Search Results (33)

Neonicotinoid resistance is increasingly prevalent in the agricultural pest Myzus persicae. Lipids play a critical role in insect defense systems, but their contribution to insect neonicotinoid resistance is disregarded. We conducted metabolomics and transcriptomics studies on M. persicae thiacloprid-resistant (THG-R) and -susceptible (FFJ-S) populations. A total of 149 lipid metabolites were identified, with 90 upregulated and 59 downregulated in THG-R compared to in FFJ-S. Metabolites in the arachidonic acid (AA) pathway substantially varied between THG-R and FFJ-S. For example, arachidonic acid, (±)11-HETE, and prostaglandin B1 were significantly upregulated, while prostaglandin A1, tetranor-PGDM, 8,15-diHETE, and (±)11(12)-EET were significantly decreased in THG-R. Transcriptomics profiles and qPCR indicated that lipid metabolic enzymes, including fatty acid synthase (FAS), the elongase of very-long-chain fatty acids (ELO), fatty acid desaturase (FAD), and phospholipase (PL) genes, were not overexpressed in THG-R. Among the twelve thioesterase genes, only MpTHEM6a was significantly upregulated in THG-R. Knocking down the expression of MpTHEM6a in THG-R significantly increased the toxicity of the three neonicotinoids, reduced the lifespan of adults, and decreased the number of nonviable nymphs produced by female adults. The metabolites AA, (±)11-HETE, and prostaglandin B1 are potential biomarkers in neonicotinoid-resistant M. persicae. MpTHEM6a may become a potential target for combating neonicotinoid-resistant M. persicae. Full article

Elongases of very-long-chain fatty acids (Elovls) are critical rate-limiting enzymes that are involved in LC-PUFA biosynthesis through catalyzing the two-carbon elongation of a pre-existing fatty acyl chain. Thus far, several Elovls have been extensively studied in teleost. However, the functional and physiological roles of Elovls in chondrichthyans have rarely been reported. In this study, we identified and characterized elovl2 from the endangered Chinese sturgeon (Acipenser sinensis) by whole genome scanning. The results show that the coding sequence of elovl2 was 894 bp in length, for a putative protein of 297 amnio acids. Comparative genomic analyses indicated that Chinese sturgeon elovl2 was evolutionarily conserved. Functional characterization in yeast demonstrated that the Chinese sturgeon Elovl2 could efficiently elongate C₂₀ (ARA and EPA) and C₂₂ (22:4n-6 and 22:5n-3) substrates, confirming its critical roles in LC-PUFA biosynthesis. Spatial and temporal expression analyses showed high elovl2 mRNA levels were detected in the liver and brain and showed an increase trend both in embryonic and post-hatching stages. Interestingly, diets with vegetable oils as lipid sources could significantly induce the high expression of elovl2 in Chinese sturgeon, implying that the endogenous LC-PUFA biosynthesis pathway was stimulated by lack of LC-PUFA in their diets. Our findings will enhance our understanding about the evolutionary and functional roles of elovl2 and provide novel insights into the LC-PUFA biosynthesis mechanism in vertebrates. Full article

Castration is commonly used to reduce stink during boar production. In porcine adipose tissue, castration reduces androgen levels resulting in metabolic disorders and excessive fat deposition. However, the underlying detailed mechanism remains unclear. In this study, we constructed porcine preadipocyte models with and without androgen by adding testosterone exogenously. The fluorescence intensity of lipid droplet (LD) staining and the fatty acid synthetase (FASN) mRNA levels were lower in the testosterone-treated cells than in the untreated control cells. In contrast, the mRNA levels of adipose triglycerides lipase (ATGL) and androgen receptor (AR) were higher than in the testosterone-treated cells than in the control cells. Subsequently, transcriptomic sequencing of porcine preadipocytes incubated with and without testosterone showed that the mRNA expression levels of very long-chain fatty acid elongase 3 (ELOVL3), a key enzyme involved in fatty acids synthesis and metabolism, were high in control cells. The siRNA-mediated knockdown of ELOVL3 reduced LD accumulation and the mRNA levels of FASN and increased the mRNA levels of ATGL. Next, we conducted dual-luciferase reporter assays using wild-type and mutant ELOVL3 promoter reporters, which showed that the ELOVL3 promoter contained an androgen response element (ARE); furthermore, its transcription was negatively regulated by AR overexpression. In conclusion, our study reveals that testosterone inhibits fat deposition in porcine preadipocytes by suppressing ELOVL3 expression. Moreover, our study provides a theoretical basis for further studies on the mechanisms of fat deposition caused by castration. Full article

