Search Results (44)

Proteins for elongation of very long-chain fatty acids (ELOVLs) are critical for the synthesis of long-chain polyunsaturated fatty acids (LC-PUFAs), and they are one group of the rate-limiting enzymes responsible for the initial condensation reaction within the fatty acid elongation. Elovl8 is a newly identified member of the ELOVL protein family, and its evolutionary and functional characterizations are still rarely reported. Here, we identified two elovl8 paralogues (named Scelovl8 and Scelovl8b) from Chinese perch (Siniperca chuatsi), and then their molecular and evolutionary characteristics, as well as potential roles involved in LC-PUFA biosynthesis, were examined. The ORFs of both Scelovl8a and Scelovl8b genes were 810 bp and 789 bp in length, encoding proteins of 270 and 263 amino acids, respectively. Multiple protein sequence comparisons indicated that elovl8 genes were highly conserved in teleosts, showing similar structural function domains. Meanwhile, phylogenetic analysis showed that the elovl8 gene family was clustered into two subclades of elovl8a and elovl8b, and Scelovl8a and Scelovl8b shared close relationships with banded archerfish elovl8a and striped bass elovl8b, respectively. Genetic synteny and gene structure analyses further confirmed that elovl8b is more conserved in comparison to elovl8a in teleosts. In addition, Scelovl8a was found to be highly expressed in the liver, while Scelovl8b was most abundant in the gills. Long-term food deprivation and refeeding are verified to regulate the transcription of Scelovl8a and Scelovl8b, and intraperitoneal injection of fish oil (FO) and vegetable oil (VO) significantly modified their gene expression as well. In summary, our results in this study indicate that elovl8 genes were conservatively unique to teleosts, and both elovl8 genes might be involved in the endogenous biosynthesis of LC-PUFAs in Chinese perch. These findings not only expand our knowledge on the evolutionary and functional characteristics of both elovl8 genes but also lay a solid basis for investigating regulatory mechanisms of LC-PUFA biosynthesis in various teleosts. Full article

Endometrial cancer (EC) is a complex gynecologic malignancy that requires a deeper understanding of its molecular basis to improve therapeutic strategies. In this study, we investigated the role of fatty acid (FA) reprogramming in the progression of EC. We analyzed FA profiles to identify the stage-specific changes and gene expression profiles of key enzymes involved in FA synthesis, desaturation, elongation, transport, and oxidation at different stages of EC. Our results show that EC tissues have lower levels of saturated FA and branched-chain FA, higher levels of very long-chain FA, n-3 polyunsaturated FA (PUFA), and monounsaturated FA, with the exception of myristoleic acid. The differences in n-6 PUFA were inconsistent. Gene expression analysis revealed the upregulation of key enzymes controlling de novo FA synthesis, including ACACA, FASN, SCD1, and ELOVL1. In contrast, the expression of genes related to FA transport in the cell and β-oxidation was downregulated. The expression of some genes related to PUFA metabolism was upregulated, while others were downregulated. These results demonstrate a reprogramming of lipid metabolism in EC tissues and suggest potential targets for novel therapeutic interventions in EC. Full article

The impact of dietary lipid sources on nutrient metabolism and reproductive development is a critical focus in aquaculture broodstock nutrition. Previous studies have demonstrated that fish oil supplementation modulates the expression of genes involved in steroid hormone synthesis, glucose, and lipid metabolism promoting ovarian development in female Scatophagus argus (spotted scat). However, the effects of fish oil on hepatic function at the protein level remain poorly characterized. In this study, female S. argus were fed diets containing 8% fish oil (FO, experimental group) or 8% soybean oil (SO, control group) for 60 days. Comparative proteomic analysis of liver tissue identified significant differential protein expression between groups. The FO group exhibited upregulation of lipid metabolism-related proteins, including COMM domain-containing protein 1 (Commd1), tetraspanin 8 (Tspan8), myoglobin (Mb), transmembrane protein 41B (Tmem41b), stromal cell-derived factor 2-like protein 1 (Sdf2l1), and peroxisomal biogenesis factor 5 (Pex5). Additionally, glucose metabolism-associated proteins, such as Sdf2l1 and non-POU domain-containing octamer-binding protein (Nono), were elevated in the FO group. Moreover, proteins linked to inflammation and antioxidant responses, including G protein-coupled receptor 108 (Gpr108), protein tyrosine phosphatase non-receptor type 2 (Ptpn2), Pex5, p120 catenin (Ctnnd1), tripartite motif-containing protein 16 (Trim16), and aquaporin 11 (Aqp11), were elevated in the FO group, while proteins involved in oxidative stress, such as reactive oxygen species modulator 1 (Romo1), cathepsin A (Ctsa), and Cullin 4A (Cul4a), were downregulated. These proteomic findings align with prior transcriptomic data, indicating that dietary fish oil enhances hepatic lipid metabolism, mitigates oxidative stress, and strengthens antioxidant capacity. Furthermore, these hepatic adaptations may synergistically support ovarian maturation in S. argus. This study provides novel proteomic-level evidence supporting the role of fish oil in modulating hepatic lipid and energy metabolism, thereby elucidating the role of fish oil in optimizing hepatic energy metabolism and redox homeostasis to influence reproductive processes, advancing our understanding of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) in teleost liver physiology. Full article

