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1.
Sci Rep ; 14(1): 12376, 2024 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811794

RESUMO

Arachidonic acid (C20: 4n-6, AA) plays a fundamental role in fish physiology, influencing growth, survival and stress resistance. However, imbalances in dietary AA can have detrimental effects on fish health and performance. Optimal AA requirements for rainbow trout have not been established. This study aimed to elucidate the effects of varying dietary AA levels on survival, growth, long-chain polyunsaturated fatty acid (LC-PUFA) biosynthetic capacity, oxylipin profiles, lipid peroxidation, and stress resistance of rainbow trout fry. Over a period of eight weeks, 4000 female rainbow trout fry at the resorptive stage (0.12 g) from their first feeding were fed diets with varying levels of AA (0.6%, 1.1% or 2.5% of total fatty acids) while survival and growth metrics were closely monitored. The dietary trial was followed by an acute confinement stress test. Notably, while the fatty acid profiles of the fish reflected dietary intake, those fed an AA-0.6% diet showed increased expression of elongase5, highlighting their inherent ability to produce LC-PUFAs from C18 PUFAs and suggesting potential AA or docosapentaenoic acidn-6 (DPAn-6) biosynthesis. However, even with this biosynthetic capacity, the trout fed reduced dietary AA had higher mortality rates. The diet had no effect on final weight (3.38 g on average for the three diets). Conversely, increased dietary AA enhanced eicosanoid production from AA, suggesting potential inflammatory and oxidative consequences. This was further evidenced by an increase in non-enzymatic lipid oxidation metabolites, particularly in the AA-2.5% diet group, which had higher levels of phytoprostanes and isoprostanes, markers of cellular oxidative damage. Importantly, the AA-1.1% diet proved to be particularly beneficial for stress resilience. This was evidenced by higher post-stress turnover rates of serotonin and dopamine, neurotransmitters central to the fish's stress response. In conclusion, a dietary AA intake of 1.1% of total fatty acids appears to promote overall resilience in rainbow trout fry.


Assuntos
Ácido Araquidônico , Ácidos Graxos Insaturados , Oncorhynchus mykiss , Oxilipinas , Estresse Fisiológico , Animais , Oncorhynchus mykiss/metabolismo , Oxilipinas/metabolismo , Ácido Araquidônico/metabolismo , Ácidos Graxos Insaturados/metabolismo , Feminino , Ração Animal/análise , Dieta/veterinária , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos
2.
BMC Musculoskelet Disord ; 25(1): 375, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734632

RESUMO

BACKGROUND: Synovitis, characterized by inflammation of the synovial membrane, is commonly induced by meniscus tears. However, significant differences in inflammatory responses and the key inflammatory mediators of synovium induced by different types of meniscal tears remain unclear. METHODS: Magnetic resonance imaging (MRI) was employed to identify the type of meniscus tear, and the quantification of synovial inflammation was assessed through H&E staining assay. Transcription and expression levels of IL-1ß and IL-6 were evaluated using bioinformatics, ELISA, RT-qPCR, and IHC of CD68 staining assays. The therapeutic potential of Docosapentaenoic Acid (DPA) was determined through network pharmacology, ELISA, and RT-qPCR assays. The safety of DPA was assessed using colony formation and EdU staining assays. RESULTS: The results indicate that both IL-1ß and IL-6 play pivotal roles in synovitis pathogenesis, with distinct expression levels across various subtypes. Among tested meniscus tears, oblique tear and bucket handle tear induced the most severe inflammation, followed by radial tear and longitudinal tear, while horizontal tear resulted in the least inflammation. Furthermore, in synovial inflammation induced by specific meniscus tears, the anterior medial tissues exhibited significantly higher local inflammation than the anterior lateral and suprapatellar regions, highlighting the clinical relevance and practical guidance of anterior medial tissues' inflammatory levels. Additionally, we identified the essential omega-3 fatty acid DPA as a potential therapeutic agent for synovitis, demonstrating efficacy in blocking the transcription and expression of IL-1ß and IL-6 with minimal side effects. CONCLUSION: These findings provide valuable insights into the nuanced nature of synovial inflammation induced by various meniscal tear classifications and contribute to the development of new adjunctive therapeutic agents in the management of synovitis.