Disordered eating behavior differs between the restricting subtype (AN-R) and the binging and purging subtype (AN-BP) of anorexia nervosa (AN). Yet, little is known about how these differences impact fatty acid (FA) dysregulation in AN. To address this question, we analyzed 26 FAs and 7 FA lipogenic enzymes (4 desaturases and 3 elongases) in 96 women: 25 AN-R, 25 AN-BP, and 46 healthy control women. Our goal was to assess subtype-specific patterns. Lauric acid was significantly higher in AN-BP than in AN-R at the fasting timepoint (p = 0.038) and displayed significantly different postprandial changes 2 h after eating. AN-R displayed significantly higher levels of n-3 alpha-linolenic acid, stearidonic acid, eicosapentaenoic acid (EPA), docosapentaenoic acid, and n-6 linoleic acid and gamma-linolenic acid compared to controls. AN-BP showed elevated EPA and saturated lauric acid compared to controls. Higher EPA was associated with elevated anxiety in AN-R (p = 0.035) but was linked to lower anxiety in AN-BP (p = 0.043). These findings suggest distinct disordered eating behaviors in AN subtypes contribute to lipid dysregulation and eating disorder comorbidities. A personalized dietary intervention may improve lipid dysregulation and enhance treatment effectiveness for AN. Full article

Ectropis obliqua, a notorious tea pest, produces a Type-II sex pheromone blend for mate communication. This blend contains (Z,Z,Z)-3,6,9-octadecatriene, (Z,Z)-3,9-cis-6,7-epoxy-octadecadiene, and (Z,Z)-3,9-cis-6,7-epoxy-nonadecadiene. To elucidate the genes related to the biosynthesis of these sex pheromone components, transcriptome sequencing of the female E. obliqua pheromone gland and the abdomen without pheromone gland was performed. Comparative RNAseq analyses identified 52 putative genes, including 7 fatty acyl-CoA elongases (ELOs), 9 fatty acyl-CoA reductases (FARs), 1 decarbonylase (DEC), 3 lipophorins (LIPs), and 32 cytochrome P450 enzymes (CYPs). Tissue expression profiles revealed that two ELOs (ELO3 and ELO5), two FARs (FAR2 and FAR9), one DEC (CYP4G173), and one LIP (LIP1) displayed either abdomen-centric or -specific expression, suggesting potential roles in sex pheromone biosynthesis within the oenocytes of E. obliqua. Furthermore, the tissue expression patterns, combined with phylogenetic analysis, showed that CYP340BD1, which was expressed specifically and predominantly only in the pheromone gland, was clustered with the previously reported epoxidases, highlighting its potential role in the epoxidation of the unsaturated polytriene sex pheromone components. Collectively, our research provides valuable insights into the genes linked to sex pheromone biosynthesis. Full article

Docosahexaenoic acid (DHA) is an essential nutrient for humans and plays a critical role in human development and health. Freshwater fish, such as the common carp (Cyprinus carpio), have a certain degree of DHA biosynthesis ability and could be a supplemental source of human DHA needs. The elongase of very-long-chain fatty acid 5 (Elovl5) is an important enzyme affecting polyunsaturated fatty acid (PUFA) biosynthesis. However, the function and regulatory mechanism of the elovl5 gene related to DHA synthesis in freshwater fish is not clear yet. Previous studies have found that there are two copies of the elovl5 gene, elovl5a and elovl5b, which have different functions. Our research group found significant DHA content differences among individuals in Yellow River carp (Cyprinus carpio var.), and four candidate genes were found to be related to DHA synthesis through screening. In this study, the expression level of elovl5a is decreased in the high-DHA group compared to the low-DHA group, which indicated the down-regulation of elovl5a in the DHA synthesis pathways of Yellow River carp. In addition, using a dual-luciferase reporter gene assay, we found that by targeting the 3’UTR region of elovl5a, miR-26a-5p could regulate DHA synthesis in common carp. After CRISPR/Cas9 disruption of elovl5a, the DHA content in the disrupted group was significantly higher than in the wildtype group; meanwhile, the expression level of elovl5a in the disrupted group was significantly reduced compared with the wildtype group. These results suggest that elovl5a may be down-regulating DHA synthesis in Yellow River carp. This study could provide useful information for future research on the genes and pathways that affect DHA synthesis. Full article