Lipids form energy storage depots, cellular barriers and signaling molecules. They are generated and metabolized by enzymes under the influence of biotic and abiotic factors, and some—the long-chain polyunsaturated ω3 and ω6 fatty acids and cholesterol—are essential for optimal health in marine organisms. In addition, lipids have direct and indirect roles in the control of buoyancy in marine fauna ranging from copepods to whales. Phytoplankton account for about half of the planet’s carbon fixation, and about half of that carbon goes into lipids. Lipids are an important component of the ocean’s ability to sequester carbon away from the atmosphere through sinking and especially after transfer to zooplankton. Phytoplankton are the main suppliers of ω3 polyunsaturated fatty acids (PUFAs) in the marine environment. They also supply cholesterol and many phytosterols to ocean ecosystems; however, genomics is indicating that members of the Cnidaria, Rotifera, Annelida, and Mollusca phyla also have the endogenous capacity for the de novo synthesis of ω3 PUFAs as well as phytosterols. It has been predicted that ω3 long-chain PUFAs will decrease in marine organisms with climate change, with implications for human consumption and for carbon sequestration; however, the responses of ω3 PUFA supply to future conditions are likely to be quite diverse. Full article

In mammals, fatty acid transport protein 1 (FATP1) plays important roles in cellular uptake and activation of long-chain fatty acid (LCFA), especially in processes of transportation, oxidation and triacylglycerol synthesis. However, the role of FATP1 in invertebrates, especially decapod crustaceans, is still poorly understood. In this study, the cDNA of a FATP1 gene from a decapod crustacean, mud crab Scylla paramamosain, was cloned and functionally characterized. The FATP1 gene encoded a polypeptide consisting of 643 amino acids that exhibits all the typical features of the FATP family and shares high homology with the other FATP orthologs of crustaceans. The relative mRNA expression levels of FATP1 were observed to be higher in metabolically active tissues such as hepatopancreas, stomach and gill than in other crab parts. Knockdown of the FATP1 mRNA in vivo significantly reduced triacylglycerols and total lipid levels in the hepatopancreas, accompanied by an increase in the expression of genes related to fatty acid transportation, allocation and hydrolysis, including long-chain acyl-CoA synthetase 3/4 (ACSL3/4) and carnitine palmitoyl transferase 1 (CPT1), and a decrease in the expression of genes related to fatty acid synthesis such as acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) in the hepatopancreas. Furthermore, increased dietary n-3 long-chain polyunsaturated fatty acid (LC-PUFA) levels resulted in the up-regulation of the FATP1 expression in the hepatopancreas, accompanied by an increase in LC-PUFA content, especially eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), in both polar (PLs) and neutral lipids (NLs) in the hepatopancreas and muscles of crabs. These findings suggested that the FATP1 gene identified in S. paramamosain might play important roles in regulating long-chain fatty acid metabolism and deposition in crustaceans. Full article