Assuntos
Ácidos Graxos Insaturados , Interleucina-1beta , Imageamento por Ressonância Magnética , Membrana Sinovial , Sinovite , Lesões do Menisco Tibial , Lesões do Menisco Tibial/tratamento farmacológico , Lesões do Menisco Tibial/metabolismo , Sinovite/tratamento farmacológico , Sinovite/metabolismo , Sinovite/patologia , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia , Humanos , Ácidos Graxos Insaturados/farmacologia , Ácidos Graxos Insaturados/metabolismo , Ácidos Graxos Insaturados/uso terapêutico , Masculino , Interleucina-1beta/metabolismo , Animais , Interleucina-6/metabolismo , Feminino , Meniscos Tibiais/efeitos dos fármacos , Meniscos Tibiais/metabolismo , Camundongos , Modelos Animais de Doenças
3.
Int J Mol Sci ; 25(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38732139

RESUMO

The plant-derived α-linolenic acid (ALA) is an essential n-3 acid highly susceptible to oxidation, present in oils of flaxseeds, walnuts, canola, perilla, soy, and chia. After ingestion, it can be incorporated in to body lipid pools (particularly triglycerides and phospholipid membranes), and then endogenously metabolized through desaturation, elongation, and peroxisome oxidation to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), with a very limited efficiency (particularly for DHA), beta-oxidized as an energy source, or directly metabolized to C18-oxilipins. At this moment, data in the literature about the effects of ALA supplementation on metabolic syndrome (MetS) in humans are inconsistent, indicating no effects or some positive effects on all MetS components (abdominal obesity, dyslipidemia, impaired insulin sensitivity and glucoregulation, blood pressure, and liver steatosis). The major effects of ALA on MetS seem to be through its conversion to more potent EPA and DHA, the impact on the n-3/n-6 ratio, and the consecutive effects on the formation of oxylipins and endocannabinoids, inflammation, insulin sensitivity, and insulin secretion, as well as adipocyte and hepatocytes function. It is important to distinguish the direct effects of ALA from the effects of EPA and DHA metabolites. This review summarizes the most recent findings on this topic and discusses the possible mechanisms.


Assuntos
Síndrome Metabólica , Ácido alfa-Linolênico , Síndrome Metabólica/metabolismo , Humanos , Ácido alfa-Linolênico/metabolismo , Ácido alfa-Linolênico/administração & dosagem , Animais , Ácidos Graxos Insaturados/metabolismo , Suplementos Nutricionais , Resistência à Insulina
4.
BMC Genomics ; 25(1): 510, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783193

RESUMO

Domesticated safflower (Carthamus tinctorius L.) is a widely cultivated edible oil crop. However, despite its economic importance, the genetic basis underlying key traits such as oil content, resistance to biotic and abiotic stresses, and flowering time remains poorly understood. Here, we present the genome assembly for C. tinctorius variety Jihong01, which was obtained by integrating Oxford Nanopore Technologies (ONT) and BGI-SEQ500 sequencing results. The assembled genome was 1,061.1 Mb, and consisted of 32,379 protein-coding genes, 97.71% of which were functionally annotated. Safflower had a recent whole genome duplication (WGD) event in evolution history and diverged from sunflower approximately 37.3 million years ago. Through comparative genomic analysis at five seed development stages, we unveiled the pivotal roles of fatty acid desaturase 2 (FAD2) and fatty acid desaturase 6 (FAD6) in linoleic acid (LA) biosynthesis. Similarly, the differential gene expression analysis further reinforced the significance of these genes in regulating LA accumulation. Moreover, our investigation of seed fatty acid composition at different seed developmental stages unveiled the crucial roles of FAD2 and FAD6 in LA biosynthesis. These findings offer important insights into enhancing breeding programs for the improvement of quality traits and provide reference resource for further research on the natural properties of safflower.


Assuntos
Carthamus tinctorius , Ácidos Graxos Dessaturases , Ácidos Graxos Insaturados , Genoma de Planta , Carthamus tinctorius/genética , Carthamus tinctorius/metabolismo , Ácidos Graxos Insaturados/biossíntese , Ácidos Graxos Insaturados/metabolismo , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Dessaturases/metabolismo , Sementes/genética , Sementes/metabolismo , Sementes/crescimento & desenvolvimento , Genômica/métodos , Regulação da Expressão Gênica de Plantas , Anotação de Sequência Molecular
5.
Int J Biol Macromol ; 268(Pt 2): 131836, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38692553

