Biosynthesis Of Unsaturated Fatty Acids Research Articles

ABSCISIC ACID-INSENSITIVE 5-ω3 FATTY ACID DESATURASE3 module regulates unsaturated fatty acids biosynthesis in Paeonia ostii

Paeonia ostii is an authorized novel vegetable oil crop due to its seeds rich in unsaturated fatty acids (UFAs) especially α-linolenic acid (ALA), which overweight the current available edible oil. However, little is known on the regulation mechanism of UFAs biosynthesis during its seed development. Here, we used transcriptome and proteome data combining phytochemistry means to uncover the relationship between abscisic acid (ABA) signaling and UFAs biosynthesis during P. ostii seed development. Based on transcriptome and proteome analysis, two desaturases of omega-6 and omega-3 fatty acid, named as PoFAD2 and PoFAD3 responsible for ALA biosynthesis were identified. Then, an ABSCISIC ACID-INSENSITIVE 5 (ABI5) proteins was identified as an upstream transcriptional factor, which activated the expression of PoFAD3 instead of PoFAD2. Moreover, silencing of PoABI5 repressed the response of PoFAD3 to ABA. This study provides the first view on the connection between the function of ABA signaling factors and ALA biosynthesis in the P. ostii seed, which lays the foundation for studies on the regulatory mechanism of ABA signaling involved in the UFAs synthesis during seeds development, meanwhile, it will shed light on manipulation of ALA content for satisfying human demands on high quality of edible oil or healthy supplement.

The dysregulation of unsaturated fatty acid-based metabolomics in the MNNG-induced malignant transformation of Het-1A cells.

Studies have shown that environmental carcinogens exerted an important function in the high incidence of esophageal cancer (EC). Nitrosamines have been identified as important environmental carcinogens for EC. This study aimed to investigate the metabolic disturbances and new key toxicological markers in the malignant transformation process of normal esophageal epithelial cells (Het-1A) induced by MNNG (N-methyl-N'-nitro-N-nitrosoguanidine). Untargeted metabolomic and lipidomic profiling analysis by using ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS) were applied to explore the metabolic network alterations of Het-1A cells. The metabolomic results showed that significant alterations were observed in metabolic signatures between different generations (P5, P15, P25, P35) and the control cell group (P0). A total of 48 differential endogenous metabolites were screened and identified, mainly containing fatty acids, amino acids, and nucleotides. The differential metabolites were predominantly linked to the pathway of biosynthesis of unsaturated fatty acids metabolism. The cell lipidomic profiling revealed that the most differential lipids contained fatty acids (FAs), phosphatidylcholines (PC), phosphatidylethanolamines (PE), and phosphatidylserines (PS). The enrichment of the lipidomic pathway also confirmed that the lipid metabolism of biosynthesis of unsaturated fatty acids was the significant variation during the cell malignant transformation. Furthermore, we detected the expression of the upstream regulatory enzymes related to the unsaturated fatty acids to explore the regulation mechanism. The expression of stearoyl-CoA desaturase (SCD), ELOVL fatty acid elongase 1 (ELOVL1) promoted, and fatty acid desaturase 1 (FADS1) inhibited the key fatty acids of unsaturated fatty acids metabolism compared to the control cell group. Overall, our results revealed that lipid fatty acid metabolism was involved in the malignant transformation of Het-1A cells induced by MNNG and deepened the awareness of the carcinogenic mechanism of environmental exposure pollutants.

Population Evolution, Genetic Diversity and Structure of the Medicinal Legume, Glycyrrhiza uralensis and the Effects of Geographical Distribution on Leaves Nutrient Elements and Photosynthesis.

