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1.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1869(8): 159541, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39097082

RESUMO

It is becoming increasingly clear that not only unicellular, photoautotrophic eukaryotes, plants, and fungi, but also invertebrates are capable of synthesizing ω3 long-chain polyunsaturated fatty acids (LC-PUFA) de novo. However, the distribution of this anabolic capacity among different invertebrate groups and its implementation at the gene and protein level are often still unknown. This study investigated the PUFA pathways in common soil fauna, i.e. two nematode and two Collembola species. Of these, one species each (Panagrellus redivivus, Folsomia candida) was assumed to produce ω3 LC-PUFA de novo, while the others (Acrobeloides bodenheimeri, Isotoma caerulea) were supposed to be unable to do so. A highly labeled oleic acid (99 % 13C) was supplemented and the isotopic signal was used to trace its metabolic path. All species followed the main pathway of lipid biosynthesis. However, in A. bodenheimeri this terminated at arachidonic acid (ω6 PUFA), whereas the other three species continued the pathway to eicosapentaenoic acid (ω3 PUFA), including I. caerulea. For the nematode P. redivivus the identification and functional characterization of four new fatty acid desaturase (FAD) genes was performed. These genes encode the FAD activities Δ9, Δ6, and Δ5, respectively. Additionally, the Δ12 desaturase was analyzed, yet the observed activity of an ω3 FAD could not be attributed to a coding gene. In the Collembola F. candida, 11 potential first desaturases (Δ9) and 13 front-end desaturases (Δ6 or Δ5 FADs) have been found. Further sequence analysis indicates the presence of omega FADs, specifically Δ12, which are likely derived from Δ9 FADs.


Assuntos
Artrópodes , Ácidos Graxos Insaturados , Nematoides , Solo , Animais , Nematoides/metabolismo , Nematoides/genética , Ácidos Graxos Insaturados/metabolismo , Ácidos Graxos Insaturados/biossíntese , Artrópodes/metabolismo , Artrópodes/genética , Solo/química , Solo/parasitologia , Ácidos Graxos Dessaturases/metabolismo , Ácidos Graxos Dessaturases/genética
2.
Ann Bot ; 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39082745

RESUMO

BACKGROUND: Chia (Salvia hispanica L.) seeds have become increasingly popular among health-conscious consumers due to their high content of ω-3 fatty acids, which provide various health benefits. Comprehensive chemical analyses of chia seeds' fatty acids and proteins have been conducted, revealing their functional properties. Recent studies have confirmed the high ω-3 content of chia seed oil and have hinted at additional functional characteristics. SCOPE: This review article aims to provide an overview of the botanical, morphological, and biochemical features of chia plants, seeds, and seed mucilage. Additionally, we discuss the recent developments in genetic and molecular research on chia, including the latest transcriptomic and functional studies that examine the genes responsible for chia fatty acid biosynthesis. In recent years, research on chia seeds has shifted its focus from studying the physicochemical characteristics and chemical composition of seeds to understanding the metabolic pathways and molecular mechanisms that contribute to their nutritional benefits. This has led to a growing interest in various pharmaceutical, nutraceutical, and agricultural applications of chia. In this context, we discuss the latest research on chia, as well as the questions that remain unanswered, and identify areas that require further exploration. CONCLUSIONS: Nutraceutical compounds associated with significant health benefits including ω-3 PUFAs, proteins, and phenolic compounds with antioxidant activity have been measured in high quantities in chia seeds. However, comprehensive investigations through both in vitro experiments and in vivo animal and controlled human trials are expected to provide greater clarity on the medicinal, antimicrobial, and antifungal effects of chia seeds. The recently published genome of chia and gene editing technologies, such as CRISPR, facilitate functional studies deciphering molecular mechanisms of biosynthesis and metabolic pathways in this crop. This necessitates development of stable transformation protocols and creation of a publicly available lipid database, mutant collection, and large-scale transcriptomic datasets for chia.

