Lipid Remodeling Research Articles

Abstract 3063: Defining oncogene-specific metabolic vulnerabilities in a mouse model of hepatocellular carcinoma

Abstract Despite the continued success of advanced cancer therapies, hepatocellular carcinoma (HCC) represents a substantial challenge to current treatment modalities that are not sufficiently effective for the management of advanced disease. Metabolic reprogramming is a hallmark of cancer and many oncogenic signaling pathways impact on cellular metabolism. Here, we are investigating changes in metabolism in different oncogene-driven mouse models of liver cancer to identify selective metabolic vulnerabilities associated with HCC that could be implicated in tumor initiation and progression to be exploited for cancer therapy. Transposon-based vectors coding for different combinations of oncogenes, either Myc and Akt1Myr (CaMIA) or Myc and NrasG12V (CaMIN), were transduced by hydrodynamic tail vein injected into C57BL/6 mice. The resulting liver tumors and control livers were subjected to a comprehensive profiling of polar metabolites (metabolomics) and lipids (lipidomics and total fatty acids) as well as changes in gene expression (transcriptomics). Despite similar overall survival, the two models display marked differences in the presentation of the tumors, with CaMIA showing larger aggressive tumors, while CaMIN livers contain numerous small tumor nodules. Both models also showed evidence for the deregulation of intermediate metabolism, indicating activation of aerobic glycolysis and deregulation of glutamine metabolism. Lipidomic analysis revealed substantial lipidome remodeling in both models. Oncogene-specific alterations included elevated levels of lysophosphatidylcholine (LPC) in CaMIN tumors, while CaMIA tumors displayed high levels of ether phospholipids compared to CaMIN and normal liver. Moreover, the fraction of polyunsaturated fatty acids (PUFAs) was enhanced in lipids from CaMIN tumors, while monounsaturated fatty acids (MUFAs) were enriched in CaMIA tumors. Furthermore, tumors from both genotypes produced higher levels of oxylipins, a class of lipid mediators involved in signaling and inflammation, compared to normal liver. Transcriptome analysis confirmed these metabolic alterations and revealed evidence for enhanced inflammatory signaling in CaMIN. In addition, analysis of tumor microenvironment composition disclosed specific differences in stromal components, indicative of immune evasion through checkpoint activation. Experiments in primary murine liver cancer cell lines confirmed oncogene-specific metabolic rearrangements and suggest elevated sensitivity towards inhibitors of lipid remodeling. Future experiments will investigate the role of altered lipid metabolism in tumor development and immune evasion in liver cancer. Citation Format: Kamal Al-Shami, Marteinn Snaebjornsson, Felix Vogel, Lisa Schlicker, Phillip Pöller, Daniel Dauch, Almut Schulze. Defining oncogene-specific metabolic vulnerabilities in a mouse model of hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3063.

Functional and multi-omics signatures of mitapivat efficacy upon activation of pyruvate kinase in red blood cells from patients with sickle cell disease.

Mitapivat, a pyruvate kinase activator, shows great potential as a sickle cell disease (SCD)-modifying therapy. The safety and efficacy of mitapivat as a long-term maintenance therapy are currently being evaluated in two open-label studies. Here we applied a comprehensive multi-omics approach to investigate the impact of activating pyruvate kinase on red blood cells (RBC) from 15 SCD patients. HbSS patients were enrolled in one of the open-label, extended studies (NCT04610866). Leukodepleted RBC obtained from fresh whole blood at baseline, prior to drug initiation, and at longitudinal timepoints over the course of the study were processed for multi-omics through a stepwise extraction of metabolites, lipids and proteins. Mitapivat therapy had significant effects on the metabolome, lipidome and proteome of SCD RBC. Mitapivat decreased 2,3-diphosphoglycerate levels, increased adenosine triphosphate levels, and improved hematologic and sickling parameters in patients with SCD. Agreement between omics measurements and clinical measurements confirmed the specificity of mitapivat on targeting late glycolysis, with glycolytic metabolites ranking as the top correlates to parameters of hemoglobin S oxygen affinity (p50) and sickling kinetics (t50) during treatment. Mitapivat markedly reduced levels of proteins of mitochondrial origin within 2 weeks of initiation of treatment, with minimal changes in reticulocyte counts. In the first 6 months of treatment there were also transient elevations of lysophosphatidylcholines and oxylipins with depletion of free fatty acids, suggestive of an effect on membrane lipid remodeling. Multi-omics analysis of RBC identified benefits for glycolysis, as well as activation of the Lands cycle.