RESUMO

Multiple species of Bifidobacterium exhibit the ability to bioconvert conjugated fatty acids (CFAs), which is considered an important pathway for these strains to promote host health. However, there has been limited progress in understanding the enzymatic mechanism of CFA bioconversion by bifidobacteria, despite the increasing number of studies identifying CFA-producing strains. The protein responsible for polyunsaturated fatty acid (PUFA) isomerization in B. breve CCFM683 has recently been discovered and named BBI, providing a starting point for exploring Bifidobacterium isomerases (BIs). This study presents the sequence classification of membrane-bound isomerases from four common Bifidobacterium species that produce CFA. Heterologous expression, purification, and enzymatic studies of the typical sequences revealed that all possess a single c9, t11 isomer as the product and share common features in terms of enzymatic properties and catalytic kinetics. Using molecular docking and alanine scanning, Lys84, Tyr198, Asn202, and Leu245 located in the binding pocket were identified as critical to the catalytic activity, a finding further confirmed by site-directed mutagenesis-based screening assays. Overall, these findings provide insightful knowledge concerning the molecular mechanisms of BIs. This will open up additional opportunities for the use of bifidobacteria and CFAs in probiotic foods and precision nutrition.


Assuntos
Bifidobacterium , Ácidos Graxos Insaturados , Bifidobacterium/enzimologia , Bifidobacterium/genética , Bifidobacterium/metabolismo , Ácidos Graxos Insaturados/metabolismo , Ácidos Graxos Insaturados/química , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Simulação de Acoplamento Molecular , Isomerismo , Cinética , Sequência de Aminoácidos , Mutagênese Sítio-Dirigida , Probióticos/metabolismo
6.
J Pharm Biomed Anal ; 245: 116196, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38723559

RESUMO

Osteoarthritis (OA) is a degenerative joint disease primarily affecting the cartilage. The therapeutic potential of the Dipsacus asper-Achyranthes bidentate herb pair for OA has been acknowledged, yet its precise mechanism remains elusive. In this study, we conducted a comprehensive analysis of metabolomic changes and therapeutic outcomes in osteoarthritic rats, employing a gas chromatography-mass spectrometry-based metabolomics approach in conjunction with histopathological and biochemical assessments. The rats were divided into six groups: control, model, positive control, Dipsacus asper treated, Achyranthes bidentata treated, and herb pair treated groups. Compared to the model group, significant reductions in levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and iNOS were observed in the treated groups. Multivariate statistical analyses were employed to investigate metabolite profile changes in serum samples and identify potential biomarkers, revealing 45 differential biomarkers, with eighteen validated using standard substances. These analytes exhibited excellent linearity across a wide concentration range (R2>0.9990), with intra- and inter-day precision RSD values below 4.69% and 4.83%, respectively. Recoveries of the eighteen analytes ranged from 93.97% to 106.59%, with RSD values under 5.72%, underscoring the method's reliability. Treatment with the herbal pair effectively restored levels of unsaturated fatty acids such as linoleic acid and arachidonic acid, along with glucogenic amino acids. Additionally, levels of phosphoric acid and citric acid were reversed, indicating restoration of energy metabolism. Collectively, these findings highlight the utility of metabolomic analysis in evaluating therapeutic efficacy and elucidating the underlying molecular mechanisms of herb pairs in OA treatment.


Assuntos
Achyranthes , Biomarcadores , Metabolismo Energético , Ácidos Graxos Insaturados , Cromatografia Gasosa-Espectrometria de Massas , Metabolômica , Osteoartrite , Ratos Sprague-Dawley , Animais , Metabolômica/métodos , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Achyranthes/química , Ratos , Metabolismo Energético/efeitos dos fármacos , Masculino , Cromatografia Gasosa-Espectrometria de Massas/métodos , Ácidos Graxos Insaturados/metabolismo , Ácidos Graxos Insaturados/sangue , Biomarcadores/sangue , Dipsacaceae/química , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
7.
Int J Mol Sci ; 25(10)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38791399