3.
Rev Cardiovasc Med ; 25(4): 142, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-39076540

RESUMO

Multiple factors cause atherosclerosis, meaning its pathogenesis is complex, and has not been fully elucidated. Polyunsaturated fatty acids are a member of the fatty acid family, which are critical nutrients for mammalian growth and development. The types of polyunsaturated fatty acids ingested, their serum levels, and fatty acid desaturase can influence the atherosclerotic disease progression. The fatty acid desaturase gene cluster can regulate fatty acid desaturase activity and further affect atherosclerosis. This study reviewed the research progress on the effects of polyunsaturated fatty acids on atherosclerosis regulated by fatty acid desaturase and the relationship between genetic variants of the fatty acid desaturase gene cluster and atherosclerotic cardiovascular disease.

4.
J Fungi (Basel) ; 10(7)2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39057381

RESUMO

Delta-12 fatty acid desaturases (FAD2s) actively regulate stress responses and cell differentiation in living organisms. In this study, six homologous FAD2 genes were identified based on the genome sequence of Lentinula edodes. Then, the six FAD2 protein sequences were analyzed using bioinformatics tools, including ExPASy ProtParam, SignalP, TMHMM, and TargetP. These analyses were performed to predict the physical and chemical properties, signal peptides, and transmembrane and conserved domains of these proteins. The polypeptide sequences were aligned, and a maximum likelihood phylogenetic tree was constructed using MEGA 7.0 software to elucidate the phylogenetic relationships between homologous FAD2 sequences. The results demonstrated that the FAD2 proteins contained three conserved histidine-rich regions (HXXXH, HXXHH, and HXXHH), which included eight histidine residues. The linoleic acid content and FAD2 enzyme activity were further analyzed, and the levels in the mutagenic heat-tolerant strain 18N44 were lower than those in the wild-type strain 18. Interestingly, the expression levels of the FAD2-2 and FAD2-3 genes under heat stress in strain 18N44 were lower than those in strain 18. These findings indicated that FAD2-2 and FAD2-3 may play major roles in the synthesis of linoleic acid during heat stress.

5.
Mol Nutr Food Res ; 68(15): e2400201, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38961528

RESUMO

SCOPE: Single nucleotide polymorphisms (SNP) in the fatty acid desaturase 1 (FADS1) gene is suggested as risk factor of metabolic diseases in genome-wide association studies (GWAS). This study hypothesized that FADS1_rs174546T associates with serum triglycerides (TG) in Korean Genome and Epidemiology Study (KoGES). In addition, functional study of SNP genotypes in cultured cells is performed. METHODS AND RESULTS: FADS1_rs174546T is associated with high level of serum TG (effect size of variant: 6.48 ± 1.84 mg dL-1) in Korean individuals (normotriglyceridemia, n = 5128; hypertriglyceridemia, n = 3714). Functional study in cells with FADS1_rs174546T, shows reduced transcriptional activity, when compared with rs174546C. MiR-6728-3p, which is predicted to bind with rs174546T, decreases transcriptional activity of rs174546T but not in rs174546C, and it is reversed by miR-6728-3p inhibitor. Formononetin is selected as binding molecule to 3'-UTR of FADS1 and increases luciferase activity in both rs174546 (C/T). Moreover, formononetin compensates for the reduced luciferase activity by rs174546T and miR-6728-3p. Formononetin also increases endogenous FADS1 expression and long-chain polyunsaturated fatty acid (LC-PUFA) ratio. CONCLUSION: FADS1_rs174546T is a crucial risk factor for hypertriglyceridemia in the Koreans potentially through the interaction with miR-6728-3p. Formononetin can be a potent dietary intervention to prevent and improve hypertriglyceridemia in both rs174546 (C/T) populations.


Assuntos
Dessaturase de Ácido Graxo Delta-5 , Ácidos Graxos Dessaturases , Polimorfismo de Nucleotídeo Único , Triglicerídeos , Ácidos Graxos Dessaturases/genética , Humanos , República da Coreia , Masculino , Triglicerídeos/sangue , Feminino , Pessoa de Meia-Idade , MicroRNAs/genética , Hipertrigliceridemia/genética , Hipertrigliceridemia/sangue , Povo Asiático/genética , Adulto
6.
Plants (Basel) ; 13(11)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38891253

