to the sedimentary iGDGT assemblages and their impact on values of the TEX86 and methane indices. Using a Bayesian mixing model, we robustly characterize three potential endmembers by determining their characteristic lipid distributions, inferred contributions to the total sediment inventory, and carbon isotopic signatures. Despite the geographic proximity of the sample locations, we find site-specific heterogeneity in relative iGDGT abundances and δ13C values. Planktonic and benthic methane-cycling sources predominate in all cases (contributing > 98 % of iGDGTs), while benthic non-methane cycling archaea contribute minimally to the sedimentary lipid pool. Environments with higher methane influence show an increased presence of anti-parallel iGDGTs, indicating that methane-cycling archaea may dominantly or exclusively synthesize iGDGTs in this configuration. Our results quantify the relationship between the methane index (MI) and methane impact in systems dominated by planktonic and benthic methane-cycling archaea. Within the framework of the TEX86 temperature proxy, this permits a quantitative demonstration that it is overly simplistic to apply a MI cutoff threshold as a binary indicator to determine methane influence, and caution is needed when taking this approach in paleoclimate reconstructions.

Raft-like lipid mixtures in the highly coarse-grained Cooke membrane model.

Lipid rafts are nanoscopic assemblies of sphingolipids, cholesterol, and specific membrane proteins. They are believed to underlie the experimentally observed lateral heterogeneity of eukaryotic plasma membranes and implicated in many cellular processes, such as signaling and trafficking. Ternary model membranes consisting of saturated lipids, unsaturated lipids, and cholesterol are common proxies because they exhibit phase coexistence between a liquid-ordered (lo) and liquid-disordered (ld) phase and an associated critical point. However, plasma membranes are also asymmetric in terms of lipid type, lipid abundance, leaflet tension, and corresponding cholesterol distribution, suggesting that rafts cannot be examined separately from questions about elasticity, curvature torques, and internal mechanical stresses. Unfortunately, it is challenging to capture this wide range of physical phenomenology in a single model that can access sufficiently long length- and time scales. Here we extend the highly coarse-grained Cooke model for lipids, which has been extensively characterized on the curvature-elastic front, to also represent raft-like lo/ld mixing thermodynamics. In particular, we capture the shape and tie lines of a coexistence region that narrows upon cholesterol addition, terminates at a critical point, and has coexisting phases that reflect key differences in membrane order and lipid packing. We furthermore examine elasticity and lipid diffusion for both phase separated and pure systems and how they change upon the addition of cholesterol. We anticipate that this model will enable significant insight into lo/ld phase separation and the associated question of lipid rafts for membranes that have compositionally distinct leaflets that are likely under differential stress-like the plasma membrane.

Responses of soil microbial metabolism, function and soil quality to long-term addition of organic materials with different carbon sources

Biochar and green manure have been widely applied in agricultural production and are important means to achieve sustainable agriculture. However, there is limited research systematically and comprehensively exploring the response of soil microbiota and the changes in soil metabolomics after the addition of two different carbon source amendments to the soil, and the differential mechanisms of soil metabolomics between them remain unclear. In this study, a long-term field experiment (initiated in 2019) was conducted to investigate the effects of biochar and green manure application on soil nutrients and soil functions driven by soil microbes. Compared to the pure fertilizer treatment, biochar increased soil total carbon by 14.54% to 27.04% and soil available potassium by 4.67% to 27.46%. Ryegrass significantly increased soil available phosphorus and organic matter. Under different fertilization regimes, the ecological niches of soil microbes changed significantly. Network analysis revealed that long-term ryegrass returning reduced the complexity of soil microbial networks. Ryegrass and biochar increased dispersal limitation in fungal assemblages (reaching 93.33% and 86.67%, respectively), with biochar particularly enhancing variable selection in bacterial assemblages (accounting for 53.33%). Variation partitioning analysis based on redundancy analysis indicated that humic substances had the highest explanatory power for microbial community variation, with humic substances explaining 38.49% of bacteria and 52.19% of fungi variation. The ryegrass treatment mainly changed the abundance of carbohydrates (CH), amines (AM), c (AH), and lipids (LP), while the BC treatment mainly altered the abundance of organic acids (AC), amines (AM), and carbohydrates (CH). Meanwhile, both treatments significantly reduced the bisphenol A, one of the soil pollutants. Ryegrass incorporation significantly increased the abundance of genes related to soil C, N, P, and S cycling, especially genes involved in carbon decomposition, while biochar significantly enhanced the abundance of nitrogen fixation genes nifH and Hao in soil. Random forest model results indicated that carbohydrates, alcohols, aromatics (AR), and ester (ES) were the main categories of metabolites in soil influenced by differential microbes, and Finegoldia served as a common important metabolic driving species. In summary, this study reveals the processes of soil function, microbial community succession, and metabolism driven by ryegrass and biochar, providing important insights for optimizing soil management and improving soil quality.Graphical