Aurantiochytrium is a well-known long-chain polyunsaturated fatty acids (PUFAs) producer, especially docosahexaenoic acid (DHA). In order to reduce the cost or improve the productivity of DHA, many researchers are focusing on exploring the high-yield strain, reducing production costs, changing culture conditions, and other measures. In this study, DHA production was improved by a two-stage fermentation. In the first stage, efficient and cheap soybean powder was used instead of conventional peptone, and the optimization of fermentation conditions (optimal fermentation conditions: temperature 28.7 °C, salinity 10.7‰, nitrogen source concentration 1.01 g/L, and two-nitrogen ratio of yeast extract to soybean powder 2:1) based on response surface methodology resulted in a 1.68-fold increase in biomass concentration. In the second stage, the addition of 2.5 mM sesamol increased the production of fatty acid and DHA by 93.49% and 98.22%, respectively, as compared to the optimal culture condition with unadded sesamol. Transcriptome analyses revealed that the addition of sesamol resulted in the upregulation of some genes related to fatty acid synthesis and antioxidant enzymes in Aurantiochytrium. This research provides a low-cost and effective culture method for the commercial production of DHA by Aurantiochytrium sp. Full article

Brain lipid homeostasis is an absolute requirement for proper functionality of nerve cells and neurological performance. Current evidence demonstrates that lipid alterations are linked to neurodegenerative diseases, especially Alzheimer’s disease (AD). The complexity of the brain lipidome and its metabolic regulation has hampered the identification of critical processes associated with the onset and progression of AD. While most experimental studies have focused on the effects of known factors on the development of pathological hallmarks in AD, e.g., amyloid deposition, tau protein and neurofibrillary tangles, neuroinflammation, etc., studies addressing the causative effects of lipid alterations remain largely unexplored. In the present study, we have used a multifactor approach combining diets containing different amounts of polyunsaturated fatty acids (PUFAs), estrogen availabilities, and genetic backgrounds, i.e., wild type (WT) and APP/PS1 (FAD), to analyze the lipid phenotype of the frontal cortex in middle-aged female mice. First, we observed that severe n-3 PUFA deficiency impacts the brain n-3 long-chain PUFA (LCPUFA) composition, yet it was notably mitigated by hepatic de novo synthesis. n-6 LCPUFAs, ether-linked fatty acids, and saturates were also changed by the dietary condition, but the extent of changes was dependent on the genetic background and hormonal condition. Likewise, brain cortex phospholipids were mostly modified by the genotype (FAD>WT) with nuanced effects from dietary treatment. Cholesterol (but not sterol esters) was modified by the genotype (WT>FAD) and dietary condition (higher in DHA-free conditions, especially in WT mice). However, the effects of estrogen treatment were mostly observed in relation to phospholipid remodeling in a genotype-dependent manner. Analyses of lipid-derived variables indicate that nerve cell membrane biophysics were significantly affected by the three factors, with lower membrane microviscosity (higher fluidity) values obtained for FAD animals. In conclusion, our multifactor analyses revealed that the genotype, diet, and estrogen status modulate the lipid phenotype of the frontal cortex, both as independent factors and through their interactions. Altogether, the outcomes point to potential strategies based on dietary and hormonal interventions aimed at stabilizing the brain cortex lipid composition in Alzheimer’s disease neuropathology. Full article

Fatty acid desaturases (Fads), as key enzymes in the biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFAs), catalyze the desaturation between defined carbons of fatty acyl chains and control the degree of unsaturation of fatty acids. In the present study, two Fads genes, designated MulFadsA and MulFadsB, were identified from the genome of the dwarf surf clam Mulinia lateralis (Mollusca, Mactridae), and their spatiotemporal expression was examined. MulFadsA and MulFadsB contained the corresponding conserved functional domains and clustered closely with their respective orthologs from other mollusks. Both genes were expressed in the developmental stages and all tested adult tissues of M. lateralis, with MulFadsA exhibiting significantly higher expression levels in adult tissues than MulFadsB. Subsequently, the effects of dietary microalgae on Fads expressions in the dwarf surf clam were investigated by feeding clams with two types of unialgal diets varying in fatty acid content, i.e., Chlorella pyrenoidosa (Cp) and Platymonas helgolandica (Ph). The results show that the expressions of MulFads were significantly upregulated among adult tissues in the Cp group compared with those in the Ph group. In addition, we observed the desaturation activity of MulFadsA via heterologous expression in yeasts, revealing Δ5 desaturation activity toward PUFA substrates. Taken together, these results provide a novel perspective on M. lateralis LC-PUFA biosynthesis, expanding our understanding of fatty acid synthesis in marine mollusks. 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