Phosphorus drives adaptive shifts in membrane lipid pools and synthesis between soils

Phospholipids are key constituents of microbial membranes and account for a substantial fraction of microbial P, while P-free betaine lipids provide a pathway for membrane synthesis independent of P. The aim of this study was to test if modulation of relative amounts of phospholipids vs P-free betaine lipids is a response to P availability. To examine responses of membrane lipids to P availability, we added P or P + C to an extremely P-poor sandstone-derived soil (total P = 41 μg g−1) and a higher P shale-derived soil (total P = 201 μg g−1). By using D2O labelling and LC-MS we were able to disentangle membrane lipid synthesis dependent on P (i.e. 2H incorporation into phospholipids) from membrane lipid synthesis independent of P (i.e. 2H incorporation into P-free betaine lipids). In unamended soils, P-free betaine lipids were almost 60% of the membrane lipid pool of the P-poor sandstone-derived soil, but only 10% of the higher-P shale-derived soil. Hence, to produce a unit of membrane lipid, the microbial population of sandstone soil required only 54% as much P as the microbial population of shale soil. Four days after adding P to the sandstone soil, phospholipids accounted for a larger proportion of the pool and synthesis of membrane lipids while pool and synthesis of P-free betaine lipids decreased. The increased allocation to phospholipids in sandstone soil amended with P likely reflected amelioration of P limitation given that P addition did not affect pools or synthesis of phospholipids versus betaine lipids in the higher-P shale soil. Collectively these data support the idea that having membranes with a high proportion of P-free betaine lipids is a key adaptive trait of microbial populations of P-poor soil, while the plasticity afforded by membrane lipid remodelling enables short-term fine-tuning of membrane lipid composition to P availability.

Shared and more specific genetic determinants and pathways underlying yeast tolerance to acetic, butyric, and octanoic acids

BackgroundThe improvement of yeast tolerance to acetic, butyric, and octanoic acids is an important step for the implementation of economically and technologically sustainable bioprocesses for the bioconversion of renewable biomass resources and wastes. To guide genome engineering of promising yeast cell factories toward highly robust superior strains, it is instrumental to identify molecular targets and understand the mechanisms underlying tolerance to those monocarboxylic fatty acids. A chemogenomic analysis was performed, complemented with physiological studies, to unveil genetic tolerance determinants in the model yeast and cell factory Saccharomyces cerevisiae exposed to equivalent moderate inhibitory concentrations of acetic, butyric, or octanoic acids.ResultsResults indicate the existence of multiple shared genetic determinants and pathways underlying tolerance to these short- and medium-chain fatty acids, such as vacuolar acidification, intracellular trafficking, autophagy, and protein synthesis. The number of tolerance genes identified increased with the linear chain length and the datasets for butyric and octanoic acids include the highest number of genes in common suggesting the existence of more similar toxicity and tolerance mechanisms. Results of this analysis, at the systems level, point to a more marked deleterious effect of an equivalent inhibitory concentration of the more lipophilic octanoic acid, followed by butyric acid, on the cell envelope and on cellular membranes function and lipid remodeling. The importance of mitochondrial genome maintenance and functional mitochondria to obtain ATP for energy-dependent detoxification processes also emerged from this chemogenomic analysis, especially for octanoic acid.ConclusionsThis study provides new biological knowledge of interest to gain further mechanistic insights into toxicity and tolerance to linear-chain monocarboxylic acids of increasing liposolubility and reports the first lists of tolerance genes, at the genome scale, for butyric and octanoic acids. These genes and biological functions are potential targets for synthetic biology approaches applied to promising yeast cell factories, toward more robust superior strains, a highly desirable phenotype to increase the economic viability of bioprocesses based on mixtures of volatiles/medium-chain fatty acids derived from low-cost biodegradable substrates or lignocellulose hydrolysates.

Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate Enhances foxo1-Mediated Lipophagy to Remodel Lipid Metabolism in Zebrafish Liver.

An emerging environmental contaminant, bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), can bioaccumulate in the liver and affect hepatic lipid metabolism. However, the in-depth mechanism has yet to be comprehensively explored. In this study, we utilized transgenic zebrafish Tg (Apo14: GFP) to image the interference of TBPH on zebrafish liver development and lipid metabolism at the early development stage. Using integrated lipidomic and transcriptomic analyses to profile the lipid remodeling effect, we uncovered the potential effects of TBPH on lipophagy-related signaling pathways in zebrafish larvae. Decreased lipid contents accompanied by enhanced lipophagy were confirmed by the measurements of Oil Red O staining and transmission electron microscopy in liver tissues. Particularly, the regulatory role of the foxo1 factor was validated via its transcriptional inhibitor. Double immunofluorescence staining integrated with biochemical analysis indicated that the enhanced lipophagy and mitochondrial fatty acid oxidation induced by TBPH were reversed by the foxo1 inhibitor. To summarize, our study reveals, for the first time, the essential role of foxo1-mediated lipophagy in TBPH-induced lipid metabolic disorders and hepatoxicity, providing new insights for metabolic disease studies and ecological health risk assessment of TBPH.

Jasmonates and Ethylene Shape Floridoside Synthesis during Carposporogenesis in the Red Seaweed Grateloupia imbricata.

Floridoside is a galactosyl-glycerol compound that acts to supply UDP-galactose and functions as an organic osmolyte in response to salinity in Rhodophyta. Significantly, the UDP-galactose pool is shared for sulfated cell wall galactan synthesis, and, in turn, affected by thallus development alongside carposporogenesis induced by volatile growth regulators, such as ethylene and methyl jasmonate, in the red seaweed Grateloupia imbricata. In this study, we monitored changes in the floridoside reservoir through gene expression controlling both the galactose pool and glyceride pool under different reproductive stages of G. imbricata and we considered changing salinity conditions. Floridoside synthesis was followed by expression analysis of galactose-1-phosphate uridyltransferase (GALT) as UDP-galactose is obtained from UDP-glucose and glucose-1P, and through α-galactosidase gene expression as degradation of floridoside occurs through the cleavage of galactosyl residues. Meanwhile, glycerol 3-phosphate is connected with the galactoglyceride biosynthetic pathway by glycerol 3-phosphate dehydrogenase (G3PD), monogalactosyl diacylglyceride synthase (MGDGS), and digalactosyl diacylglyceride synthase (DGDGS). The results of our study confirm that low GALT transcripts are correlated with thalli softness to locate reproductive structures, as well as constricting the synthesis of UDP-hexoses for galactan backbone synthesis in the presence of two volatile regulators and methionine. Meanwhile, α-galactosidase modulates expression according to cystocarp maturation, and we found high transcripts in late development stages, as occurred in the presence of methyljasmonate, compared to early stages in ethylene. Regarding the acylglyceride pool, the upregulation of G3PD, MGDGS, and DGDGS gene expression in G. imbricata treated with MEJA supports lipid remodeling, as high levels of transcripts for MGDGS and DGDGS provide membrane stability during late development stages of cystocarps. Similar behavior is assumed in three naturally collected thalli development stages-namely, fertile, fertilized, and fertile-under 65 psu salinity conditions. Low transcripts for α-galactosidase and high for G3PD are reported in infertile and fertilized thalli, which is the opposite to high transcripts for α-galactosidase and low for G3PD encountered in fertile thalli within visible cystocarps compared to each of their corresponding stages in 35 psu. No significant changes are reported for MGDGS and DGDGS. It is concluded that cystocarp and thallus development stages affect galactose and glycerides pools with interwoven effects on cell wall polysaccharides.