Effect of seven baking lipases on the lipid class composition of three different cakes

AbstractLipases are effective clean-label improvers for the baking quality of cake. Insights into lipase activities in different cake formulations in combination with the effect on batter/dough and baking quality are needed to further reveal the underlying mechanisms. Therefore, a method using normal phase high-performance liquid chromatography coupled to an evaporative light scattering detector was adapted and validated for the five most abundant lipid classes in three common cake recipes, namely triacylglycerols, diacylglycerols, monoacylglycerols, glycerophosphocholine and lysoglycerophosphocholine. The method revealed total changes of 0.2 mg/g to 186.5 mg/g in lipid class content per dry weight after lipase treatments. Comparative investigations on batter/dough and products of basic cake, pound cake and brioche without or with addition of seven lipases showed that the substrate specificity of lipases is the decisive factor for their effectiveness regarding improved dough and product quality. A high lipase activity only supported already matching substrate specificities. Graphical abstract

PSLBI-11 Relevance of mitochondrial-mediated apoptotic processes in color and oxidative stabilities of five different beef muscles

Abstract Fresh meat color stands as one of the most critical quality indicators influencing consumer perception of meat freshness and purchase decision. Variation in color and color stability among different muscle types exists due to differences in chemical compositions, including lipids and metabolites, and other redox stability-related biochemical properties. Understanding biochemical mechanisms governing color stability in different muscles will offer insights for the industry to develop practical strategies aimed at reducing food waste attributed to discoloration. The objective of the current study was to identify metabolites and lipid compounds potentially linked to oxidative stabilities and relevant biochemical properties across different bovine muscles. Five different muscles [longissimus lumborum (LL), gluteus medius (GM), biceps femoris (BF), semitendinosus (ST), and infraspinatus (IF)] were collected from 16 beef carcasses (USDA Choice) at 2-d postmortem. Multiple cuts were made from each muscle for meat color measurements including instrumental and sensory color evaluations during display, and biochemical attributes, including total reducing activity (TRA), mitochondria-swelling, mitochondrial-lipid oxidation, cytochrome c redox ability (CytC). For the lipidome and metabolome analyses, beef samples were extracted and profiled using non-targeted UPLC-MS analyses. Data analysis was conducted with Metaboanalyst 6.0. The correlation analysis was conduct with Pearson’s correlation and considered the significance level at P < 0.05. In brief, LL and ST maintained greater color stability, redox stability, and lipid/protein oxidative stabilities compared with BF and GM, with IF showing the least (P < 0.05). Also, IF had the greatest levels of mitochondrial-swelling, mitochondrial-lipid oxidation, and oxidized CytC compared with LL (P < 0.05). The ANOVA results found 1,410 significant features in the metabolome analysis and 531 in the lipidome analysis of beef samples. Utilizing partial least square-discriminant analysis (PLS-DA), scatter plots grouped the five muscle types into three distinct clusters: LL and ST, BF and GM, and IF. Pro-apoptotic factors such as phosphatidylserine and lysophosphatidylserine were greater in IF compared with LL and ST (P < 0.05). From the metabolome results, anti-apoptotic factors like creatine and glutathione were increased in LL and ST compared with IF, whereas pro-apoptotic spermidine and adenosine monophosphate (AMP) were greatest in IF (P < 0.05). CIE a* showed a positive correlation with phospholipids and mitochondria-swelling (P < 0.05). Chroma exhibited a positive correlation with TRA, creatine, cyclic AMP, and GMP (P < 0.05). The results suggest that variations in meat color stability among the five beef muscles were likely attributed to differences in the abundance of lipids and metabolites associated with redox and oxidative stabilities, as well as mitochondrial-mediated apoptotic pathways. Specifically, the varying abundance of pro-/anti-apoptotic factors across muscles indicates potential mechanistic biochemical linkages between the apoptosis and meat color. Further research is warranted to investigate the effects of extended aging periods on changes in apoptotic features and color stability of beef muscles.