RESUMO

Camellia oil is valuable as an edible oil and serves as a base material for a range of high-value products. Camellia plants of significant economic importance, such as Camellia sinensis and Camellia oleifera, have been classified into sect. Thea and sect. Oleifera, respectively. Fatty acid desaturases play a crucial role in catalyzing the formation of double bonds at specific positions of fatty acid chains, leading to the production of unsaturated fatty acids and contributing to lipid synthesis. Comparative genomics results have revealed that expanded gene families in oil tea are enriched in functions related to lipid, fatty acid, and seed processes. To explore the function of the FAD gene family, a total of 82 FAD genes were identified in tea and oil tea. Transcriptome data showed the differential expression of the FAD gene family in mature seeds of tea tree and oil tea tree. Furthermore, the structural analysis and clustering of FAD proteins provided insights for the further exploration of the function of the FAD gene family and its role in lipid synthesis. Overall, these findings shed light on the role of the FAD gene family in Camellia plants and their involvement in lipid metabolism, as well as provide a reference for understanding their function in oil synthesis.

7.
Plants (Basel) ; 13(11)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38891317

RESUMO

The omega-3 fatty acid desaturase enzyme gene FAD3 is responsible for converting linoleic acid to linolenic acid in plant fatty acid synthesis. Despite limited knowledge of its role in cotton growth, our study focused on GhFAD3-4, a gene within the FAD3 family, which was found to promote fiber elongation and cell wall thickness in cotton. GhFAD3-4 was predominantly expressed in elongating fibers, and its suppression led to shorter fibers with reduced cell wall thickness and phosphoinositide (PI) and inositol triphosphate (IP3) levels. Transcriptome analysis of GhFAD3-4 knock-out mutants revealed significant impacts on genes involved in the phosphoinositol signaling pathway. Experimental evidence demonstrated that GhFAD3-4 positively regulated the expression of the GhBoGH3B and GhPIS genes, influencing cotton fiber development through the inositol signaling pathway. The application of PI and IP6 externally increased fiber length in GhFAD3-4 knock-out plants, while inhibiting PI led to a reduced fiber length in GhFAD3-4 overexpressing plants. These findings suggest that GhFAD3-4 plays a crucial role in enhancing fiber development by promoting PI and IP3 biosynthesis, offering the potential for breeding cotton varieties with superior fiber quality.

8.
Sci Rep ; 14(1): 13116, 2024 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849435

RESUMO

Stearoyl-CoA desaturase 1 (SCD1) is an attractive target for cancer therapy. However, the clinical efficacy of SCD1 inhibitor monotherapy is limited. There is thus a need to elucidate the mechanisms of resistance to SCD1 inhibition and develop new therapeutic strategies for combination therapy. In this study, we investigated the molecular mechanisms by which cancer cells acquire resistance to endoplasmic reticulum (ER) stress-dependent cancer cell death induced by SCD1 inhibition. SCD1 inhibitor-sensitive and -resistant cancer cells were treated with SCD1 inhibitors in vitro, and SCD1 inhibitor-sensitive cancer cells accumulated palmitic acid and underwent ER stress response-induced cell death. Conversely, SCD1-resistant cancer cells did not undergo ER stress response-induced cell death because fatty acid desaturase 2 (FADS2) eliminated the accumulation of palmitic acid. Furthermore, genetic depletion using siRNA showed that FADS2 is a key determinant of sensitivity/resistance of cancer cells to SCD1 inhibitor. A549 cells, an SCD1 inhibitor-resistant cancer cell line, underwent ER stress-dependent cancer cell death upon dual inhibition of SCD1 and FADS2. Thus, combination therapy with SCD1 inhibition and FADS2 inhibition is potentially a new cancer therapeutic strategy targeting fatty acid metabolism.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Estresse do Retículo Endoplasmático , Ácidos Graxos Dessaturases , Estearoil-CoA Dessaturase , Estearoil-CoA Dessaturase/metabolismo , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/antagonistas & inibidores , Humanos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Dessaturases/metabolismo , Linhagem Celular Tumoral , Células A549 , Ácido Palmítico/farmacologia , Morte Celular/efeitos dos fármacos , Neoplasias/metabolismo , Neoplasias/genética , Neoplasias/patologia , Neoplasias/tratamento farmacológico
9.
J Agric Food Chem ; 72(25): 14177-14190, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38875711