Glycyrrhiza uralensis is a valuable medicinal legume, which occurs widely in arid and semi-arid regions. G. uralensis demand has risen steeply due to its high medical and commercial value. Interpret genome-wide information can stimulate the G. uralensis development as far as its increased bioactive compound levels, and plant yield are concerned. In this study, leaf nutrient concentration and photosynthetic chlorophyll index of G. uralensis were evaluated to determine the G. uralensis growth physiology in three habitats. We observed that G. uralensis nutrient levels and photosynthesis differed significantly in three regions (p < 0.05). Whole-genome re-sequencing of the sixty G. uralensis populations samples from different habitats was performed using an Illumina HiSeq sequencing platform to elucidate the distribution patterns, population evolution, and genetic diversity of G. uralensis. 150.06 Gb high-quality clean data was obtained after strict filtering. The 895237686 reads were mapped against the reference genome, with an average 89.7% mapping rate and 87.02% average sample coverage rate. A total of 6985987 SNPs were identified, and 117970 high-quality SNPs were obtained after filtering, which were subjected to subsequent analysis. Principal component analysis (PCA) based on interindividual SNPs and phylogenetic analysis based on interindividual SNPs showed that the G. uralensis samples could be categorized into central, southern, and eastern populations, which reflected strong genetic differentiation due to long periods of geographic isolation. In this study, a total of 131 candidate regions were screened, and 145 candidate genes (such as Glyur001802s00036258, Glyur003702s00044485, Glyur001802s00036257, Glyur007364s00047495, Glyur000028s00003476, and Glyur000398s00034457) were identified by selective clearance analysis based on Fst and θπ values. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed significant enrichment of 110 GO terms including carbohydrate metabolic process, carbohydrate biosynthetic process, carbohydrate derivative biosynthetic process, and glucose catabolic process (p < 0.05). Alpha-linolenic acid metabolism, biosynthesis of unsaturated fatty acids, and fatty acid degradation pathways were significantly enriched (p < 0.05). This study provides information on the genetic diversity, genetic structure, and population adaptability of the medicinal legumes, G. uralensis. The data obtained in this study provide valuable information for plant development and future optimization of breeding programs for functional genes.

Whole body vibration activates AMPK/CPT1 signaling pathway of skeletal muscle in young and aging mice based on metabolomics study.

Whole-body vibration (WBV) can improve skeletal muscle function in aging mice, but whether the effect on young and aging skeletal muscle is consistent has not been studied. We selected C57BL/6J mouse models, which were divided into young control group (YC), young vibration group (YV), aging control group (AC) and aging vibration group (AV). After 12 weeks of WBV, we found that compared with the YC group, the pathways of linoleic acid metabolism, biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, nicotinate and nicotinamide metabolism, glycine, serine and threonine metabolism, and arginine and proline metabolism improved significantly in the YV group. Compared with the AC group, the pathways of arachidonic acid metabolism, alpha-linolenic acid metabolism, biosynthesis of unsaturated fatty acids, pentose and glucuronate interconversions and pentose phosphate pathway improved significantly in the AV group. Furthermore, we found that WBV decreased triglyceride (TG), total cholesterol (TC), and free fatty acid (FFA) levels in aging mice, improved mitochondrial membrane potential, and increased the expression of phosphorylated activated protein kinase (p-AMPK), peroxisome proliferator-activated receptor coactivator-1α (PGC-1α) and carnitine palmitoyl transferase 1B (CPT1B) in the skeletal muscle of young and aging mice. Our study revealed that WBV mainly improved lipid metabolism and amino acid metabolism pathways of skeletal muscle in young mice and mainly improved lipid metabolism and glucose metabolism pathways of skeletal muscle in aging mice. WBV can activate the AMPK/CPT1 signaling pathway and improve mitochondrial function in skeletal muscle in both young and aging mice.

Metabolomics reveals that CAF-derived lipids promote colorectal cancer peritoneal metastasis by enhancing membrane fluidity.

Patients with peritoneal metastasis (PM) of colorectal cancer (CRC) have poorer overall survival outcomes than those without PM. Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment and mediate CRC progression and PM. It is imperative to identify and develop novel therapeutic targets for PM-CRC driven by CAFs. Using lipidomics, we reveal that the abundance of phosphatidylcholine (PC) with unsaturated acyl chains was increased in clinical PM-CRC specimens. Additionally, we found that CAFs were present at a higher relative abundance in primary PM-CRC tumors and that membrane fluidity in CRC cells was increased after incubation with CAF-conditioned medium (CM) through three independent methods: lipidomics, fluorescence recovery after photobleaching (FRAP), and generalized polarization. Then, we found that increased membrane fluidity can enhance glucose uptake and metabolism, as supported by real-time bioenergetics analysis and U-13C glucose labeling. Interestingly, stearoyl-CoA desaturase 1 (SCD), the rate-limiting enzyme in the biosynthesis of unsaturated fatty acids (uS-FAs), was expressed at low levels in PM and associated with poor prognosis in CRC patients. Importantly, by untargeted metabolomics analysis and fatty acid ([U-13C]-stearic acid) tracing analyses, we found that CRC cells take up lipids and lipid-like metabolites secreted from CAFs, which may compensate for low SCD expression. Both in vitro and in vivo experiments demonstrated that sodium palmitate (C16:0) treatment could decrease the CAF-induced change in cell membrane fluidity, limit glucose metabolism, suppress cell invasiveness, and impair tumor growth and intraperitoneal dissemination. An increased C16:0 concentration was shown to induce apoptosis linked to lipotoxicity. Furthermore, C16:0 effectively enhanced the antitumor activity of 5-fluorouracil (5-FU) in vitro and was well tolerated in vivo. Taken together, these findings suggest that adding the saturated fatty acid (S-FA) C16:0 to neoadjuvant chemotherapy may open new opportunities for treating PM-CRC in the future.