Fatty acid elongases play crucial roles in synthesizing long-chain polyunsaturated fatty acids. Identifying more efficient elongases is essential for enhancing oleaginous microorganisms to produce high yields of target products. We characterized three elongases that were identified with distinct specificities: McELO from Mucor circinelloides, PrELO from Phytophthora ramorum, and PsELO from Phytophthora sojae. Heterologous expression in Saccharomyces cerevisiae showed that McELO preferentially elongates C16 to C18 fatty acids, PrELO targets Δ6 polyunsaturated fatty acids, and PsELO uses long chain saturated fatty acids as substrates. McELO and PrELO exhibited more homology, potentially enabling fatty acid composition remodeling and enhanced LC-PUFAs production in oleaginous microorganisms. Site-directed mutagenesis of conserved amino acids across elongase types identified residues essential for activity, supported by molecular docking. Alanine substitution of conserved polar residues led to enzyme inactivation, underscoring their importance in the condensation reaction. Our findings offer promising elongase candidates for polyunsaturated fatty acid production, contributing to the bioindustry’s sustainable development. Full article

Background and objectives: Nutritional intake and dysregulation of fatty acid metabolism play a role in the progression of various tumours. The consumption of different fatty acids is difficult to assess accurately by dietary questionnaires. Biomarkers allow objective assessments of intake, storage, and bioavailability. We studied the association between the polyunsaturated fatty acid (PUFA) composition of abdominal subcutaneous adipose tissue (a good indicator of dietary intake over 2–3 years) and all-cause mortality. Methods: In this multicentre AGARIC study, including 203 patients with colorectal cancer (CRC) undergoing curative surgery, samples were harvested from subcutaneous adipose tissue, which were analysed for PUFA composition. Cox proportional hazards models were used to estimate associations between PUFA levels and mortality. Results: After a median follow-up of 45 months, 76 patients died. These patients were more often men (72.4% vs. 57.5%, p = 0.04), diabetic (32.9% vs. 13.4%, p = 0.001), older (median: 74.5 vs. 66.6 years, p = <0.001), and with high alcohol consumption (47.4% vs. 30.7%, p = 0.005) compared to survivors. An increased risk of death was observed with higher levels of eicosadienoic acid (hazard ratio tertile3 vs tertile1 (HRT3vsT1) = 2.12; 95% confidence interval (CI) = 1.01–4.42; p-trend = 0.04), adrenic acid (HRT3vsT1 = 3.52; 95% CI = 1.51–8.17; p-trend = 0.005), and 22:5 n-6 (HRT3vsT1 = 3.50; 95% CI = 1.56–7.87; p-trend = 0.002). Conversely, the risk of death seemed to be lower when higher concentrations of ү-linolenic acid (HRT3vsT1 = 0.52; 95% CI = 0.27–0.99; p-trend = 0.04) and the essential fatty acid α-linolenic acid (HRT3vsT1 = 0.47; 95% CI = 0.24–0.93; p-trend = 0.03) were observed. The estimated δ-6-desaturase & elongase 5 enzyme activity were found to be positively associated with all-cause mortality (HRT3vsT1 = 2.25; 95% CI = 1.03–4.90; p-trend = 0.04). Discussion: The risk of death in CRC patients was increased in those with higher concentrations of certain n-6 PUFAs and lower concentrations of α-linolenic acid in their subcutaneous adipose tissue. These results reflect both dietary habits and altered fatty acid metabolism. Nevertheless, our exploratory results need to be confirmed in larger studies with further exploration of the mechanisms involved. The AGARIC study group: Scherrer Marie-Lorraine (Regional Hospital Centre Metz Thionville), Ayav Ahmet (University hospital of Nancy), Ortega-Deballon Pablo, (University hospital of Dijon), Lakkis Zaher (University hospital of Besançon), Liu David (University hospital Hautepierre of Strasbourg), and Deguelte Sophie (University hospital of Reims). Full article