RESUMO

Understanding the evolutionary genetics of food intake regulation in domesticated animals has relevance to evolutionary biology, animal improvement, and obesity treatment. Here, we observed that the fatty acid desaturase gene (Bmdesat5), which regulates food intake, is suppressed in domesticated silkworms, but expressed in the salivary glands of the wild silkworm Bombyx mandarina. The content of its catalytic product, cis-vaccenic acid, was related to the expression levels of Bmdesat5 in the salivary glands of domesticated and wild silkworm strains. These two strains also showed significant differences in food intake. Using orally administering cis-vaccenic acid and transgenic-mediated overexpression, we verified that cis-vaccenic acid functions as a satiation signal, regulating food intake and growth in silkworms. Selection analysis showed that Bmdesat5 experienced selection, especially in the potential promoter, 5'-untranslated, and intron regions. This study highlights the importance of the decrement of satiety in silkworm domestication and provides new insights into the potential involvement of salivary glands in the regulation of satiety in animals, by acting as a supplement to gut-brain nutrient signaling.


Assuntos
Bombyx , Ingestão de Alimentos , Ácidos Graxos Dessaturases , Proteínas de Insetos , Glândulas Salivares , Animais , Bombyx/genética , Bombyx/enzimologia , Bombyx/metabolismo , Glândulas Salivares/metabolismo , Glândulas Salivares/enzimologia , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Ingestão de Alimentos/genética , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Dessaturases/metabolismo , Domesticação
10.
Am J Clin Nutr ; 120(2): 360-368, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38879016

RESUMO

BACKGROUND: A fatty acid desaturase (FADS) insertion-deletion (Indel) polymorphism (rs66698963) influences the expression of FADS1, which controls the synthesis of n-6 highly unsaturated fatty acid (HUFA) arachidonic acid (AA). The anti-inflammatory activity of the n-3 HUFA eicosapentaenoic acid (EPA) may be explained by competition with AA for proinflammatory lipid mediator synthesis. A precision medicine approach based on stratification by FADS Indel genotype could identify individuals, who benefit from greatest disease risk reduction by n-3 HUFAs. OBJECTIVES: We tested the hypothesis that the FADS insertion (I) allele predicts colorectal polyp risk reduction in a secondary analysis of the randomized, placebo-controlled, 2×2 factorial seAFOod polyp prevention trial of EPA 2000 mg daily and aspirin 300 mg daily for 12 mo (ISRCTN05926847). METHODS: Participant Indel genotype was determined by polymerase chain reaction (PCR) blind to trial outcomes. Colorectal polyp outcomes were included in negative binomial (polyp number) and logistic (polyp detection rate [PDR; percentage with one or more polyps]) regression models comparing each active intervention with its placebo. Presence of ≥1 Indel I allele and an interaction term (I allele × active intervention) were covariates. RESULTS: In 528 participants with colonoscopy and FADS Indel data, EPA use irrespective of Indel genotype, was not associated with reduced colorectal polyp number (incidence rate ratio [IRR]: 0.92; 95% confidence interval: 0.74, 1.16), mirroring original seAFOod trial analysis. However, the presence of ≥1 I allele identified EPA users with a significant reduction in colorectal polyp number (IRR: 0.50 [0.28, 0.90]), unlike aspirin, for which there was no interaction. Similar findings were obtained for the PDR. CONCLUSIONS: The FADS Indel I allele identified individuals, who displayed colorectal polyp prevention by EPA with a similar effect size to aspirin. Assessment of rs66698963 as a biomarker of therapeutic response to n-3 HUFAs in other populations and healthcare settings is warranted. The seAFOod polyp prevention trial and STOP-ADENOMA study were registered at International Standard Randomised Controlled Trial Number registry as ISRCTN05926847.