Compound green tea (CGT) regulates lipid metabolism in high-fat diet induced mice.

This work aims to study the effect of compound green tea (CGT) on liver lipid metabolism in mice based on metabolomics of liquid chromatography-mass spectrometry (LC-MS), and preliminarily identify potential biomarkers and pathways of action by using a metabonomic network database to explore the lipid-lowering effect of CGT. In this study, forty mice were randomly divided into four groups: compound tea treatment group (DH), high-fat model control group (NK), normal control group (CK) and positive drug group (YK). After a month of different interventions, the mice were weighed and the blood lipid indexes were detected. In addition, differential liver metabolites were monitored by using LC-MS. The results showed that CGT and positive drug treatment were able to decrease body weight, liver coefficient, TC, TG and LDL levels of obese mice, while increasing HDL levels. Among the 110 compounds obtained, 54 metabolites were significantly altered in the four comparisons. More importantly, 15 remarkably downregulated metabolites involved in Lysopc 16:1, Lysopc 18:1, and Lysopc 18:2 were found in the DH group when the mice were treated with CGT; meanwhile, the positive drug Xuezhikang was able to significantly downregulate 14 compounds, including (±)18-HEPE, and 6 keto-PGF1α, compared with the NK group. Besides, KEGG enrichment analysis also revealed the important metabolic pathways, such as linoleic acid metabolism, Biosynthesis of unsaturated fatty acids, and α-linolenic acid metabolism, were related to fatty acid metabolism. These results suggested that CGT could regulate the lipid metabolism in the liver of hyperlipidemia mice, and may regulate 54 potential biomarkers in mice through a related metabolic pathway to make them return to a normal state and improve the disorder of lipid metabolism.

Ganoderic acids-rich ethanol extract from Ganoderma lucidum protects against alcoholic liver injury and modulates intestinal microbiota in mice with excessive alcohol intake

Alcoholic liver injury is mainly caused by excessive alcohol consumption and has become a global public health problem threatening human health. It is well known that Ganoderma lucidum possesses various excellent beneficial effects on liver function and lipid metabolism. The purpose of this study was to evaluate the underlying protective effect and action mechanism of ganoderic acids-rich G. lucidum ethanol extract (GLE) on alcohol-induced liver injury in mice with excessive alcohol intake. Results showed that oral administration of GLE could obviously inhibit the abnormal increases of serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and also significantly protect the liver against alcohol-induced excessive hepatic lipid accumulation and pathological changes. In addition, alcohol-induced oxidative stress in liver was significantly ameliorated by the dietary intervention of GLE through reducing the hepatic levels of maleic dialdehyde (MDA) and lactate dehydrogenase (LDH), and increasing the hepatic levels of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and alcohol dehydrogenase (ADH). Compared with the model group, GLE intervention significantly ameliorated the intestinal microbial disorder by elevating the relative abundance of Ruminiclostridium_9, Prevotellaceae_UCG-001, Oscillibacter, [Eubacterium]_xylanophilum_group, norank_f_Clostridiates_vadinBB60_group, GCA-900066225, Bilophila, Ruminococcaceae_UCG-009, norank_f_Desulfovibrionaceae and Hydrogenoanaerobacterium, but decreasing the proportion of Clostridium_sensu_stricto_1. Furthermore, liver metabolomic profiling suggested that GLE intervention had a significant regulatory effect on the composition of liver metabolites in mice with excessive alcohol intake, especially the levels of some biomarkers involved in primary bile acid biosynthesis, riboflavin metabolism, tryptophan metabolism, biosynthesis of unsaturated fatty acids, fructose and mannose metabolism, glycolysis/gluconeogenesis. Additionally, dietary supplementation with GLE significantly regulated the mRNA levels of key genes related to fatty acids metabolism, ethanol catabolism and inflammatory response in liver. Conclusively, these findings indicate that GLE has a potentially beneficial effect on alleviating alcohol-induced liver injury and may be developed as a promising functional food ingredient.