Acetyl-CoA carboxylase inhibition increases retinal pigment epithelial cell fatty acid flux and restricts apolipoprotein efflux

Lipid-rich deposits called drusen accumulate under the retinal pigment epithelium (RPE) in the eyes of patients with age-related macular degeneration (AMD) and Sorsby’s fundus dystrophy (SFD). Drusen may contribute to photoreceptor and RPE degeneration in these blinding diseases. We hypothesize that stimulating β-oxidation of fatty acids could decrease the availability of lipid with which RPE cells can generate drusen. Inhibitors of acetyl-CoA carboxylase (ACC) stimulate β-oxidation and diminish lipid accumulation in fatty liver disease. In this report we test the hypothesis that an ACC inhibitor, Firsocostat, can diminish lipid deposition by RPE cells. We probed metabolism and cellular function in mouse RPE-choroid tissue and in cultured human RPE cells. We used 13C6-glucose, 13C16-palmitate, and gas chromatography-linked mass spectrometry to monitor effects of Firsocostat on glycolytic, Krebs cycle, and fatty acid metabolism. We quantified lipid abundance, apolipoprotein E (ApoE) and vascular endothelial growth factor (VEGF) release using liquid chromatography-mass spectrometry, enzyme-linked immunosorbent assays and localized ApoE deposits by immunostaining. RPE barrier function was assessed by trans-epithelial electrical resistance (TEER). Firsocostat-mediated ACC inhibition increases β-oxidation, decreases intracellular lipid levels, diminishes lipoprotein release, and increases TEER. When human serum or outer segments are used to stimulate lipoprotein release, fewer lipoproteins are released in the presence of either lipid source and Firsocostat. In a culture model of SFD, Firsocostat stimulates fatty acid oxidation, increases TEER, and decreases ApoE release. We conclude that Firsocostat remodels RPE metabolism and can limit lipid deposition. This suggests that ACC inhibition could be an effective strategy for diminishing pathologic drusen in the eyes of patients with AMD or SFD.

Extracellular Vesicle-Packaged ACSL4 Induces Hepatocyte Senescence to Promote Hepatocellular Carcinoma Progression.

Extracellular vesicles (EVs) derived from cancer cells are crucial mediators of intercellular communication during tumor progression. The cargo in tumor-derived EVs that facilitates the establishment of a tumor-supportive microenvironment could serve as a therapeutic target to improve cancer treatment. Here, we demonstrated that hepatocellular carcinoma (HCC) cells secreted the acyl-CoA synthetase ACSL4 in large extracellular vesicles (lEVs) to modulate tumor-microenvironment interactions that promote HCC progression. HCC-derived lEV ACSL4 increased the intracellular abundance of polyunsaturated fatty acid-containing lipids and remodeled the lipid profile to potentiate lipid peroxidation in peritumoral hepatocytes, resulting in hepatocyte senescence accompanied by the senescence-associated secretory phenotype (SASP). Depletion of senescent hepatocytes by senolytic treatment suppressed tumor progression. In HCC cells, SREBP2-mediated transcriptional activation upregulated ACSL4 expression, and Akt-mediated phosphorylation of ACSL4 induced its packaging into lEVs by augmenting its interaction with Annexin A2. This study identified the critical regulatory function of ACSL4 secreted from HCC cells in inducing lipid remodeling and senescence in hepatocytes to support HCC progression, suggesting that targeting lEV ACSL4 is a potential therapeutic strategy for HCC.