RESUMO

Oxylipins, the metabolites of polyunsaturated fatty acids, are vital in regulating cell proliferation and inflammation. Among these oxylipins, specialized pro-resolving mediators notably contribute to inflammation resolution. Previously, we showed that the specialized pro-resolving mediators isomer 11,17dihydroxy docosapentaenoic acid (11,17diHDoPE) can be synthesized in bacterial cells and exhibits anti-inflammatory effects in mammalian cells. This study investigates the in vivo impact of 11,17diHDoPE in mice exposed to particulate matter 10 (PM10). Our results indicate that 11,17diHDoPE significantly mitigates PM10-induced lung inflammation in mice, as evidenced by reduced pro-inflammatory cytokines and pulmonary inflammation-related gene expression. Metabolomic analysis reveals that 11,17diHDoPE modulates inflammation-related metabolites such as threonine, 2-keto gluconic acid, butanoic acid, and methyl oleate in lung tissues. In addition, 11,17diHDoPE upregulates the LA-derived oxylipin pathway and downregulates arachidonic acid- and docosahexaenoic acid-derived oxylipin pathways in serum. Correlation analyses between gene expression and metabolite changes suggest that 11,17diHDoPE alleviates inflammation by interfering with macrophage differentiation. These findings underscore the in vivo role of 11,17diHDoPE in reducing pulmonary inflammation, highlighting its potential as a therapeutic agent for respiratory diseases.


Assuntos
Anti-Inflamatórios , Ácidos Graxos Insaturados , Metaboloma , Material Particulado , Pneumonia , Animais , Camundongos , Metaboloma/efeitos dos fármacos , Pneumonia/metabolismo , Pneumonia/induzido quimicamente , Pneumonia/tratamento farmacológico , Material Particulado/toxicidade , Anti-Inflamatórios/farmacologia , Ácidos Graxos Insaturados/metabolismo , Masculino , Pulmão/metabolismo , Pulmão/patologia , Pulmão/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Oxilipinas/metabolismo , Metabolômica/métodos , Citocinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos
8.
World J Microbiol Biotechnol ; 40(7): 210, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38773011

RESUMO

Bioactive compounds derived from microalgae have garnered considerable attention as valuable resources for drugs, functional foods, and cosmetics. Among these compounds, photosynthetic pigments and polyunsaturated fatty acids (PUFAs) have gained increasing interest due to their numerous beneficial properties, including anti-oxidant, anti-viral, anti-bacterial, anti-fungal, anti-inflammatory, and anti-tumor effects. Several microalgae species have been identified as rich sources of bioactive compounds, including the Chlorophyceae Dunaliella and Haematococcus, the Bacillariophyta Phaeodactylum and Nitzschia, and the dinoflagellate Crypthecodinium cohnii. However, most of the reported microalgae species primarily grow through autotrophic mechanisms, resulting in low yields and high production costs of bioactive compounds. Consequently, the utilization of heterotrophic microalgae, such as Chromochloris zofingiensis and Nitzschia laevis, has shown significant advantages in the production of astaxanthin and eicosapentaenoic acid (EPA), respectively. These heterotrophic microalgae exhibit superior capabilities in synthesizing target compounds. This comprehensive review provides a thorough examination of the heterotrophic production of bioactive compounds by microalgae. It covers key aspects, including the metabolic pathways involved, the impact of cultivation conditions, and the practical applications of these compounds. The review discusses how heterotrophic cultivation strategies can be optimized to enhance bioactive compound yields, shedding light on the potential of microalgae as a valuable resource for high-value product development.


Assuntos
Processos Heterotróficos , Microalgas , Microalgas/metabolismo , Microalgas/crescimento & desenvolvimento , Ácidos Graxos Insaturados/metabolismo , Ácidos Graxos Insaturados/biossíntese , Produtos Biológicos/metabolismo , Dinoflagellida/metabolismo , Dinoflagellida/crescimento & desenvolvimento , Fotossíntese
9.
Sci Rep ; 14(1): 9888, 2024 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-38688953

RESUMO

Fatty acids have been shown to modulate glucose metabolism in vitro and in vivo. However, there is still a need for substantial evidence and mechanistic understanding in many cell types whether both saturated and unsaturated fatty acids (SFAs and UFAs) pose a similar effect and, if not, what determines the net effect of fatty acid mixes on glucose metabolism. In the present study, we asked these questions by treating granulosa cells (GCs) with the most abundant non-esterified fatty acid species in bovine follicular fluid. Results revealed that oleic and alpha-linolenic acids (UFAs) significantly increased glucose consumption compared to palmitic and stearic acids (SFAs). A significant increase in lactate production, extracellular acidification rate, and decreased mitochondrial activity indicate glucose channeling through aerobic glycolysis in UFA treated GCs. We show that insulin independent glucose transporter GLUT10 is essential for UFA driven glucose consumption, and the induction of AKT and ERK signaling pathways necessary for GLUT10 expression. To mimic the physiological conditions, we co-treated GCs with mixes of SFAs and UFAs. Interestingly, co-treatments abolished the UFA induced glucose uptake and metabolism by inhibiting AKT and ERK phosphorylation and GLUT10 expression. These data suggest that the net effect of fatty acid induced glucose uptake in GCs is determined by SFAs under physiological conditions.