Bacillus amyloliquefaciens SN16-1-Induced Resistance System of the Tomato against Rhizoctonia solani.

Tomato (Solanum lycopersicum), as an important economical vegetable, is often infected with Rhizoctonia solani, which results in a substantial reduction in production. Therefore, the molecular mechanism of biocontrol microorganisms assisting tomato to resist pathogens is worth exploring. Here, we use Bacillus amyloliquefaciens SN16-1 as biocontrol bacteria, and employed RNA-Seq technology to study tomato gene and defense-signaling pathways expression. Gene Ontology (GO) analyses showed that an oxidation-reduction process, peptidase regulator activity, and oxidoreductase activity were predominant. Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that phenylpropanoid biosynthesis, biosynthesis of unsaturated fatty acids, aldosterone synthesis and secretion, and phototransduction were significantly enriched. SN16-1 activated defenses in the tomato via systemic-acquired resistance (which depends on the salicylic acid signaling pathway), rather than classic induction of systemic resistance. The genes induced by SN16-1 included transcription factors, plant hormones (ethylene, auxin, abscisic acid, and gibberellin), receptor-like kinases, heat shock proteins, and defense proteins. SN16-1 rarely activated pathogenesis-related proteins, but most pathogenesis-related proteins were induced in the presence of the pathogens. In addition, the molecular mechanisms of the response of tomatoes to SN16-1 and R. solani RS520 were significantly different.

Resolvin E1-ChemR23 Axis Regulates the Hepatic Metabolic and Inflammatory Transcriptional Landscape in Obesity at the Whole Genome and Exon Level.

Resolvin E1 (RvE1) is an immunoresolvent that is synthesized from eicosapentaenoic acid and can bind the receptor ERV1/ChemR23. We previously showed activation of the RvE1-ChemR23 axis improves hyperglycemia and hyperinsulinemia of obese mice; however, it remains unclear how RvE1 controls glucose homeostasis. Here we investigated hepatic metabolic and inflammatory transcriptional targets of the RvE1-ChemR23 axis using lean and obese wild type (WT) and ChemR23 knockout (KO) mice. We conducted an in-depth transcriptional study by preforming whole gene-level and exon-level analyses, which provide insight into alternative splicing variants and miRNA regulation. Compared to controls, WT and KO obese mice in the absence of RvE1 displayed similar gene-level profiles, which entailed dysregulated pathways related to glucose homeostasis. Notably, obese WT mice relative to lean controls showed a robust decrease in pathways related to the biosynthesis of unsaturated fatty acids. At the exon-level, obese ChemR23 KOs compared to obese WT mice displayed changes in pathways related to hepatic lipid transport, cholesterol metabolism, and immunological functions such as complement cascades and platelet activation. Importantly, upon RvE1 administration to WT obese mice, we discovered upregulated genes in pathways relating to insulin sensitivity and downregulated genes related to regulators of TGF-β signaling. This transcriptional profile was generally not recapitulated with obese ChemR23 KO mice administered RvE1. Collectively, gene and exon-level analyses suggest RvE1 controls the hepatic transcriptional profile related to glucose homeostasis, insulin sensitivity, and inflammation in a manner that is largely dependent on ChemR23. These studies will drive future mechanistic experiments on the RvE1-ChemR23 axis.

Yeast β-Glucan Altered Intestinal Microbiome and Metabolome in Older Hens.