Lipid composition of coral propagules and reproductive material in coral restoration nurseries

Coral restoration efforts have rapidly increased worldwide, including the development of several programmes on the Great Barrier Reef (GBR) in recent years. While many restoration programmes utilise in-water nurseries to accelerate coral biomass yields, the impact of nursery environments on propagule quality has not been examined despite the importance of coral fitness for ensuring resistant populations. Here, we investigated two fitness indicators (lipid diversity and tissue protein abundance) of Acropora millepora adults and eggs grown on coral nurseries versus native reef on the GBR, with adults assessed at two sites (Blue Lagoon and Rayban) and eggs assessed at one site (Blue Lagoon). Lipid profiles of adult colonies varied by site and origin (nursery versus wild reef), with adult nursery corals exhibiting an elevated relative abundance of storage lipids (diacylglycerols and triacylglycerols) and lipid classes responsible for regulating membrane structure (phosphatidylcholines and sterol esters), while wild corals were characterised by a greater relative abundance of fatty acids and classes involved in immunoregulation. Comparing eggs from different origins, nursery offspring were richer in energy-storing triacylglycerols, as well as ceramides and phosphatidylcholines essential for membrane structure, while wild eggs had a greater relative abundance of wax ester species also important for energy storage. No differences were found in total protein abundance (adult or eggs) or egg physical characteristics (count and size) between nursery and wild origins. Variations in lipid profiles are consistent with differences in environmental conditions between reef sites and origin (nursery versus wild), highlighting the need to consider site selection and propagation conditions when planning restoration projects. Importantly, these findings demonstrate that the lipid classes with the highest relative abundance in A. millepora nursery and wild eggs differed from those in adults from the same origin, suggesting that propagation origin is more important for driving lipid profiles in coral eggs compared to parental effects.

Evaluating stability and bioactivity of Rehmannia-derived nanovesicles during storage

Plant-derived nanovesicles (PDNVs) have garnered growing attention in the biomedical field owing to their abundance in plant-derived ribonucleic acids (RNA), proteins, lipids and metabolites. The question about the preservation of PDNVs is a crucial and unavoidable concern in both experiments’ settings and their potential clinical application. The objective of this research was to examine the impact of varying storage temperatures on the stability and bioactivity of Rehmannia-derived nanovesicles (RDNVs). The results showed that RDNVs aggregated after 2 weeks of storage period at 4 °C, and the particle size of some RDNVs gradually increased with time, along with the increase of solution potential. After 2 months of storage, all RDNVs exhibited varying levels of aggregation irrespective of storage temperature. The bioactivities of nanovesicles under different temperature storage conditions revealed a gradual decline in cell proliferation inhibition bioactivity over time, significantly lower than that of freshly prepared RDNVs. In contrast, the preservation of anti-migratory activity in RDNVs was found to be more effective when subjected to rapid freezing in liquid nitrogen followed by storage at − 80 °C, as opposed to direct storage at − 80 °C. These findings suggest that temperature alone may not be sufficient in safeguarding the activity and stability of RDNVs, highlighting the necessity for the development of novel protective agents for PDNVs.

Chemodiversity of dissolved organic matter and its association with the bacterial community at a zinc smelting slag site after 10 years of direct revegetation

Dissolved organic matter (DOM) plays a critical role in driving the development of biogeochemical functions in revegetated metal smelting slag sites, laying a fundamental basis for their sustainable rehabilitation. However, the DOM composition at the molecular level and its interaction with the microbial community in such sites undergoing long-term direct revegetation remain poorly understood. This study investigated the chemodiversity of DOM and its association with the bacterial community in the rhizosphere and non-rhizosphere slags of four plant species (Arundo donax, Broussonetia papyrifera, Cryptomeria fortunei, and Robinia pseudoacacia) planted at a zinc smelting slag site for 10 years. The results indicated that the relative abundance of lipids decreased from 18 % to 5 %, while the relative abundance of tannins and lignins/CRAM-like substances increased from 4 % to 10 % and from 44 % to 64 % in the revegetated slags, respectively. The chemical stability of the organic matter in the rhizosphere slag increased due to the retention of recalcitrant DOM components, such as lignins, aromatics, and tannins. As the diversity and relative abundance of the bacterial community increased, particularly within the Proteobacteria, there was better utilization of recalcitrant components (e.g., lignins/CRAM-like compounds), but this utilization was not invariable. In addition, potential preference associations between specific bacterial OTUs and DOM molecules were observed, possibly stimulated by heavy metal bioavailability. Network analysis revealed complex connectivity and strong interactions between the bacterial community and DOM molecules. These specific interactions between DOM molecules and the bacterial community enable adaptation to the harsh conditions of the slag environment. Overall, these findings provide novel insights into the transformation of DOM chemodiversity at the molecular level at a zinc smelting slag sites undergoing long-term revegetation. This knowledge could serve as a crucial foundation for developing direct revegetation strategies for the sustainable rehabilitation of metal smelting slag sites.