Assuntos
Ácidos Graxos Insaturados , Ácidos Graxos , Proteínas Facilitadoras de Transporte de Glucose , Glucose , Glicólise , Células da Granulosa , Animais , Bovinos , Glucose/metabolismo , Glicólise/efeitos dos fármacos , Células da Granulosa/metabolismo , Células da Granulosa/efeitos dos fármacos , Feminino , Ácidos Graxos Insaturados/metabolismo , Ácidos Graxos Insaturados/farmacologia , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Ácidos Graxos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células Cultivadas
10.
BMC Plant Biol ; 24(1): 284, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627650

RESUMO

BACKGROUND: Lipids found in plant seeds are essential for controlling seed dormancy, dispersal, and defenses against biotic and abiotic stress. Additionally, these lipids provide nutrition and energy and are therefore important to the human diet as edible oils. Acer truncatum, which belongs to the Aceaceae family, is widely cultivated around the world for its ornamental value. Further because its seed oil is rich in unsaturated fatty acids (UFAs)- i.e. α-linolenic acid (ALA) and nervonic acid (NA)- and because it has been validated as a new food resource in China, the importance of A. truncatum has greatly risen. However, it remains unknown how UFAs are biosynthesized during the growth season, to what extent environmental factors impact their content, and what areas are potentially optimal for their production. RESULTS: In this study, transcriptome and metabolome of A. truncatum seeds at three representative developmental stages was used to find the accumulation patterns of all major FAs. Cumulatively, 966 metabolites and 87,343 unigenes were detected; the differential expressed unigenes and metabolites were compared between stages as follows: stage 1 vs. 2, stage 1 vs. 3, and stage 2 vs. 3 seeds, respectively. Moreover, 13 fatty acid desaturases (FADs) and 20 ß-ketoacyl-CoA synthases (KCSs) were identified, among which the expression level of FAD3 (Cluster-7222.41455) and KCS20 (Cluster-7222.40643) were consistent with the metabolic results of ALA and NA, respectively. Upon analysis of the geographical origin-affected diversity from 17 various locations, we found significant variation in phenotypes and UFA content. Notably, in this study we found that 7 bioclimatic variables showed considerable influence on FAs contents in A. truncatum seeds oil, suggesting their significance as critical environmental parameters. Ultimately, we developed a model for potentially ecological suitable regions in China. CONCLUSION: This study provides a comprehensive understanding of the relationship between metabolome and transcriptome in A. truncatum at various developmental stages of seeds and a new strategy to enhance seed FA content, especially ALA and NA. This is particularly significant in meeting the increasing demands for high-quality edible oil for human consumption. The study offers a scientific basis for A. truncatum's novel utilization as a woody vegetable oil rather than an ornamental plant, potentially expanding its cultivation worldwide.


Assuntos
Acer , Transcriptoma , Humanos , Perfilação da Expressão Gênica , Acer/genética , Acer/metabolismo , Ácidos Graxos Insaturados/metabolismo , Sementes , Metaboloma , Óleos de Plantas/metabolismo
11.
Nat Commun ; 15(1): 3431, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654015

RESUMO

The gut microbiota modulates response to hormonal treatments in prostate cancer (PCa) patients, but whether it influences PCa progression remains unknown. Here, we show a reduction in fecal microbiota alpha-diversity correlating with increase tumour burden in two distinct groups of hormonotherapy naïve PCa patients and three murine PCa models. Fecal microbiota transplantation (FMT) from patients with high PCa volume is sufficient to stimulate the growth of mouse PCa revealing the existence of a gut microbiome-cancer crosstalk. Analysis of gut microbial-related pathways in mice with aggressive PCa identifies three enzymes responsible for the metabolism of long-chain fatty acids (LCFA). Supplementation with LCFA omega-3 MAG-EPA is sufficient to reduce PCa growth in mice and cancer up-grading in pre-prostatectomy PCa patients correlating with a reduction of gut Ruminococcaceae in both and fecal butyrate levels in PCa patients. This suggests that the beneficial effect of omega-3 rich diet is mediated in part by modulating the crosstalk between gut microbes and their metabolites in men with PCa.