Flaxseed contains huge quantities of anti-nutritional factors (ANFs), which reduce the performance of livestock. Three different protease and multi-carbohydrase enzymes were included in wheat-flaxseed diets (WFD) and corn-flaxseed diets (CFD) to compare their effects on performance, egg n-3 deposition, and fatty acid transporter genes in laying hens. A total of 540, twenty-week-old, Nongda-3 laying hens (DW brown × Hy-line white) were randomly assigned to six dietary groups, including 10% WFD or 10% CFD plus (i) supplemental enzyme A (alkaline protease 40,000 and neutral protease 10,000 (U/g)), (ii) enzyme B (alkaline protease 40,000, neutral protease 10,000, and cellulase 4000 (U/g)), or iii) enzyme C (neutral protease 10,000, xylanase 35,000, β-mannanase 1500, β-glucanase 2000, cellulose 500, amylase 100, and pectinase 10,000 (U/g)). An interaction (p < 0.05) was found for egg mass, hen day of egg production, and feed conversion ratio on the 9–10th week of the experiment. The WFD with enzyme B was associated with the highest egg weight in the 9–10th week. The deposition of total n-3 was superior with WFD (468.22 mg/egg) compared to CFD (397.90 mg/egg), while addition of enzyme C (464.90 mg/egg) resulted in the deposition of more total n-3 compared to enzymes A and B (411.89 and 422.42 mg/egg). The WFD and enzyme C significantly (p < 0.001) enhanced docosahexaenoic acid (DHA) and reduced the n-6:n-3 ratio in egg yolk compared to the CFD. The hepatic mRNA expression of liver fatty acid binding protein (L-FABP) (p = 0.006), fatty acid desaturase 1 (FADS-1) (p < 0.001), elongase-2 (ELOV-2) (p < 0.001), fatty acid transport protein-1 (FATP1) (p < 0.001), and the intestinal mRNA expression of FATP and FABP genes were increased with WFD compared to CFD. In conclusion, WFD with enzyme C is favorable for optimal performance, results in the deposition of more n-3 and DHA, and increases the expression of fatty acid transporter genes, which helps in n-3 transport. Full article

One area of glioblastoma research is the metabolism of tumor cells and detecting differences between tumor and healthy brain tissue metabolism. Here, we review differences in fatty acid metabolism, with a particular focus on the biosynthesis of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA) by fatty acid synthase (FASN), elongases, and desaturases. We also describe the significance of individual fatty acids in glioblastoma tumorigenesis, as well as the importance of glycerophospholipid and triacylglycerol synthesis in this process. Specifically, we show the significance and function of various isoforms of glycerol-3-phosphate acyltransferases (GPAT), 1-acylglycerol-3-phosphate O-acyltransferases (AGPAT), lipins, as well as enzymes involved in the synthesis of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), and cardiolipin (CL). This review also highlights the involvement of diacylglycerol O-acyltransferase (DGAT) in triacylglycerol biosynthesis. Due to significant gaps in knowledge, the GEPIA database was utilized to demonstrate the significance of individual enzymes in glioblastoma tumorigenesis. Finally, we also describe the significance of lipid droplets in glioblastoma and the impact of fatty acid synthesis, particularly docosahexaenoic acid (DHA), on cell membrane fluidity and signal transduction from the epidermal growth factor receptor (EGFR). Full article

Circulating fatty acids (FA) have an endogenous or exogenous origin and are metabolized under the effect of many enzymes. They play crucial roles in many mechanisms: cell signaling, modulation of gene expression, etc., which leads to the hypothesis that their perturbation could be the cause of disease development. FA in erythrocytes and plasma rather than dietary FA could be used as a biomarker for many diseases. Cardiovascular disease was associated with elevated trans FA and decreased DHA and EPA. Increased arachidonic acid and decreased Docosahexaenoic Acids (DHA) were associated with Alzheimer’s disease. Low Arachidonic acid and DHA are associated with neonatal morbidities and mortality. Decreased saturated fatty acids (SFA), increased monounsaturated FA (MUFA) and polyunsaturated FA (PUFA) (C18:2 n-6 and C20:3 n-6) are associated with cancer. Additionally, genetic polymorphisms in genes coding for enzymes implicated in FA metabolism are associated with disease development. FA desaturase (FADS1 and FADS2) polymorphisms are associated with Alzheimer’s disease, Acute Coronary Syndrome, Autism spectrum disorder and obesity. Polymorphisms in FA elongase (ELOVL2) are associated with Alzheimer’s disease, Autism spectrum disorder and obesity. FA-binding protein polymorphism is associated with dyslipidemia, type 2 diabetes, metabolic syndrome, obesity, hypertension, non-alcoholic fatty liver disease, peripheral atherosclerosis combined with type 2 diabetes and polycystic ovary syndrome. Acetyl-coenzyme A carboxylase polymorphisms are associated with diabetes, obesity and diabetic nephropathy. FA profile and genetic variants of proteins implicated in FA metabolism could be considered as disease biomarkers and may help with the prevention and management of diseases. Full article