Bacteroides fragilis aggravates high-fat diet-induced non-alcoholic fatty liver disease by regulating lipid metabolism and remodeling gut microbiota.

Gut microbiota dysbiosis is a prominent determinant that significantly contributes to the disruption of lipid metabolism. Consequently, it is essential to the occurrence and development of non-alcoholic fatty liver disease (NAFLD). Nevertheless, the connection between diet and symbiotic gut microbiota in the progression of NAFLD remains uncertain. The purpose of this study was to explore the role of supplementing commensal Bacteroides fragilis (B. fragilis) on lipid metabolism, gut microbiota, and metabolites in high-fat diet (HFD)-fed mice, elucidating the impact of gut microbiota and metabolites on the development of NAFLD. Our study revealed that supplementation with B. fragilis exacerbated both weight gain and obesity in mice. B. fragilis exacerbated blood glucose levels and liver dysfunction in mice. Furthermore, an increase in liver lipid accumulation and the upregulation of genes correlated with lipid metabolism were observed in mice. Under an HFD, supplementation of commensal B. fragilis resulted in alterations in the gut microbiota, notably a significant increase in Desulfovibrionaceae, which led to elevated endotoxin levels and thereby influenced the progression of NAFLD. It was interesting that the simultaneous examination of gut microbiota metabolites revealed a more pronounced impact of diet on short-chain fatty acids. This study represented the pioneering investigation into the impact of B. fragilis on NAFLD. Our findings demonstrated that B. fragilis induced dysregulation in the intestinal microbiota, leading to elevated levels of lipopolysaccharide and dysfunction in glucose and lipid metabolism, thereby exacerbating NAFLD.IMPORTANCESome intestinal symbiotic microbes are involved in the occurrence of the metabolic disorders. Our study investigated the impact of supplementing commensal Bacteroides fragilis on host metabolism in high-fat diet-fed mice. Research results indicated that adding a specific bacterial strain to the complex intestinal microecology can worsen metabolic conditions. This effect mainly affects the structural diversity of intestinal microorganisms, the increase in harmful bacteria in the gut, and the elevation of endotoxin levels, blood glucose, and lipid metabolism, thereby impacting the progression of non-alcoholic fatty liver disease (NAFLD). Understanding the principles that govern the establishment of microbial communities comprising multiple species is crucial for preventing or repairing dysfunctions in these communities, thereby enhancing host health and facilitating disease treatment. This study demonstrated that gut microbiota dysbiosis could contribute to metabolic dysfunction and provides new insights into how to promote gut microbiota in the prevention and therapy of NAFLD.

Myomerger Induces Membrane Hemifusion and Regulates Fusion Pore Expansion.

Membrane fusion is a crucial mechanism in a wide variety of important events in cell biology from viral infection to exocytosis. However, despite many efforts and much progress, cell-cell fusion has remained elusive to our understanding. Along the life of the fusion pore, large conformational changes take place from the initial lipid bilayer bending, passing through the hemifusion intermediates, and ending with the formation of the first nascent fusion pore. In this sense, computer simulations are an ideal technique for describing such complex lipid remodeling at the molecular level. In this work, we studied the role played by the muscle-specific membrane protein Myomerger during the formation of the fusion pore. We have conducted μs length atomistic and coarse-grained molecular dynamics, together with free-energy calculations using ad hoc collective variables. Our results show that Myomerger favors the hemifusion diaphragm-stalk transition, reduces the nucleation-expansion energy difference, and promotes the formation of nonenlarging fusion pores.

Spatial MS multiomics on clinical prostate cancer tissues.