Assuntos
Transplante de Microbiota Fecal , Fezes , Microbioma Gastrointestinal , Neoplasias da Próstata , Masculino , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/dietoterapia , Neoplasias da Próstata/microbiologia , Animais , Humanos , Camundongos , Fezes/microbiologia , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-3/administração & dosagem , Camundongos Endogâmicos C57BL , Ácidos Graxos Insaturados/metabolismo
12.
Nat Commun ; 15(1): 3068, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594269

RESUMO

Polyunsaturated fatty acids (PUFAs), which cannot be synthesized by animals and must be supplied from the diet, have been strongly associated with human health. However, the mechanisms for their accretion remain poorly understood. Here, we show that LDL receptor-related protein 5 (LRP5), but not its homolog LRP6, selectively transports unesterified PUFAs into a number of cell types. The LDLa ligand-binding repeats of LRP5 directly bind to PUFAs and are required and sufficient for PUFA transport. In contrast to the known PUFA transporters Mfsd2a, CD36 and FATP2, LRP5 transports unesterified PUFAs via internalization to intracellular compartments including lysosomes, and n-3 PUFAs depend on this transport mechanism to inhibit mTORC1. This LRP5-mediated PUFA transport mechanism suppresses extracellular trap formation in neutrophils and protects mice from myocardial injury during ischemia-reperfusion. Thus, this study reveals a biologically important mechanism for unesterified PUFA transport to intracellular compartments.


Assuntos
Ácidos Graxos Ômega-3 , Ácidos Graxos Insaturados , Animais , Humanos , Camundongos , Dieta , Ácidos Graxos/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Insaturados/metabolismo , Receptores de LDL
13.
Microbiome ; 12(1): 73, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38605412

RESUMO

BACKGROUND: The utilization of mulberry branch fiber (MF), the largest by-product of the sericulture industry, is an important issue. Supplementation with MF as a dietary fiber for poultry may serve as a useful application. However, little is known about the effects of MF on liver lipid metabolism and egg yolk fatty acid composition of laying hens and their underlying mechanisms. In this study, we performed a multi-omics investigation to explore the variations in liver lipid metabolism, egg yolk fatty acid composition, gut microbiota, and the associations among them induced by dietary MF in laying hens. RESULTS: Dietary MF had no harmful effects on the laying performance or egg quality in laying hens. The enzyme activities associated with lipid metabolism in the liver were altered by the addition of 5% MF, resulting in reduced liver fat accumulation. Furthermore, dietary 5% MF induced the variation in the fatty acid profiles of egg yolk, and increased the polyunsaturated fatty acid (PUFA) content. We observed a significant reduction in the diversity of both gut bacteria and changes in their compositions after the addition of MF. Dietary MF significantly increased the abundance of genes involved in fatty acid biodegradation, and short-chain fatty acids biosynthesis in the gut microbiota of laying hens. The significant correlations were observed between the liver lipid metabolism enzyme activities of hepatic lipase, lipoprotein lipase, and total esterase with gut microbiota, including negative correlations with gut microbiota diversity, and multiple correlations with gut bacteria and viruses. Moreover, various correlations between the contents of PUFAs and monounsaturated fatty acids in egg yolk with the gut microbiota were obtained. Based on partial-least-squares path modeling integrated with the multi-omics datasets, we deduced the direct effects of liver enzyme activities and gut bacterial compositions on liver fat content and the roles of liver enzyme activities and gut bacterial diversity on egg yolk fatty acid composition. CONCLUSIONS: The results indicate that dietary MF is beneficial to laying hens as it reduces the liver fat and improves egg yolk fatty acid composition through the enterohepatic axis. Video Abstract.