The prebiotics- and probiotics-mediated positive modulation of the gut microbiota composition is considered a useful approach to improve gut health and food safety in chickens. This study explored the effects of yeast β-glucan (YG) supplementation on intestinal microbiome and metabolites profiles as well as mucosal immunity in older hens. A total of 256 43-week-old hens were randomly assigned to two treatments, with 0 and 200 mg/kg of YG. Results revealed YG-induced downregulation of toll-like receptors (TLRs) and cytokine gene expression in the ileum without any effect on the intestinal barrier. 16S rRNA analysis claimed that YG altered α- and β-diversity and enriched the relative abundance of class Bacilli, orders Lactobacillales and Enterobacteriales, families Lactobacillaceae and Enterobacteriaceae, genera Lactobacillus and Escherichia–Shigella, and species uncultured bacterium-Lactobacillus. Significant downregulation of cutin and suberin, wax biosynthesis, atrazine degradation, vitamin B6 metabolism, phosphotransferase system (PTS), steroid degradation, biosynthesis of unsaturated fatty acids, aminobenzoate degradation and quorum sensing and upregulation of ascorbate and aldarate metabolism, C5-branched dibasic acid metabolism, glyoxylate and dicarboxylate metabolism, pentose and glucuronate interconversions, steroid biosynthesis, carotenoid biosynthesis, porphyrin and chlorophyll metabolism, sesquiterpenoid and triterpenoid biosynthesis, lysine degradation, and ubiquinone and other terpenoid-quinone biosyntheses were observed in YG-treated hens, as substantiated by the findings of untargeted metabolomics analysis. Overall, YG manifests prebiotic properties by altering gut microbiome and metabolite profiles and can downregulate the intestinal mucosal immune response of breeder hens.

Untargeted serum metabolomics and potential biomarkers for Sjögren's syndrome.

At present, the pathogenesis of Sjögren's syndrome (SS) remains unclear. This research aimed to identify differential metabolites that contribute to SS diagnosis and discover the disturbed metabolic pathways. Recent advances in mass spectrometry have allowed the identification of hundreds of unique metabolic signatures and the exploration of altered metabolite profiles in disease. In this study, 505 candidates including healthy controls (HCs) and SS patients were recruited and the serum samples were collected. A non-targeted gas chromatography-mass spectrometry (GC-MS) serum metabolomics method was used to explore the changes in serum metabolites. We found SS patients and HCs can be distinguished by 21 significant metabolites. The levels of alanine, tryptophan, glycolic acid, pelargonic acid, cis-1-2-dihydro-1-2-naphthalenediol, diglycerol, capric acid, turanose, behenic acid, dehydroabietic acid, stearic acid, linoleic acid, heptadecanoic acid, valine, and lactic acid were increased in serum samples from SS patients, whereas levels of catechol, anabasine, 3-6-anhydro-D-galactose, beta-gentiobiose, 2-ketoisocaproic acid and ethanolamine were decreased. The significantly changed pathways included the following: Linoleic acid metabolism; unsaturated fatty acid biosynthesis; aminoacyl-tRNA biosynthesis; valine, leucine, and isoleucine biosynthesis; glycerolipid metabolism; selenocompound metabolism; galactose metabolism; alanine, aspartate and glutamate metabolism; glyoxylate and dicarboxylate metabolism; glycerophospholipid metabolism; and valine, leucine and isoleucine degradation. These findings enhance the informative capacity of biochemical analyses through the identification of serum biomarkers and the analysis of metabolic pathways and contribute to an improved understanding of the pathogenesis of SS.

Fecal metabolomic analysis of rabbits infected with Eimeria intestinalis and Eimeria magna based on LC-MS/MS technique

Rabbit coccidiosis is a common parasitic disease leading to economic losses in the rabbit industry. The intestinal flora plays a key role in pathogenesis of coccidiosis, and fecal metabolome mediates host-microbiome interactions as a functional readout of the gut microbiome. In this study, the E. intestinalis-infected and E. magna-infected rabbit models were established to investigate metabolic alterations and metabolic pathways based on LC-MS/MS technique for the first time. Multivariate OPLS-DA analysis was performed to explore differential metabolites. In total, 288 metabolites were detected from infected and uninfected rabbits. The level of 33 metabolites increased and 4 decreased in rabbits infected with E. intestinalis. Eight pathways were significantly perturbed during E. intestinalis infection including biosynthesis of unsaturated fatty acids, fatty acid biosynthesis, etc. After rabbits infected with E. magna, 13 metabolites were altered and 7 metabolic pathways were dysregulated. These metabolites and metabolic pathways were mainly involved in tuberculosis, parathyroid hormone synthesis, etc. Besides, 25 metabolites differed in abundance between E. intestinalis infection group and E. magna infection group, the major perturbed metabolic pathways were lipid metabolism and endocrine system, respectively. In general, it is confirmed that E. intestinalis and E. magna infection destroyed the intestinal flora, which caused corresponding changes in metabolites, and provide novel insights into the molecular mechanisms of rabbit-parasite interactions.