Mass spectrometry (MS) and MS imaging (MSI) are used extensively for both the spatial and bulk characterization of samples in lipidomics and proteomics workflows. These datasets are typically generated independently due to different requirements for sample preparation. However, modern omics technologies now provide higher sample throughput and deeper molecular coverage, which, in combination with more sophisticated bioinformatic and statistical pipelines, make generating multiomics data from a single sample a reality. In this workflow, we use spatial lipidomics data generated by matrix-assisted laser desorption/ionization MSI (MALDI-MSI) on prostate cancer (PCa) radical prostatectomy cores to guide the definition of tumor and benign tissue regions for laser capture microdissection (LCM) and bottom-up proteomics all on the same sample and using the same mass spectrometer. Accurate region of interest (ROI) mapping was facilitated by the SCiLS region mapper software and dissected regions were analyzed using a dia-PASEF workflow. A total of 5525 unique protein groups were identified from all dissected regions. Lysophosphatidylcholine acyltransferase 1 (LPCAT1), a lipid remodelling enzyme, was significantly enriched in the dissected regions of cancerous epithelium (CE) compared to benign epithelium (BE). The increased abundance of this protein was reflected in the lipidomics data with an increased ion intensity ratio for pairs of phosphatidylcholines (PC) and lysophosphatidylcholines (LPC) in CE compared to BE.

M2 tumor-associated macrophages and CXCL2 induce lipid remodeling in hepatocellular carcinoma cell lines.

Primary hepatocellular carcinoma (HCC) is one of the most common malignant tumors, but its pathogenesis remains incompletely elucidated. Recently, many studies indicated that lipid remodeling plays an important role in the occurrence and development of HCC. Furthermore, lipids have been proven to be indispensable mediators in promoting communication between tumor cells and extracellular matrix in the tumor microenvironment. Thus, this study aims to comprehensively investigate the process of lipid remodeling during HCC metastasis based on the LC-electrospray ionization-MS (LC-ESI-MS) combined with multiple reaction monitoring technology. M2 tumor-associated macrophages and the recombinant human protein CXCL2 were used to simulate the tumor microenvironment. After co-incubating SMMC7721 and MHCC97-H cell lines with M2 tumor-associated macrophages or the recombinant human protein CXCL2 for 48 h, LC-ESI-MS was used to quantify the levels of two major classes of lipid molecules, namely, glycerophospholipids and sphingolipids. Our results suggest that lipid remodeling in the tumor microenvironment may promote the migration and invasion of HCC cell lines.

Lipid remodelling and the conversion of lipids into sugars associated with tolerance to cadmium toxicity during white clover seed germination.

Cadmium (Cd) is a leading environmental issue worldwide. The current study was conducted to investigate Cd tolerance of 10 commercial white clover (Trifolium repens) cultivars during seed germination and to further explore differences in lipid remodelling, glycometabolism, and the conversion of lipids into sugars contributing to Cd tolerance in the early phase of seedling establishment as well as the accumulation of Cd in seedlings and mature plants. The results show that Cd stress significantly reduced seed germination of 10 cultivars. Compared to Cd-sensitive Sulky, Cd-tolerant Pixie accelerated amylolysis to produce more glucose, fructose, and sucrose by maintaining higher amylase and sucrase activities under Cd stress. Pixie maintained higher contents of various lipids, higher DGDG/MGDG ratio, and lower unsaturation levels of lipids, which could be beneficial to membrane stability and integrity as well as signal transduction in cells after being subjected to Cd stress. In addition, Pixie upregulated expression levels of key genes (TrACX1, TrACX4, TrSDP6, and TrPCK1) involved in the conversion of lipids into sugars for early seedling establishment under Cd stress. These findings indicate that lipid remodelling, enhanced glycometabolism, and accelerated conversion of lipids into sugars are important adaptive strategies for white clover seed germination and subsequent seedling establishment under Cd stress. In addition, Pixie not only accumulated more Cd in seedlings and mature plants than Sulky but also had significantly better growth and phytoremediation efficiency under Cd stress. Pixie could be used as a suitable and critical germplasm for the rehabilitation and re-establishment of Cd-contaminated areas.

Lipid remodelling in mammalian development.

Lipid remodelling in mammalian development.

Upregulated selenoprotein I during lipopolysaccharide-induced B cell activation promotes lipidomic changes and is required for effective differentiation into IgM-secreting plasma B cells.