Assuntos
Dessaturase de Ácido Graxo Delta-5 , Ácido Eicosapentaenoico , Ácidos Graxos Dessaturases , Alimentos Marinhos , Humanos , Feminino , Ácido Eicosapentaenoico/administração & dosagem , Masculino , Ácidos Graxos Dessaturases/genética , Pessoa de Meia-Idade , Idoso , Pólipos do Colo/genética , Mutação INDEL , Polimorfismo Genético , Neoplasias Colorretais/prevenção & controle , Neoplasias Colorretais/genética , Aspirina/administração & dosagem , Aspirina/uso terapêutico , Genótipo
11.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1869(6): 159498, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38703945

RESUMO

The biosynthetic capability of the long-chain polyunsaturated fatty acids (LC-PUFA) in teleosts are highly diversified due to evolutionary events such as gene loss and subsequent neo- and/or sub-functionalisation of enzymes encoded by existing genes. In the present study, we have comprehensively characterised genes potentially involved in LC-PUFA biosynthesis, namely one front-end desaturase (fads2) and eight fatty acid elongases (elovl1a, elovl1b, elovl4a, elovl4b, elovl5, elovl7, elovl8a and elovl8b) from an amphidromous teleost, Ayu sweetfish, Plecoglossus altivelis. Functional analysis confirmed Fads2 with Δ6, Δ5 and Δ8 desaturase activities towards multiple PUFA substrates and several Elovl enzymes exhibited elongation capacities towards C18-20 or C18-22 PUFA substrates. Consequently, P. altivelis possesses a complete enzymatic capability to synthesise physiologically important LC-PUFA including arachidonic acid (ARA, 20:4n-6), eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) from their C18 precursors. Interestingly, the loss of elovl2 gene in P. altivelis was corroborated by genomic and phylogenetic analyses. However, this constraint would possibly be overcome by the function of alternative Elovl enzymes, such as Elovl1b, which has not hitherto been functionally characterised in teleosts. The present study contributes novel insights into LC-PUFA biosynthesis in the relatively understudied teleost group, Osmeriformes (Stomiati), thereby enhancing our understanding of the complement of LC-PUFA biosynthetic genes within teleosts.


Assuntos
Ácidos Graxos Dessaturases , Elongases de Ácidos Graxos , Ácidos Graxos Insaturados , Osmeriformes , Animais , Ácidos Graxos Insaturados/metabolismo , Ácidos Graxos Insaturados/biossíntese , Ácidos Graxos Insaturados/genética , Osmeriformes/metabolismo , Osmeriformes/genética , Ácidos Graxos Dessaturases/metabolismo , Ácidos Graxos Dessaturases/genética , Elongases de Ácidos Graxos/metabolismo , Elongases de Ácidos Graxos/genética , Filogenia , Proteínas de Peixes/metabolismo , Proteínas de Peixes/genética , Vias Biossintéticas/genética , Acetiltransferases/metabolismo , Acetiltransferases/genética
12.
Int J Mol Sci ; 25(9)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38732052

RESUMO

Fatty acid desaturase 1 (FADS1) is a rate-limiting enzyme in long-chain polyunsaturated fatty acid (LCPUFA) synthesis. Reduced activity of FADS1 was observed in metabolic dysfunction-associated steatotic liver disease (MASLD). The aim of this study was to determine whether adeno-associated virus serotype 8 (AAV8) mediated hepatocyte-specific overexpression of Fads1 (AAV8-Fads1) attenuates western diet-induced metabolic phenotypes in a rat model. Male weanling Sprague-Dawley rats were fed with a chow diet, or low-fat high-fructose (LFHFr) or high-fat high-fructose diet (HFHFr) ad libitum for 8 weeks. Metabolic phenotypes were evaluated at the endpoint. AAV8-Fads1 injection restored hepatic FADS1 protein levels in both LFHFr and HFHFr-fed rats. While AAV8-Fads1 injection led to improved glucose tolerance and insulin signaling in LFHFr-fed rats, it significantly reduced plasma triglyceride (by ~50%) and hepatic cholesterol levels (by ~25%) in HFHFr-fed rats. Hepatic lipidomics analysis showed that FADS1 activity was rescued by AAV8-FADS1 in HFHFr-fed rats, as shown by the restored arachidonic acid (AA)/dihomo-γ-linolenic acid (DGLA) ratio, and that was associated with reduced monounsaturated fatty acid (MUFA). Our data suggest that the beneficial role of AAV8-Fads1 is likely mediated by the inhibition of fatty acid re-esterification. FADS1 is a promising therapeutic target for MASLD in a diet-dependent manner.


