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1.
Gene ; 893: 147899, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-37839764

RESUMO

Edible oils with high unsaturated fatty acids, particularly oleic acid, are beneficial to human health. Cotton is one of the top five oil crops in the world, but the mechanism of high-quality oil synthesis and regulatory networks in cotton are largely unclear. Here, we identified Leafy cotyledon1-like 1 (GhL1L1), a NF-YB subfamily gene that is specifically expressed during somatic embryogenesis and seed maturation in cotton. Overexpression of GhL1L1 regulates the contents of unsaturated fatty acids in cotton, especially in the seeds, which is associated with altered expression of the cotton fatty acid biosynthesis-related genes. GhL1L1 synergistically enhanced the expression of GhFAD2-1A by binding to the G-box in its promoter, leading to an increase in the content of linoleic acid. Furthermore, this activation could be enhanced by GhNF-YC2 and GhNF-YA1 by form a transcriptional complex. Collectively, these results contribute to provide new insights into the molecular mechanism of oil biosynthesis in cotton and can facilitate genetic manipulation of cotton varieties with enhanced oil content.


Assuntos
Ácidos Graxos Insaturados , Proteínas de Plantas , Humanos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ácidos Graxos Insaturados/genética , Ácidos Graxos Insaturados/metabolismo , Ácido Oleico/metabolismo , Ácido Linoleico , Sementes/genética , Sementes/metabolismo , Ácidos Graxos/genética , Ácidos Graxos/metabolismo , Óleos de Plantas , Regulação da Expressão Gênica de Plantas
2.
Molecules ; 26(24)2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34946780

RESUMO

Microalgae have a great potential for the production of healthy food and feed supplements. Their ability to convert carbon into high-value compounds and to be cultured in large scale without interfering with crop cultivation makes these photosynthetic microorganisms promising for the sustainable production of lipids. In particular, microalgae represent an alternative source of polyunsaturated fatty acids (PUFAs), whose consumption is related to various health benefits for humans and animals. In recent years, several strategies to improve PUFAs' production in microalgae have been investigated. Such strategies include selecting the best performing species and strains and the optimization of culturing conditions, with special emphasis on the different cultivation systems and the effect of different abiotic factors on PUFAs' accumulation in microalgae. Moreover, developments and results obtained through the most modern genetic and metabolic engineering techniques are described, focusing on the strategies that lead to an increased lipid production or an altered PUFAs' profile. Additionally, we provide an overview of biotechnological applications of PUFAs derived from microalgae as safe and sustainable organisms, such as aquafeed and food ingredients, and of the main techniques (and their related issues) for PUFAs' extraction and purification from microalgal biomass.


Assuntos
Aquicultura , Biomassa , Ácidos Graxos Insaturados , Engenharia Metabólica , Microalgas , Ácidos Graxos Insaturados/biossíntese , Ácidos Graxos Insaturados/genética , Microalgas/genética , Microalgas/crescimento & desenvolvimento
3.
Proc Natl Acad Sci U S A ; 117(51): 32433-32442, 2020 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-33288688

RESUMO

Ferroptosis is an iron-dependent regulated necrosis mediated by lipid peroxidation. Cancer cells survive under metabolic stress conditions by altering lipid metabolism, which may alter their sensitivity to ferroptosis. However, the association between lipid metabolism and ferroptosis is not completely understood. In this study, we found that the expression of elongation of very long-chain fatty acid protein 5 (ELOVL5) and fatty acid desaturase 1 (FADS1) is up-regulated in mesenchymal-type gastric cancer cells (GCs), leading to ferroptosis sensitization. In contrast, these enzymes are silenced by DNA methylation in intestinal-type GCs, rendering cells resistant to ferroptosis. Lipid profiling and isotope tracing analyses revealed that intestinal-type GCs are unable to generate arachidonic acid (AA) and adrenic acid (AdA) from linoleic acid. AA supplementation of intestinal-type GCs restores their sensitivity to ferroptosis. Based on these data, the polyunsaturated fatty acid (PUFA) biosynthesis pathway plays an essential role in ferroptosis; thus, this pathway potentially represents a marker for predicting the efficacy of ferroptosis-mediated cancer therapy.


Assuntos
Ácidos Graxos Insaturados/biossíntese , Ferroptose/fisiologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Ácido Araquidônico/genética , Ácido Araquidônico/metabolismo , Ácido Araquidônico/farmacologia , Carbolinas/farmacologia , Linhagem Celular Tumoral , Metilação de DNA , Dessaturase de Ácido Graxo Delta-5 , Elementos Facilitadores Genéticos , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Dessaturases/metabolismo , Elongases de Ácidos Graxos/genética , Elongases de Ácidos Graxos/metabolismo , Ácidos Graxos Insaturados/genética , Ácidos Graxos Insaturados/metabolismo , Ferroptose/efeitos dos fármacos , Ferroptose/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Metabolismo dos Lipídeos/genética , Regiões Promotoras Genéticas , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-33038834

RESUMO

COVID-19 symptoms vary from silence to rapid death, the latter mediated by both a cytokine storm and a thrombotic storm. SARS-CoV (2003) induces Cox-2, catalyzing the synthesis, from highly unsaturated fatty acids (HUFA), of eicosanoids and docosanoids that mediate both inflammation and thrombosis. HUFA balance between arachidonic acid (AA) and other HUFA is a likely determinant of net signaling to induce a healthy or runaway physiological response. AA levels are determined by a non-protein coding regulatory polymorphisms that mostly affect the expression of FADS1, located in the FADS gene cluster on chromosome 11. Major and minor haplotypes in Europeans, and a specific functional insertion-deletion (Indel), rs66698963, consistently show major differences in circulating AA (>50%) and in the balance between AA and other HUFA (47-84%) in free living humans; the indel is evolutionarily selective, probably based on diet. The pattern of fatty acid responses is fully consistent with specific genetic modulation of desaturation at the FADS1-mediated 20:3→20:4 step. Well established principles of net tissue HUFA levels indicate that the high linoleic acid and low alpha-linoleic acid in populations drive the net balance of HUFA for any individual. We predict that fast desaturators (insertion allele at rs66698963; major haplotype in Europeans) are predisposed to higher risk and pathological responses to SARS-CoV-2 could be reduced with high dose omega-3 HUFA.