The mechanisms driving metabolic reprogramming during B cell activation are unclear, particularly roles for enzymatic pathways involved in lipid remodeling. We found that murine B cell activation with lipopolysaccharide (LPS) led to a 1.6-fold increase in total lipids that included higher levels of phosphatidylethanolamine (PE) and plasmenyl PE. Selenoprotein I (SELENOI) is an ethanolamine phospholipid transferase involved in the synthesis of both PE and plasmenyl PE, and SELENOI expression was also upregulated during activation. Selenoi knockout (KO) B cells exhibited decreased levels of plasmenyl PE, which plays an important antioxidant role. Lipid peroxidation was measured and found to increase ∼2-fold in KO vs. wild-type (WT) B cells. Cell death was not impacted by KO in LPS-treated B cells and proliferation was only slightly reduced, but differentiation into CD138 + Blimp-1+ plasma B cells was decreased ∼2-fold. This led to examination of B cell receptors important for differentiation that recognize the ligand B cell activating factor, and levels of TACI (transmembrane activator, calcium-modulator, and cytophilin ligand interactor) (CD267) were significantly decreased on KO B cells compared with WT control cells. Vaccination with ovalbumin/adjuvant led to decreased ovalbumin-specific immunoglobulin M (IgM) levels in sera of KO mice compared with WT mice. Real-time polymerase chain reaction analyses revealed a decreased switch from surface to secreted IgM in spleens of KO mice induced by vaccination or LP-BM5 retrovirus infection. Overall, these findings detail the lipidomic response of B cells to LPS activation and reveal the importance of upregulated SELENOI for promoting differentiation into IgM-secreting plasma B cells.

Dietary (poly)phenols as modulators of the biophysical properties in endothelial cell membranes: its impact on nitric oxide bioavailability in hypertension.

Hypertension is a major contributor to premature death, owing to the associated increased risk of damage to the heart, brain and kidneys. Although hypertension is manageable by medication and lifestyle changes, the risk increases with age. In an increasingly aged society, the incidence of hypertension is escalating, and is expected to increase the prevalence of (cerebro)vascular events and their associated mortality. Adherence to plant-based diets improves blood pressure and vascular markers in individuals with hypertension. Food flavonoids have an inhibitory effect towards angiotensin-converting enzyme (ACE1) and although this effect is greatly diminished upon metabolization, their microbial metabolites have been found to improve endothelial nitric oxide synthase (eNOS) activity. Considering the transmembrane location of ACE1 and eNOS, the ability of (poly)phenols to interact with membrane lipids modulate the cell membrane's biophysical properties and impact on nitric oxide (·NO) synthesis and bioavailability, remain poorly studied. Herein, we provide an overview of the current knowledge on the lipid remodeling of endothelial membranes with age, its impact on the cell membrane's biophysical properties and ·NO permeability across the endothelial barrier. We also discuss the potential of (poly)phenols and other plant-based compounds as key players in hypertension management, and address the caveats and challenges in adopted methodologies.

Membrane Epilipidome-Lipid Modifications, Their Dynamics, and Functional Significance.

Lipids are characterized by extremely high structural diversity translated into a wide range of physicochemical properties. As such, lipids are vital for many different functions including organization of cellular and organelle membranes, control of cellular and organismal energy metabolism, as well as mediating multiple signaling pathways. To maintain the lipid chemical diversity and to achieve rapid lipid remodeling required for the responsiveness and adaptability of cellular membranes, living systems make use of a network of chemical modifications of already existing lipids that complement the rather slow biosynthetic pathways. Similarly to biopolymers, which can be modified epigenetically and posttranscriptionally (for nucleic acids) or posttranslationally (for proteins), lipids can also undergo chemical alterations through oxygenation, nitration, phosphorylation, glycosylation, etc. In this way, an expanded collective of modified lipids that we term the "epilipidome," provides the ultimate level of complexity to biological membranes and delivers a battery of active small-molecule compounds for numerous regulatory processes. As many lipid modifications are tightly controlled and often occur in response to extra- and intracellular stimuli at defined locations, the emergence of the epilipidome greatly contributes to the spatial and temporal compartmentalization of diverse cellular processes. Accordingly, epilipid modifications are observed in all living organisms and are among the most consistent prerequisites for complex life.