Assuntos
Ácidos Graxos , Morus , Animais , Feminino , Ácidos Graxos/metabolismo , Gema de Ovo/metabolismo , Morus/metabolismo , Metabolismo dos Lipídeos , Galinhas/metabolismo , Dieta , Ácidos Graxos Insaturados/metabolismo , Ração Animal/análise , Suplementos Nutricionais
15.
JPEN J Parenter Enteral Nutr ; 48(4): 479-485, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38566550

RESUMO

BACKGROUND: Extracellular vesicles in human milk are critical in supporting newborn growth and development. Bioavailability of dietary extracellular vesicles may depend on the composition of membrane lipids. Single-nucleotide polymorphisms (SNPs) in the fatty acid desaturase gene cluster impact the content of long-chain polyunsaturated fatty acids in human milk phospholipids. This study investigated the relation between variation in FADS1 and FADS2 with the content of polyunsaturated fatty acids in extracellular vesicles from human milk. METHODS: Milk was obtained from a cohort of mothers (N = 70) at 2-4 weeks of lactation. SNPs in the FADS gene locus were determined using pyrosequencing for rs174546 in FADS1 and rs174575 in FADS2. Quantitative lipidomic analysis of polyunsaturated fatty acids in human milk and extracellular vesicles from human milk was completed by gas chromatography-mass spectrometry. RESULTS: The rs174546 and rs174575 genotypes were independent predictors of the arachidonic acid content in extracellular vesicles. The rs174546 genotype also predicted eicosapentaenoic acid and docosahexaenoic acid in extracellular vesicles. The reduced content of long-chain polyunsaturated fatty acids in extracellular vesicles in human milk may be due to lower fatty acid desaturase activity in mothers who are carriers of the A allele in rs174546 or the G allele in rs174575. CONCLUSION: The polyunsaturated fatty acid composition of milk extracellular vesicles is predicted by the FADS genotype. These findings yield novel insights regarding extracellular vesicle content and composition that can inform the design of future research to explore how lipid metabolites impact the bioavailability of human milk extracellular vesicles.


Assuntos
Dessaturase de Ácido Graxo Delta-5 , Vesículas Extracelulares , Ácidos Graxos Dessaturases , Ácidos Graxos Insaturados , Genótipo , Leite Humano , Polimorfismo de Nucleotídeo Único , Humanos , Leite Humano/química , Leite Humano/metabolismo , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Dessaturases/metabolismo , Feminino , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , Ácidos Graxos Insaturados/análise , Ácidos Graxos Insaturados/metabolismo , Adulto , Estudos de Associação Genética , Estudos de Coortes , Lactação/genética , Lactação/metabolismo , Ácidos Docosa-Hexaenoicos/análise , Ácidos Docosa-Hexaenoicos/metabolismo
16.
J Biol Chem ; 300(5): 107291, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38636661

RESUMO

Mutations in the adiponectin receptor 1 gene (AdipoR1) lead to retinitis pigmentosa and are associated with age-related macular degeneration. This study explores the effects of AdipoR1 gene deficiency in mice, revealing a striking decline in ω3 polyunsaturated fatty acids (PUFA), an increase in ω6 fatty acids, and elevated ceramides in the retina. The AdipoR1 deficiency impairs peroxisome proliferator-activated receptor α signaling, which is crucial for FA metabolism, particularly affecting proteins associated with FA transport and oxidation in the retina and retinal pigmented epithelium. Our lipidomic and proteomic analyses indicate changes that could affect membrane composition and viscosity through altered ω3 PUFA transport and synthesis, suggesting a potential influence of AdipoR1 on these properties. Furthermore, we noted a reduction in the Bardet-Biedl syndrome proteins, which are crucial for forming and maintaining photoreceptor outer segments that are PUFA-enriched ciliary structures. Diminution in Bardet-Biedl syndrome-proteins content combined with our electron microscopic observations raises the possibility that AdipoR1 deficiency might impair ciliary function. Treatment with inhibitors of ceramide synthesis led to substantial elevation of ω3 LC-PUFAs, alleviating photoreceptor degeneration and improving retinal function. These results serve as the proof of concept for a ceramide-targeted strategy to treat retinopathies linked to PUFA deficiency, including age-related macular degeneration.


Assuntos
Ceramidas , Receptores de Adiponectina , Retina , Animais , Receptores de Adiponectina/metabolismo , Receptores de Adiponectina/genética , Camundongos , Ceramidas/metabolismo , Retina/metabolismo , Retina/patologia , Camundongos Knockout , Ácidos Graxos Insaturados/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Degeneração Macular/metabolismo , Degeneração Macular/patologia , Degeneração Macular/genética
17.
Genes (Basel) ; 15(3)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38540424

RESUMO

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.