Dietary supplementation with Omega-3 fatty acids seems to promote skeletal health. Therefore, their consumption at imbalanced or excessive levels has offered less beneficial or even prejudicial effects. Fish produced in aquaculture regimes are prone to develop abnormal skeletons. Although larval cultures are usually fed with diets supplemented with Omega-3 Long Chain Polyunsaturated fatty acids (LC-PUFAs), the lack of knowledge about the optimal requirements for fatty acids or about their impact on mechanisms that regulate skeletal development has impeded the design of diets that could improve bone formation during larval stages when the majority of skeletal anomalies appear. In this study, Argyrosomus regius larvae were fed different levels of Omega-3s (2.6% and 3.6% DW on diet) compared to a commercial diet. At 28 days after hatching (DAH), their transcriptomes were analyzed to study the modulation exerted in gene expression dynamics during larval development and identify impacted genes that can contribute to skeletal formation. Mainly, both levels of supplementation modulated bone-cell proliferation, the synthesis of bone components such as the extracellular matrix, and molecules involved in the interaction and signaling between bone components or in important cellular processes. The 2.6% level impacted several genes related to cartilage development, denoting a special impact on endochondral ossification, delaying this process. However, the 3.6% level seemed to accelerate this process by enhancing skeletal development. These results offered important insights into the impact of dietary Omega-3 LC-PUFAs on genes involved in the main molecular mechanism and cellular processes involved in skeletal development. Full article

With rapid growth and high lipid contents, microalgae have become promising environmentally friendly candidates for renewable biodiesel and health supplements in our era of global warming and energy depletion. Various pathways have been explored to enhance algal lipid production, especially gene editing. Previously, we found that the functional loss of PhoD-type alkaline phosphatase (AP), a phosphorus-stress indicator in phytoplankton, could lead to increased lipid contents in the model diatom Phaeodactylum tricornutum, but how the AP mutation may change lipid composition remains unexplored. This study addresses the gap in the research and investigates the effects of PhoD-type AP mutation on the lipid composition and metabolic regulation in P. tricornutum using transcriptomic and lipidomic analyses. We observed significantly modified lipid composition and elevated production of fatty acids, lysophosphatidylcholine, lysophosphatidylethanolamine, ceramide, phosphatidylinositol bisphosphate, and monogalactosylmonoacylglycerol after PhoD_45757 mutation. Meanwhile, genes involved in fatty acid biosynthesis were upregulated in mutant cells. Moreover, the mutant exhibited increased contents of ω-3 long-chain polyunsaturated fatty acid (LC-PUFA)-bound phospholipids, indicating that PhoD_45757 mutation could improve the potential bioavailability of PUFAs. Our findings indicate that AP mutation could influence cellular lipid synthesis and probably redirect carbon toward lipid production and further demonstrate that AP mutation is a promising approach for the development of high-value microalgal strains for biomedical and other applications. Full article

Glioblastoma multiforme (GBM) is one of the most aggressive gliomas. New and more effective therapeutic approaches are being sought based on studies of the various mechanisms of GBM tumorigenesis, including the synthesis and metabolism of arachidonic acid (ARA), an omega-6 polyunsaturated fatty acid (PUFA). PubMed, GEPIA, and the transcriptomics analysis carried out by Seifert et al. were used in writing this paper. In this paper, we discuss in detail the biosynthesis of this acid in GBM tumors, with a special focus on certain enzymes: fatty acid desaturase (FADS)1, FADS2, and elongation of long-chain fatty acids family member 5 (ELOVL5). We also discuss ARA metabolism, particularly its release from cell membrane phospholipids by phospholipase A₂ (cPLA₂, iPLA₂, and sPLA₂) and its processing by cyclooxygenases (COX-1 and COX-2), lipoxygenases (5-LOX, 12-LOX, 15-LOX-1, and 15-LOX-2), and cytochrome P450. Next, we discuss the significance of lipid mediators synthesized from ARA in GBM cancer processes, including prostaglandins (PGE₂, PGD₂, and 15-deoxy-Δ^12,14-PGJ₂ (15d-PGJ₂)), thromboxane A₂ (TxA₂), oxo-eicosatetraenoic acids, leukotrienes (LTB₄, LTC₄, LTD₄, and LTE₄), lipoxins, and many others. These lipid mediators can increase the proliferation of GBM cancer cells, cause angiogenesis, inhibit the anti-tumor response of the immune system, and be responsible for resistance to treatment. Full article