Omega-3 (ω-3) polyunsaturated fatty acids, including docosahexaenoic acid (DHA), are involved in numerous biological processes and have a range of health benefits. DHA is obtained through the action of elongases (ELOVLs) and desaturases, among which Elovl2 is the key enzyme involved in its synthesis, and can be further metabolized into several mediators that regulate the resolution of inflammation. Our group has recently reported that ELOVL2 deficient mice (Elovl2^−/−) not only display reduced DHA levels in several tissues, but they also have higher pro-inflammatory responses in the brain, including the activation of innate immune cells such as macrophages. However, whether impaired synthesis of DHA affects cells of adaptive immunity, i.e., T lymphocytes, is unexplored. Here we show that Elovl2^−/− mice have significantly higher lymphocytes in peripheral blood and that both CD8+ and CD4+ T cell subsets produce greater amounts of pro-inflammatory cytokines in both blood and spleen compared to wild type mice, with a higher percentage of cytotoxic CD8+ T cells (CTLs) as well as IFN-γ-producing Th1 and IL-17-producing Th17 CD4+ cells. Furthermore, we also found that DHA deficiency impacts the cross-talk between dendritic cells (DC) and T cells, inasmuch as mature DCs of Elovl2^−/− mice bear higher expression of activation markers (CD80, CD86 and MHC-II) and enhance the polarization of Th1 and Th17 cells. Reintroducing DHA back into the diets of Elovl2^−/− mice reversed the exacerbated immune responses observed in T cells. Hence, impairment of endogenous synthesis of DHA exacerbates T cell inflammatory responses, accounting for an important role of DHA in regulating adaptive immunity and in potentially counteracting T-cell-mediated chronic inflammation or autoimmunity. Full article

Most diploid freshwater and marine fish encode one elovl5 elongase, having substrate specificity and activities towards C18, C20 and C22 polyunsaturated fatty acids (PUFAs). The allo-tetraploid common carp is hypothesized to encode two duplicated elovl5 genes. How these two elovl5 genes adapt to coordinate the PUFA biosynthesis through elongase function and expression divergence requires elucidation. In this study, we obtained the full-length cDNA sequences of two elovl5 genes in common carp, named as elovl5a and elovl5b. Functional characterization showed that both enzymes had elongase activity towards C18, C20 and C22 PUFAs. Especially, the activities of these two enzymes towards C22 PUFAs ranged from 3.87% to 8.24%, higher than those in most freshwater and marine fish. The Elovl5a had higher elongase activities than Elovl5b towards seven substrates. The spatial-temporal expression showed that both genes co-transcribed in all tissues and development stages. However, the expression levels of elovl5b were significantly higher than those of elovl5a in all examined conditions, suggesting that elovl5b would be the dominantly expressed gene. These two genes had different potential transcriptional binding sites. These results revealed the complicated roles of elovl5 on PUFA synthesis in common carp. The data also increased the knowledge of co-ordination between two homoeologs of the polyploid fish through function and expression divergence. Full article

Very-long-chain fatty acids (VLCFA) are involved in a number of important plant physiological functions. Disorders in the expression of genes involved in the synthesis of VLCFA lead to a number of phenotypic consequences, ranging from growth retardation to the death of embryos. The elongation of VLCFA in the endoplasmic reticulum (ER) is carried out by multiple elongase complexes with different substrate specificities and adapted to the synthesis of a number of products required for a number of metabolic pathways. The information about the enzymes involved in the synthesis of VLCFA with more than 26 atoms of Carbon is rather poor. Recently, genes encoding enzymes involved in the synthesis of both regular-length fatty acids and VLCFA have been discovered and investigated. Polyunsaturated VLCFA in plants are formed mainly by 20:1 elongation into new monounsaturated acids, which are then imported into chloroplasts, where they are further desaturated. The formation of saturated VLCFA and their further transformation into a number of aliphatic compounds included in cuticular waxes and suberin require the coordinated activity of a large number of different enzymes. Full article

Elongases of very long-chain fatty acids (Elovls) and fatty acid desaturases (Fads) are crucial enzymes involved in the biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFAs). In this paper, we report the molecular cloning and characterization of three genes from the marine teleost Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂, and analyzed tissue distribution and their expression in response to dietary n-3 LC-PUFA levels after a 42-day feeding experiment. The elovl5, elovl8 and fads2 genes encoded 294, 263 and 445 amino acids, respectively, which exhibited all the characteristics of the Elovl and Fads family. Tissue distribution analysis revealed that elovl5, elovl8 and fads2 were widely transcribed in various tissues, with the highest level in the brain, as described in other carnivorous marine teleosts. The transcript levels of elovl5, elovl8 and fads2 in the liver were significantly affected by dietary n-3 LC-PUFA, and higher LC-PUFA levels repressed their expression. These results demonstrated, for the first time, the presence and nutritional modulation of elovl5, elovl8 and fads2 cDNA in the juvenile hybrid grouper. Further studies are needed to determine the functional characterization of these genes and explore the mechanism of these genes when regulated by dietary fatty lipid profiles in this species. Full article