Differences in membrane lipid homeostasis confer contrast tolerance to low phosphorus in two wheat (Triticum aestivum L.) cultivars

Although lipids are involved in plant adaptation to phosphorus (P) deficiency, the underlying relationships are not fully understood, especially in wheat. Thus, a comparative study of changes in leaf lipid content, composition and implicated gene expression during low-P was conducted hydroponically using two wheat cultivars differing in low-P tolerance. Low-P reduced phospholipid content but increased digalactosyldoacylglycerol (DGDG) and sulfoquinovosyldiacylglycerol (SQDG) content in older fully unfolded leaves (OL), with ND2419 (tolerant) showing greater changes than ZM366 (sensitive), suggesting a greater capacity to recycle internal P in ND2419. Interestingly, a novel lipid remodeling pattern was detected in the youngest unfolded leaf (YL) of ND2419, which reduced less in phospholipid content but accumulated more DGDG and SQDG with higher unsaturation levels than ZM366. These changes favored better chloroplast development, functionality and membrane integrity of ND2419, which together improved low-P tolerance. The expression of genes encoding glycolipid synthases and enzymes involved in phospholipid biosynthesis and degradation explained the lipid changes. Furthermore, our findings indicate that phospholipid loss in OL is primarily caused by enhanced degradation, whereas that in YL is driven by decreased biosynthesis and increased degradation. The detailed description of the changes in lipid profiles and gene expression under low P provides a basis for improving wheat low-P tolerance.

Light intensity influences the glycerolipid remodeling of Gracilariopsis lemaneiformis in response to short-term high temperature stress

Temperature and light are two pivotal environmental factors for the growth of marine photosynthetic organisms. While the responses of Gracilariopsis lemaneiformis to individual high temperature or light stress have been explored, our understanding of its combined stress responses remains limited. This study aimed to investigate the combined effects of short-term high temperature (33 °C, 8 h) and different light intensities, that is, low light (LL, 50 μmol photon m−2 s−1), medium light (ML, 150 μmol photon m−2 s−1), and high light (HL, 300 μmol photon m−2 s−1), on the physiological responses and lipid remodeling of G. lemaneiformis. Results demonstrated that short-term exposure to either high temperature or high light stress led to a reduction in maximum (Fv/Fm), effective photochemical efficiency (Fv'/Fm') and maximum relative electron transfer rate (rETRmax), and the combination of these stresses exerted a more pronounced inhibitory effect on photosystem II efficiency. Short-term exposure to heat stress led to an increase in superoxide dismutase (SOD) activity, as well as a rise in glutathione (GSH) and ascorbate (Asc) contents under LL, while the activities of antioxidant enzymes (SOD, peroxidase, and ascorbate peroxidase) and levels of non-enzymatic antioxidants (GSH and Asc) were reduced under ML and HL. Additionally, short-term heat stress induced the accumulations of phosphatidylcholine (PC), phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, sulfoquinovosyldiacylglycerol, and triacylglycerol (TAG) under LL, while heat-induced lipid accumulation decreased under ML and HL. Furthermore, heat stress increased the accumulation of saturated or unsaturated PC species under LL. Specifically, there was an increase in the levels of saturated or monounsaturated acyl chain–containing PC species, whereas the levels of polyunsaturated acyl chain-containing PC species declined under ML and HL. Correspondingly, a significant increase in TAG species with polyunsaturated acyl chains was observed, particularly under LL conditions, suggesting a potential lipid turnover between PC and TAG. These results showed that the lipid metabolic plasticity of G. lemaneiformis enabled it to rapidly adapt to fluctuating environmental conditions, and the light environment regulated its heat stress response.