Assuntos
Bivalves , Chlorella , Animais , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Insaturados/genética , Ácidos Graxos Insaturados/metabolismo , Chlorella/metabolismo , Bivalves/genética , Bivalves/metabolismo , Ácidos Graxos/metabolismo
18.
Int J Mol Sci ; 25(6)2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38542213

RESUMO

The microalgae Vischeria sp. IPPAS C-70 produces eicosapentaenoic acid. Several stresses cause the formation of fatty acid peaks that resemble hexadecadienoic acids. We used the integrated technique including TLC, HPLC, and GC-MS to search and determine these fatty acids. Double bond positioning in these fatty acids indicated that they were conjugated dienes and allenes. We identified and described natural nine isomers of C16 polyunsaturated fatty acids, including common methylene-interrupted dienes (Δ6,9-16:2, Δ7,10-16:2, Δ9,12-16:2), and unusual conjugated dienes (Δ6,8-, Δ7,9-, Δ8,10-, Δ9,11-, and Δ10,12-16:2), as well as allenic diene (Δ9,10-16:2). We hypothesize that the formation of conjugated dienes and allenes among fatty acids is the result of oxidative stress caused by H2O2. Hydrogen peroxide also caused an increase in saturated at the expense of unsaturated fatty acids, suggesting inhibition either fatty acid desaturases activities or the corresponding gene expression.


Assuntos
Ácidos Graxos , Peróxido de Hidrogênio , Ácidos Graxos/metabolismo , Ácidos Graxos Insaturados/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Estresse Oxidativo , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Dessaturases/metabolismo
19.
Biotechnol Lett ; 46(3): 373-383, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38493279

RESUMO

OBJECTIVE: Currently, there is lack of a consistent and highly enriched source for docosapentaenoic acid (n-3 DPA, C22:5), and this work report the isolation of microorganism that naturally produces n-3 DPA. RESULTS: In this work, we screened microorganisms in our culture collections with the goal to isolate a strain with high levels of n-3 DPA. We isolated a strain of Sphaeroforma arctica that produces up to 11% n-3 DPA in total fatty acid and has a high n-3 DPA to DHA/EPA ratio. The cell growth of the isolated strain was characterized using microscopy imaging and flow cytometer technologies to confirm the coenocytic pattern of cell divisions previously described in S. arctica. Our novel isolate of S. arctica grew more robustly and produced significantly more n-3 DPA compared to previously isolated and described strains indicating the uniqueness of the discovered strain. CONCLUSION: Overall, this work reports a first isolate n-3 DPA producing microorganism and establishes the foundation for future strain improvement and elucidation of the physiological function of this LC-PUFA for human nutrition and health.


Assuntos
Ácidos Graxos Insaturados , Ácidos Graxos Insaturados/metabolismo , Estramenópilas/metabolismo , Estramenópilas/isolamento & purificação
20.
Biochim Biophys Acta Biomembr ; 1866(5): 184310, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38479610

RESUMO

Fumonisin B1 (FB1), a food-borne mycotoxin, is a cancer promoter in rodent liver and augments proliferation of initiated cells while inhibiting the growth of normal hepatocytes by disrupting lipid biosynthesis at various levels. HepG2 cancer cells exhibited resistance to FB1-induced toxic effects presumably due to their low content of polyunsaturated fatty acids (PUFA) even though FB1-typical lipid changes were observed, e.g. significantly increased phosphatidylethanolamine (PE), decreased sphingomyelin and cholesterol content, increased sphinganine (Sa) and sphinganine/sphingosine ratio, increased C18:1ω-9, decreased C20:4ω-6 content in PE and decreased C20:4ω-6_PC/PE ratio. Increasing PUFA content of HepG2 cells with phosphatidylcholine (PC) vesicles containing C20:4ω-6 (SAPC) or C22:6ω-3 (SDPC) disrupted cell survival, cellular redox status and induced oxidative stress and apoptosis. A partially protective effect of FB1 was evident in PUFA-enriched HepG2 cells which may be related to the FB1-induced reduction in oxidative stress and the disruption of key cell membrane constituents indicative of a resistant lipid phenotype. Interactions between different ω-6 and ω-3 PUFA, membrane constituents including cholesterol, and the glycerophospho- and sphingolipids and FB1 in this cell model provide further support for the resistant lipid phenotype and its role in the complex cellular effects underlying the cancer promoting potential of the fumonisins.


Assuntos
Apoptose , Ácidos Graxos Insaturados , Fumonisinas , Fumonisinas/farmacologia , Humanos , Células Hep G2 , Ácidos Graxos Insaturados/farmacologia , Ácidos Graxos Insaturados/metabolismo , Apoptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Colesterol/metabolismo
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