Chromosome-Level Genome Assembly and HazelOmics Database Construction Provides Insights Into Unsaturated Fatty Acid Synthesis and Cold Resistance in Hazelnut (Corylus heterophylla).

Corylus heterophylla (2n = 22) is the most widely distributed, unique, and economically important nut species in China. Chromosome-level genomes of C. avellana, C. heterophylla, and C. mandshurica have been published in 2021, but a satisfactory hazelnut genome database is absent. Northeast China is the main distribution and cultivation area of C. heterophylla, and the mechanism underlying the adaptation of C. heterophylla to extremely low temperature in this area remains unclear. Using single-molecule real-time sequencing and the chromosomal conformational capture (Hi-C) assisted genome assembly strategy, we obtained a high-quality chromosome-scale genome sequence of C. heterophylla, with a total length of 343 Mb and scaffold N50 of 32.88 Mb. A total of 94.72% of the test genes from the assembled genome could be aligned to the Embryophyta_odb9 database. In total, 22,319 protein-coding genes were predicted, and 21,056 (94.34%) were annotated in the assembled genome. A HazelOmics online database (HOD) containing the assembled genome, gene-coding sequences, protein sequences, and various types of annotation information was constructed. This database has a user-friendly and straightforward interface. In total, 439 contracted genes and 3,810 expanded genes were identified through genome evolution analysis, and 17 expanded genes were significantly enriched in the unsaturated fatty acid biosynthesis pathway (ko01040). Transcriptome analysis results showed that FAD (Cor0058010.1), SAD (Cor0141290.1), and KAT (Cor0122500.1) with high expression abundance were upregulated at the ovule maturity stage. We deduced that the expansion of these genes may promote high unsaturated fatty acid content in the kernels and improve the adaptability of C. heterophylla to the cold climate of Northeast China. The reference genome and database will be beneficial for future molecular breeding and gene function studies in this nut species, as well as for evolutionary research on species of the order Fagales.

Multi-omics analysis reveals specific modifications associated with reduced chilling injury in bell pepper fruit by methyl jamonate

Bell pepper is prone to chilling injury during cold storage. In this study, the plant hormone, methyl jasmonate (MeJA), which can stimulate the expression of plant defense genes, was used to investigate its effects on the transcriptome, metabolome and proteome after 6 days at 4 ℃. Differentially expressed (DE) mRNAs that were identified with plant hormone signaling included the transcription factor MYC2, and those associated with antioxidant properties, membrane lipids and cell wall modification, fruit quality and an important transcription factors pathway -- calmodulin-binding transcription activator - c-repeat-binding factor - transcription factor ICE1 (CMAT-CaCBF1A-ICE1). Effects on the proteome analysis were mainly associated with glutathione metabolism, biosynthesis of unsaturated fatty acids and fatty acid metabolism. Differentially expressed metabolites were identified as acids, phenolics, and capsaicin. Our study suggests that MeJA treatment mitigates chilling injury of bell peppers though inhibiting the MYC2-JA signaling pathway, enhancing the ASA-GSH cycle, reducing membrane lipid damage, suppressing cell wall disassembly, and activating the CMAT-CBF-ICE pathway. These results provide a theoretical basis for further study on chilling injury of bell pepper fruit.

Microcystin-leucine arginine exposure induced intestinal lipid accumulation and MC-LR efflux disorder in Lithobates catesbeianus tadpoles

Few studies exist on the toxic effects of chronic exposure to microcystins (MCs) on amphibian intestines, and the toxicity mechanisms are unclear. Here, we evaluated the impact of subchronic exposure (30 days) to environmentally realistic microcystin-leucine arginine (MC-LR) concentrations (0 μg/L, 0.5 μg/L and 2 μg/L) on tadpole (Lithobates catesbeianus) intestines by analyzing the histopathological and subcellular microstructural damage, the antioxidative and oxidative enzyme activities, and the transcriptome levels. Histopathological results showed severe damage accompanied by inflammation to the intestinal tissues as the MC-LR exposure concentration increased from 0.5 μg/L to 2 μg/L. RNA-sequencing analysis identified 634 and 1,147 differentially expressed genes (DEGs) after exposure to 0.5 μg/L and 2 μg/L MC-LR, respectively, compared with those of the control group (0 μg/L). Biosynthesis of unsaturated fatty acids and the peroxisome proliferator-activated receptor (PPAR) signaling pathway were upregulated in the intestinal tissues of the exposed groups, with many lipid droplets being observed on transmission electron microscopy, implying that MC-LR may induce lipid accumulation in frog intestines. Moreover, 2 μg/L of MC-LR exposure inhibited the xenobiotic and toxicant biodegradation related to detoxification, implying that the tadpoles’ intestinal detoxification ability was weakened after exposure to 2 μg/L MC-LR, which may aggravate intestinal toxicity. Lipid accumulation and toxin efflux disorder may be caused by MC-LR-induced endoplasmic reticular stress. This study presents new evidence that MC-LR harms amphibians by impairing intestinal lipid metabolism and toxin efflux, providing a theoretical basis for evaluating the health risks of MC-LR to amphibians.