Deep serum lipidomics identifies evaluative and predictive biomarkers for individualized glycemic responses following low-energy diet-induced weight loss: a PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World (PREVIEW) substudy

BackgroundWeight loss through lifestyle interventions, notably low-energy diets, offers glycemic benefits in populations with overweight-associated prediabetes. However, >50% of these individuals fail to achieve normoglycemia after weight loss. Circulating lipids hold potential for evaluating dietary impacts and predicting diabetes risk. ObjectivesThis study sought to identify serum lipids that could serve as evaluative or predictive biomarkers for individual glycemic changes following diet-induced weight loss. MethodsWe studied 104 participants with overweight-associated prediabetes, who lost ≥8% weight via a low-energy diet over 8 wk. High-coverage lipidomics was conducted in serum samples before and after the dietary intervention. The lipidomic recalibration was assessed using differential lipid abundance comparisons and partial least squares discriminant analyses. Associations between lipid changes and clinical characteristics were determined by Spearman correlation and Bootstrap Forest of ensemble machine learning model. Baseline lipids, predictive of glycemic parameters changes postweight loss, were assessed using Bootstrap Forest analyses. ResultsWe quantified 439 serum lipid species and 9 related organic acids. Dietary intervention significantly reduced diacylglycerols, ceramides, lysophospholipids, and ether-linked phosphatidylethanolamine. In contrast, acylcarnitines, short-chain fatty acids, organic acids, and ether-linked phosphatidylcholine increased significantly. Changes in certain lipid species (e.g., saturated and monounsaturated fatty acid-containing glycerolipids, sphingadienine-based very long-chain sphingolipids, and organic acids) were closely associated with clinical glycemic parameters. Six baseline bioactive sphingolipids primarily predicted changes in fasting plasma glucose. In addition, a number of baseline lipid species, mainly diacylglycerols and triglycerides, were predictive of clinical changes in hemoglobin A1c, insulin and homeostasis model assessment of insulin resistance. ConclusionsNewly discovered serum lipidomic alterations and the associated changes in lipid-clinical variables suggest broad metabolic reprogramming related to diet-mediated glycemic control. Novel lipid predictors of glycemic outcomes could facilitate early stratification of individuals with prediabetes who are metabolically less responsive to weight loss, enabling more tailored intervention strategies beyond 1-size-fits-all lifestyle modification advice.The PREVIEW lifestyle intervention study was registered at clinicaltrials.gov as NCT01777893 (https://clinicaltrials.gov/study/NCT01777893).

The functional and nutritional properties of a novel Monascus fermented rice rich in resistant starch

Rice high in resistant starch (RS) showed great benefits in preventing diabetes. Red mold rice (RMR) is a traditionally functional food in China, preparing RMR with high-RS rice might produce a novel RMR with better nutrients and promote the utilization of high-RS rice in the food industry. R4 with the highest RS content was the most prone to be fermented by Monascus. After fermentation, the total starch and protein contents were significantly decreased, while the RS, lipid, free glucan, total free amino acids (FAAs), and γ-aminobutyric acid (GABA) contents were remarkably increased. Concurrently, the phenolic content and antioxidation activity were enhanced greatly. The individual phenolic acids such as ferulic acid showed significantly positive correlations with the antioxidant activity. Besides the abundant lipids, FAAs, GABA, and strong antioxidant capacity, fermented R4 had the highest ferulic acid content. This study provided alternatives for producing novel RMR and widened applications of high-RS rice in innovative functional foods.