Integrated transcriptome and metabolome analysis reveals the divergent evolution of low-P tolerance in cultivated and Tibetan wild barley

Most arable lands in the world are quite low in available phosphorus (P), becoming an important factor restricting crop yield. However, the genotypic difference of low-P tolerance in barley is rarely understood at molecular level. In this study, low-P responses of three barley genotypes were explored by physiological, transcriptomic and metabolomic analysis. The results showed that low-P-tolerant genotypes Zaoaibai (cultivar) and X130 (Tibetan wild accession) showed less growth inhibition compared to low-P-sensitive Salooni2 under low-P stress. Omics analysis showed that many genes involved in Pi acquisition and transport were more upregulated in Zaoaibai, which had relatively higher concentrations of shoot P and glucose-6-phosphate, indicating that enhancement of P acquisition, P translocation and P availability contributed to low-P tolerance in Zaoaibai. On the other hand, the genes and metabolites involved in biosynthesis of Pi-free lipids were highly expressed and more abundant in X130, suggesting that remodeling of membrane lipids by replacing phospholipids with Pi-free lipids is an important strategy for X130 in its adaptation to low-P stress. The divergent evolution of low-P tolerance in Zaoaibai and X130 could be driven by diverse ecological factors in Eastern China (low soil P) and Tibet Plateau (high soil P and low temperature), respectively.

Widely targeted quantitative lipidomics reveal lipid remodeling in adipose tissue after long term of the combined exposure to bisphenol A and fructose.

Adipose tissue is the main organ that stores lipids and it plays important roles in metabolic balance in the body. We recently reported in Human and Experimental Toxicology that the combined exposure to BPA and fructose may interfere with energy metabolism of adipose tissue. However, it is still unclear whether the combined exposure to BPA and fructose has the possibility to induce lipid remodeling in adipose tissue. In the present study, we performed a widely targeted quantitative lipidomic analysis of the adipose tissue of rats after 6 months of BPA and fructose combined exposure. We totally determined 734 lipid molecules in the adipose tissue of rats. Principal component analysis (PCA) showed the group of the combined exposure to higher-dose (25μg/kg every other day) BPA and fructose can be distinguished from the groups of control, higher-dose BPA exposure and fructose exposure clearly. Partial least squares-discriminant analysis (PLS-DA) and univariate statistical analysis displayed lipids of PC(18:0_ 20:3), TG(8:0_14:0_16:0), TG(12:0_14:0_16:1), TG(10:0_16:0_16:1), TG(12:0_ 14:0_18:1), TG(14:0_ 16:0_16:1), TG(14:0_14:1_16:1), TG(8:0_ 16:1_16:2), TG(14:1_16:1_ 16:1), TG(16:1_18:1_18:1), TG(16:0_16:1_20:4) and TG(15:0_18:1_ 24:1) may contributed the most to the discrimination. These findings indicated that combined exposure to BPA and fructose has the potential to cause lipid remodeling in adipose tissue.

Decoding the role of mycobacterial lipid remodelling and membrane dynamics in antibiotic tolerance.

Current treatments for tuberculosis primarily target Mycobacterium tuberculosis (Mtb) infections, often neglecting the emerging issue of latent tuberculosis infection (LTBI) which are characterized by reduced susceptibility to antibiotics. The bacterium undergoes multiple adaptations during dormancy within host granulomas, leading to the development of antibiotic-tolerant strains. The mycobacterial membrane plays a crucial role in drug permeability, and this study aims to characterize membrane lipid deviations during dormancy through extensive lipidomic analysis of bacteria cultivated in distinct media and growth stages. The results revealed that specific lipids localize in different regions of the membrane envelope, allowing the bacterium to adapt to granuloma conditions. These lipid modifications were then correlated with the biophysical properties of the mycomembrane, which may affect interactions with antibiotics. Overall, our findings offer a deeper understanding of the bacterial adaptations during dormancy, highlighting the role of lipids in modulating membrane behaviour and drug permeability, ultimately providing the groundwork for the development of more effective treatments tailored to combat latent infections.