In situ Metabolomics of Metabolic Reprogramming Involved in a Mouse Model of Type 2 Diabetic Kidney Disease.

The in situ metabolic profiling of the kidney is crucial to investigate the complex metabolic reprogramming underlying diabetic kidney disease (DKD) and to allow exploration of potential metabolic targets to improve kidney function. However, as the kidney is a highly heterogeneous organ, traditional metabolomic methods based on bulk analysis that produce an averaged measurement are inadequate. Herein, we employed an in situ metabolomics approach to discover alternations of DKD-associated metabolites and metabolic pathways. A series of histology-specific metabolic disturbances were discovered in situ using airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI–MSI). In combination with integrated metabolomics analysis, five dysfunctional metabolic pathways were identified and located in the kidneys of type-2 DKD mice simultaneously for the first time, including taurine metabolism, arginine and proline metabolism, histidine metabolism, biosynthesis of unsaturated fatty acids, and fatty acid degradation pathways. As crucial nodes of metabolic pathways, five dysregulated rate-limiting enzymes related to altered metabolic pathways were further identified. These findings reveal alternations from metabolites to enzymes at the molecular level in the progression of DKD and provide insights into DKD-associated metabolic reprogramming.

Helicobacter pylori FabX contains a [4Fe-4S] cluster essential for unsaturated fatty acid synthesis

Unsaturated fatty acids (UFAs) are essential for functional membrane phospholipids in most bacteria. The bifunctional dehydrogenase/isomerase FabX is an essential UFA biosynthesis enzyme in the widespread human pathogen Helicobacter pylori, a bacterium etiologically related to 95% of gastric cancers. Here, we present the crystal structures of FabX alone and in complexes with an octanoyl-acyl carrier protein (ACP) substrate or with holo-ACP. FabX belongs to the nitronate monooxygenase (NMO) flavoprotein family but contains an atypical [4Fe-4S] cluster absent in all other family members characterized to date. FabX binds ACP via its positively charged α7 helix that interacts with the negatively charged α2 and α3 helices of ACP. We demonstrate that the [4Fe-4S] cluster potentiates FMN oxidation during dehydrogenase catalysis, generating superoxide from an oxygen molecule that is locked in an oxyanion hole between the FMN and the active site residue His182. Both the [4Fe-4S] and FMN cofactors are essential for UFA synthesis, and the superoxide is subsequently excreted by H. pylori as a major resource of peroxide which may contribute to its pathogenic function in the corrosion of gastric mucosa.

Placental metabolic profiling in gestational diabetes mellitus: An important role of fatty acids.

AimGestational diabetes mellitus (GDM) is the most common metabolic disorder during pregnancy. Accumulating studies have reported metabolites that are significantly associated with the development of GDM. However, studies on the metabolism of placenta, the most important organ of maternal‐fetal energy and material transport, are extremely rare. This study aimed to identify and discuss the relationship between differentially expressed metabolites (DEM) and clinical parameters of the mothers and newborns.MethodsIn this study, metabolites from 63 placenta tissues (32 GDM and 31 normal controls) were assayed by ultra‐performance liquid chromatography‐high resolution mass spectrometry (UPLC‐HRMS).ResultsA total of 1297 annotated metabolites were detected, of which 87 significantly different in GDM placenta. Lipids and lipid‐like molecules accounted for 62.1% of DEM as they were significantly enriched via the “biosynthesis of unsaturated fatty acids” and “fatty acid biosynthesis” pathways. Linoleic acid and α‐linolenic acid appeared to be good biomarkers for the prediction and diagnosis of GDM. In addition, the level of PC(14:0/18:0) was negatively correlated with neonatal weight. 14 metabolites significantly different in male and female offspring, with the most increase in female newborns.ConclusionEven if maternal blood glucose level is well controlled, there are still metabolic abnormalities in GDM. Lipids and lipid‐like molecules were the main differential metabolites, especially unsaturated fatty acids.