Assuntos
Dessaturase de Ácido Graxo Delta-5 , Dieta Ocidental , Ácidos Graxos Dessaturases , Hepatócitos , Animais , Masculino , Ratos , Dessaturase de Ácido Graxo Delta-5/metabolismo , Dependovirus/genética , Dieta Ocidental/efeitos adversos , Modelos Animais de Doenças , Ácidos Graxos Dessaturases/metabolismo , Ácidos Graxos Dessaturases/genética , Frutose/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Fenótipo , Ratos Sprague-Dawley , Triglicerídeos/metabolismo
13.
Bioinform Biol Insights ; 18: 11779322241248908, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711943

RESUMO

Fatty acid desaturase (FAD) is the key enzyme that leads to the formation of unsaturated fatty acids by introducing double bonds into hydrocarbon chains, and it plays a critical role in plant lipid metabolism. However, no data are available on enzyme-associated genes in argan trees. In addition, a candidate gene approach was adopted to identify and characterize the gene sequences of interest that are potentially involved in oil quality and abiotic stress. Based on phylogenetic analyses, 18 putative FAD genes of Argania spinosa L. (AsFAD) were identified and assigned to three subfamilies: stearoyl-ACP desaturase (SAD), Δ-12 desaturase (FAD2/FAD6), and Δ-15 desaturase (FAD3/FAD7). Furthermore, gene structure and motif analyses revealed a conserved exon-intron organization among FAD members belonging to the various oil crops studied, and they exhibited conserved motifs within each subfamily. In addition, the gene structure shows a wide variation in intron numbers, ranging from 0 to 8, with two highly conserved intron phases (0 and 1). The AsFAD and AsSAD subfamilies consist of three (H(X)2-4H, H(X)2-3HH, and H/Q (X)2-3HH) and two (EEN(K)RHG and DEKRHE) conserved histidine boxes, respectively. A set of primer pairs were designed for each FAD gene, and tested on DNA extracted from argan leaves, in which all amplicons of the expected size were produced. These findings of candidate genes in A spinosa L. will provide valuable knowledge that further enhances our understanding of the potential roles of FAD genes in the quality of oil and abiotic stress in the argan tree.

14.
Front Biosci (Landmark Ed) ; 29(4): 131, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38682200

RESUMO

BACKGROUND: The endogenous metabolism of polyunsaturated fatty acids is regulated by the fatty acid desaturase (FADS) gene cluster and is strongly associated with diseases such as atherosclerosis, dyslipidemia, and type 2 diabetes. However, the association between FADS and atherosclerosis remains a subject of debate. METHODS: In this study, we specifically investigated the physiological role of Δ-5 fatty acid desaturase (FADS1) in aortic and peripheral vessel (namely, the femoral artery) atherosclerosis by targeting the selective knockdown of hepatic Fads1 in apolipoprotein E-null (ApoE-⁣/-) mice with antisense oligonucleotides (ASOs). RESULTS: Knockdown of hepatic Fads1 in ApoE-⁣/- mice exacerbated aortic atherosclerosis and non-alcoholic fatty liver disease (NAFLD), resulting in weight loss. Upregulation of FADS1 mRNA expression in more severe atherosclerosis vascular tissues potentially caused the upregulation of angiopoietin-like 4 expression. CONCLUSIONS: Our study demonstrated that knockdown of hepatic Fads1 in ApoE-⁣/- mice aggravates spontaneous atherosclerosis and NAFLD but does not affect peripheral atherosclerosis (femoral artery) induced by vascular cuff combined with tandem stenosis.