Recently Camelina sativa, has been genetically modified to produce oils rich in omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFA), EPA (eicosapentaenoic acid) and EPA + DHA (docosahexaenoic acid). The aim of this study was to test the feasibility of using these novel sources of de novo EPA and EPA + DHA as substitutes for marine oil in feeds for juvenile Atlantic Bluefin tuna (ABT). The results showed the oils were practical sources of n-3 LC-PUFA which could potentially replace fish oil (FO) in feeds for ABT juveniles. Fish fed the test diets (ECO, EPA alone and DCO, EPA + DHA) displayed good growth performance, survival and feed utilisation approaching that of ABT fed the reference diet (MGK) containing marine fish oil with the rank order being MGK > DCO > ECO. The test diets showed positive effects, upregulating the expression of genes of major nuclear receptors and those of lipid metabolism including digestion, LC-PUFA synthesis and antioxidant pathways. The results indicated that the DCO feed containing both DHA and EPA performed better than the ECO feed with much lower DHA. However, feeds formulated with both these oils may still require supplementary DHA to satisfy the high requirement of ABT for this essential nutrient. Full article

Phaeodactylum tricornutum is a marine diatom rich in omega-3 fatty acids, a nutraceutical-relevant product. Long chain-polyunsaturated fatty acids (LC-PUFAs) are crucial dietary components for human development and growth. With the availability of genome information and genetic engineering tools, the productivities of OMEGAs have improved, but the functional and organizational relationship of such protein-encoding genes associated with LC-PUFAs biosynthesis is still not clear. Henceforth, our study highlights the conservation pattern, functionality and interaction of LC-PUFAs protein-encoding genes via in silico analysis. The transcriptome and quantitative PCR analysis demonstrates downregulation of ACS4, ELO6b, PTD5a, and MYB106 genes associated with LC-PUFAs synthesis and upregulation of ECoAH and ACAT1 genes associated with β-oxidation in nitrogen-depleted conditions in P. tricornutum. Phylogenomics studies of LC-PUFAs protein-encoding genes show a highly conserved evolutionary pattern in various microalgal lineages. Further, for elucidating the interaction of LC-PUFA metabolic genes, subcellular networks were predicted and pathway enrichment analysis was performed, providing new insights on the crosstalk between LC-PUFA protein-encoding genes (ELO6, PTD5, ACS, and ACL1), regulatory elements (LEC2, MYB, WIN) and transporters (ABCD1). In conclusion, such extensive functional enrichment analysis will undoubtedly aid in the development of genetically engineered algal strains with enhanced production of biomolecules i.e., LC-PUFAs. Full article

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in the liver. Various mechanisms such as an increased uptake in fatty acids or de novo synthesis contribute to the development of steatosis and progression to more severe stages. Furthermore, it has been shown that impaired lipophagy, the degradation of lipids by autophagic processes, contributes to NAFLD. Through an unbiased lipidome analysis of mouse livers in a genetic model of impaired lipophagy, we aimed to determine the resulting alterations in the lipidome. Observed changes overlap with those of the human disease. Overall, the entire lipid content and in particular the triacylglycerol concentration increased under conditions of impaired lipophagy. In addition, we detected a reduction in long-chain polyunsaturated fatty acids (PUFAs) and an increased ratio of n-6 PUFAs to n-3 PUFAs, which was due to the depletion of n-3 PUFAs. Although the abundance of major phospholipid classes was reduced, the ratio of phosphatidylcholines to phosphatidylethanolamines was not affected. In conclusion, this study demonstrates that impaired lipophagy contributes to the pathology of NAFLD and is associated with an altered lipid profile. However, the lipid pattern does not appear to be specific for lipophagic alterations, as it resembles mainly that described in relation to fatty liver disease. Full article