Effect of an Established Nutritional Level of Selenium on Energy Metabolism and Gene Expression in the Liver of Rainbow Trout.

The nutritional selenium (Se) has been demonstrated to have health-boosting effects on fish. However, its effect on fish energy metabolism remains unclear. This study explores the effect and underlying mechanism of the action of nutritional Se on energy metabolism in fish. Rainbow trout (Oncorhynchus mykiss) were fed a basal diet (0mg Se/kg diet) and a diet containing an already established nutritional Se level (2mg Se/kg diet, based on Se-yeast) for 30days. After the feeding experiment, the plasma and liver biochemical profiles and liver transcriptome were analyzed. The results showed that the present nutritional level of Se significantly increased liver triglyceride, total cholesterol, and plasma total cholesterol contents (P < 0.05) compared with the control. Transcriptome analysis showed that 336 and 219 genes were significantly upregulated and downregulated, respectively. Gene enrichment analysis showed that many differentially expressed genes (DEGs) were associated with lipid metabolism pathways (fatty acid biosynthesis, fatty acid elongation, and unsaturated fatty acid biosynthesis), carbohydrate metabolism pathways (glycolysis, the pentose phosphate pathway, and the citrate cycle), and the oxidative phosphorylation pathway. Real-time quantitative PCR (Q-PCR) validation results showed that the expression profiles of 15 genes exhibited similar trends both in RNA sequencing (RNA-seq) and Q-PCR analysis. These results reveal that optimum dietary Se activates glucose catabolic processes, fatty acid biosynthetic processes, and energy production and hence produces higher liver lipid content. This study concludes that the previously established level of nutritional Se (Se-yeast) (2mg/kg diet, fed basis) for rainbow trout promotes energy storage in the liver, which may benefit fish growth to some extent.

Identifying the cardioprotective mechanism of Danyu Tongmai Granules against myocardial infarction by targeted metabolomics combined with network pharmacology

BackgroundDanyu Tongmai Granules (DY), the commercial Chinese medicine, was well-accepted cardiovascular protective actions in clinic. However, the mechanisms underlying the beneficial effects of DY on cardiovascular disease still need largely to be clarified. PurposeTherefore, this study was designed to explore potential mechanisms of DY in myocardial infarction (MI) by integrated strategy of metabolomics and network pharmacology. MethodsCardiomyocytes were subjected to H2O2 induced myocardial injury and rats were induced MI via isoproterenol (ISO) injection. The entire metabolic alterations in serum and heart tissues of experimental rats were profiled by UPLC-MS/MS. Based on the identified differential metabolites, the pathway analysis results were obtained and further validated using the network pharmacology approach. ResultsWe found that DY exerted significant cardioprotective effects in vitro and in vivo, and ameliorated inflammatory cell infiltration and cardiomyocyte apoptosis induced by ISO. The metabolomics data suggested that DY mainly affected the amino acid metabolism (i.e., valine, leucine and isoleucine biosynthesis, arginine biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, arginine biosynthesis, glycine, serine, as well as the alanine metabolism, aspartate and glutamate metabolism, etc.). Simultaneously, DY participated in the regulation of the biosynthesis of bile acids and biosynthesis of unsaturated fatty acids. Notably, DY significantly reduced the biosynthesis of valine, leucine and isoleucine to regulating the metabolism of branched chain amino acids (BCAAs) in infarcted myocardium, thus blocking the inflammation via inhibiting the expression of NLRP3 inflammasome in ISO-induced rats. The anti-inflammatory system of DY was further validated with the results of network pharmacology. ConclusionOur study, for the first time, confirmed that DY inhibited inflammation and further exerted significant anti-myocardial infarction effect. Additionally, our work further demonstrated that the myocardial protective effect of DY was contributed to the inhibition of the NLRP3 inflammasome activation by regulating BCAAs in infarcted myocardium using the comprehensive metabolomics, molecular biology and network analysis. Overall, our study gained new insights into the role of the relationship between the metabolic regulation of BCAAs and the NLRP3 inflammasome against MI.