Assuntos
Apolipoproteínas E , Aterosclerose , Dessaturase de Ácido Graxo Delta-5 , Ácidos Graxos Dessaturases , Fígado , Animais , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Dessaturases/metabolismo , Dessaturase de Ácido Graxo Delta-5/metabolismo , Aterosclerose/genética , Aterosclerose/metabolismo , Fígado/metabolismo , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Camundongos , Técnicas de Silenciamento de Genes , Masculino , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oligonucleotídeos Antissenso/genética
15.
J Fungi (Basel) ; 10(4)2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38667959

RESUMO

Polyunsaturated fatty acids (PUFAs), as important components of lipids, play indispensable roles in the development of all organisms. ∆12 fatty acid desaturase (FAD12) is a speed-determining step in the biosynthesis of PUFAs. Here, we report the characterization of FAD12 in Fusarium graminearum, which is the prevalent agent of Fusarium head blight, a destructive plant disease worldwide. The results demonstrated that deletion of the FgFAD12 gene resulted in defects in vegetative growth, conidial germination and plant pathogenesis but not sexual reproduction. A fatty acid analysis further proved that the deletion of FgFAD12 restrained the reaction of oleic acid to linoleic acid, and a large amount of oleic acid was detected in the cells. Moreover, the ∆Fgfad12 mutant showed increased resistance to osmotic stress and reduced tolerance to oxidative stress. The expression of FgFAD12 did show a temperature-dependent manner, which was not affected at a low temperature of 10 °C when compared to 25 °C. RNA-seq analysis further demonstrated that most genes enriched in fatty acid metabolism, the biosynthesis of unsaturated fatty acids, fatty acid biosynthesis, fatty acid degradation, steroid biosynthesis and fatty acid elongation pathways were significantly up-regulated in the ∆Fgfad12 mutants. Overall, our results indicate that FgFAD12 is essential for linoleic acid biosynthesis and plays an important role in the infection process of F. graminearum.

16.
Genes (Basel) ; 15(3)2024 03 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
17.
Mar Drugs ; 22(2)2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38393053

RESUMO

The marine red microalga Porphyridium can simultaneously synthesize long-chain polyunsaturated fatty acids, including eicosapentaenoic acid (C20:5, EPA) and arachidonic acid (C20:4, ARA). However, the distribution and synthesis pathways of EPA and ARA in Porphyridium are not clearly understood. In this study, Porphyridium cruentum CCALA 415 was cultured in nitrogen-replete and nitrogen-limited conditions. Fatty acid content determination, transcriptomic, and lipidomic analyses were used to investigate the synthesis of ARA and EPA. The results show that membrane lipids were the main components of lipids, while storage lipids were present in a small proportion in CCALA 415. Nitrogen limitation enhanced the synthesis of storage lipids and ω6 fatty acids while inhibiting the synthesis of membrane lipids and ω3 fatty acids. A total of 217 glycerolipid molecular species were identified, and the most abundant species included monogalactosyldiglyceride (C16:0/C20:5) (MGDG) and phosphatidylcholine (C16:0/C20:4) (PC). ARA was mainly distributed in PC, and EPA was mainly distributed in MGDG. Among all the fatty acid desaturases (FADs), the expressions of Δ5FAD, Δ6FAD, Δ9FAD, and Δ12FAD were up-regulated, whereas those of Δ15FAD and Δ17FAD were down-regulated. Based on these results, only a small proportion of EPA was synthesized through the ω3 pathway, while the majority of EPA was synthesized through the ω6 pathway. ARA synthesized in the ER was likely shuttled into the chloroplast by DAG and was converted into EPA by Δ17FAD.


Assuntos
Microalgas , Porphyridium , Porphyridium/genética , Porphyridium/metabolismo , Microalgas/genética , Microalgas/metabolismo , Lipidômica , Ácidos Graxos/análise , Ácidos Graxos Dessaturases/metabolismo , Ácido Eicosapentaenoico , Lipídeos de Membrana , Perfilação da Expressão Gênica , Nitrogênio/metabolismo
18.
Int J Mol Sci ; 25(2)2024 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-38255848

RESUMO

The cyanobacterial strain Cyanobacterium sp. IPPAS B-1200 isolated from Lake Balkhash is characterized by high relative amounts of myristic (30%) and myristoleic (10%) acids. The remaining fatty acids (FAs) are represented mainly by palmitic (20%) and palmitoleic (40%) acids. We expressed the genes for lysophosphatidic acid acyltransferase (LPAAT; EC 2.3.1.51) and Δ9 fatty acid desaturase (FAD; EC 1.14.19.1) from Cyanobacterium sp. IPPAS B-1200 in Synechococcus elongatus PCC 7942, which synthesizes myristic and myristoleic acids at the level of 0.5-1% and produces mainly palmitic (~60%) and palmitoleic (35%) acids. S. elongatus cells that expressed foreign LPAAT synthesized myristic acid at 26%, but did not produce myristoleic acid, suggesting that Δ9-FAD of S. elongatus cannot desaturate FAs with chain lengths less than C16. Synechococcus cells that co-expressed LPAAT and Δ9-FAD of Cyanobacterium synthesized up to 45% palmitoleic and 9% myristoleic acid, suggesting that Δ9-FAD of Cyanobacterium is capable of desaturating saturated acyl chains of any length.


Assuntos
Ácidos Graxos Dessaturases , Ácidos Graxos Monoinsaturados , Estearoil-CoA Dessaturase , Aciltransferases/genética , Ácidos Graxos
19.
Plant Cell Physiol ; 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37971406

RESUMO

Plant oils represent a large group of neutral lipids with important applications in food, feed and oleochemical industries. Most plants accumulate oils in the form of triacylglycerol within seeds and their surrounding tissues, which is comprised of three fatty acids attached to a glycerol backbone. Different plant species accumulate unique fatty acids in their oils, serving a range of applications in pharmaceuticals and oleochemicals. To enable the production of these distinctive oils, select plant species have evolved specialized oil metabolism pathways, involving differential gene co-expression networks and structurally divergent enzymes/proteins. Here, we summarize some of the recent advances in our understanding of oil biosynthesis in plants. We compare expression patterns of oil metabolism genes from representative species, including Arabidopsis thaliana, Ricinus communis (castor bean), Linum usitatissimum L. (flax), and Elaeis guineensis (oil palm) to showcase the co-expression networks of relevant genes for acyl metabolism. We also review several divergent enzymes/proteins associated with key catalytic steps of unique oil accumulation, including fatty acid desaturases, diacylglycerol acyltransferases, and oleosins, highlighting their structural features and preference towards unique lipid substrates. Lastly, we briefly discuss protein interactomes and substrate channeling for oil biosynthesis and the complex regulation of these processes.

20.
Genes (Basel) ; 14(10)2023 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-37895247

RESUMO

Perilla is a key component of Korean food. It contains several plant-specialized metabolites that provide medical benefits. In response to an increased interest in healthy supplement food from the public, people are focusing on the properties of Perilla. Nevertheless, unlike rice and soybeans, there are few studies based on molecular genetics on Perilla, so it is difficult to systematically study the molecular breed. The wild Perilla, Perilla citriodora 'Jeju17', was identified a decade ago on the Korean island of Jeju. Using short-reads, long-reads, and Hi-C, a chromosome-scale genome spanning 676 Mbp, with high contiguity, was assembled. Aligning the 'Jeju17' genome to the 'PC002' Chinese species revealed significant collinearity with respect to the total length. A total of 31,769 coding sequences were predicted, among which 3331 were 'Jeju17'-specific. Gene enrichment of the species-specific gene repertoire highlighted environment adaptation, fatty acid metabolism, and plant-specialized metabolite biosynthesis. Using a homology-based approach, genes involved in fatty acid and lipid triacylglycerol biosynthesis were identified. A total of 22 fatty acid desaturases were found and comprehensively characterized. Expression of the FAD genes in 'Jeju17' was examined at the seed level, and hormone signaling factors were identified. The results showed that the expression of FAD genes in 'Jeju17' at the seed level was high 25 days after flowering, and their responses of hormones and stress were mainly associated with hormone signal transduction and abiotic stress via cis-elements patterns. This study presents a chromosome-level genome assembly of P. citriodora 'Jeju17', the first wild Perilla to be sequenced from the Korean island of Jeju. The analyses provided can be useful in designing ALA-enhanced Perilla genotypes in the future.


Assuntos
Perilla , Humanos , Perilla/genética , Perilla/metabolismo , Ácidos Graxos/genética , Ácidos Graxos/metabolismo , Melhoramento Vegetal , Hormônios , República da Coreia
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