Assuntos
Infecções por Coronavirus/complicações , Ácidos Graxos Insaturados/biossíntese , Inflamação/etiologia , Metabolismo dos Lipídeos/genética , Pneumonia Viral/complicações , Trombose/etiologia , Betacoronavirus/fisiologia , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/metabolismo , Dessaturase de Ácido Graxo Delta-5 , Ácidos Graxos Insaturados/genética , Predisposição Genética para Doença , Haplótipos , Humanos , Individualidade , Inflamação/epidemiologia , Inflamação/genética , Inflamação/metabolismo , Lipogênese/genética , Redes e Vias Metabólicas/genética , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/genética , Pneumonia Viral/metabolismo , Polimorfismo de Nucleotídeo Único , Fatores de Risco , SARS-CoV-2 , Trombose/epidemiologia , Trombose/genética , Trombose/metabolismo
5.
Chin J Nat Med ; 18(9): 677-683, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32928511

RESUMO

Inthomycins are polyketide antibiotics which contain a terminal carboxamide group and a triene chain. Inthomycin B (1) and its two new analogues 2 and 3 were isolated from the crude extract of Streptomyces pactum L8. Identification of the gene cluster for inthomycin biosynthesis as well as the 15N-labeled glycine incorporation into inthomycins are described. Combined with the gene deletion of the rare P450 domain in the NRPS module, a formation mechanism of carboxamide moiety in inthomycins was proposed via an oxidative release of the assembly chain assisted by the P450 domain.


Assuntos
Antibacterianos/biossíntese , Ácidos Graxos Insaturados/biossíntese , Antibacterianos/química , Antibacterianos/isolamento & purificação , Ácidos Graxos Insaturados/química , Ácidos Graxos Insaturados/genética , Ácidos Graxos Insaturados/isolamento & purificação , Genes Bacterianos , Estrutura Molecular , Família Multigênica , Oxazóis/química , Oxazóis/isolamento & purificação , Oxirredução , Streptomyces/química
6.
Plant Cell Rep ; 39(11): 1505-1516, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32804247

RESUMO

KEY MESSAGE: EgMADS21 regulates PUFA accumulation in oil palm. Oil palm (Elaeis guineensis Jacq.) is the most productive world oil crop, accounting for 36% of world plant oil production. However, the molecular mechanism of the transcriptional regulation of fatty acid accumulation and lipid synthesis in the mesocarp of oil palm by up- or downregulating the expression of genes involved in related pathways remains largely unknown. Here, an oil palm MADS-box gene, EgMADS21, was screened in a yeast one-hybrid assay using the EgDGAT2 promoter sequence as bait. EgMADS21 is preferentially expressed in early mesocarp developmental stages in oil palm fruit and presents a negative correlation with EgDGAT2 expression. The direct binding of EgMADS21 to the EgDGAT2 promoter was confirmed by electrophoretic mobility shift assay. Subsequently, transient expression of EgMADS21 in oil palm protoplasts revealed that EgMADS21 not only binds to the EgDGAT2 promoter but also negatively regulates the expression of EgDGAT2. Furthermore, EgMADS21 was stably overexpressed in transgenic oil palm embryoids by Agrobacterium-mediated transformation. In three independent transgenic lines, EgDGAT2 expression was significantly suppressed by the expression of EgMADS21. The content of linoleic acid (C18:2) in the three transgenic embryoids was significantly decreased, while that of oleic acid (C18:1) was significantly increased. Combined with the substrate preference of EgDGAT2 identified in previous research, the results demonstrate the molecular mechanism by which EgMADS21 regulates EgDGAT2 expression and ultimately affects fatty acid accumulation in the mesocarp of oil palm.


Assuntos
Arecaceae/genética , Arecaceae/metabolismo , Ácidos Graxos Insaturados/metabolismo , Proteínas de Plantas/genética , Diacilglicerol O-Aciltransferase/genética , Diacilglicerol O-Aciltransferase/metabolismo , Ácidos Graxos Insaturados/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Domínio MADS/genética , Proteínas de Domínio MADS/metabolismo , Óleo de Palmeira/metabolismo , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas , Protoplastos/metabolismo
7.
J Neurotrauma ; 37(17): 1880-1891, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32253986

RESUMO

Traumatic brain injury (TBI) is a leading cause of death and disability in persons under age 45. The hallmark secondary injury profile after TBI involves dynamic interactions between inflammatory and metabolic pathways including fatty acids. Omega-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) have been shown to provide neuroprotective benefits by minimizing neuroinflammation in rodents. These effects have been less conclusive in humans, however. We postulate genetic variants influencing PUFA metabolism in humans could contribute to these disparate findings. Therefore, we sought to (1) characterize the circulating PUFA response and (2) evaluate the impact of rs174537 on inflammation after TBI. A prospective, single-center, observational pilot study was conducted to collect blood samples from Level-1 trauma patients (N = 130) on admission and 24 h post-admission. Plasma was used to quantify PUFA levels and inflammatory cytokines. Deoxyribonucleic acid was extracted and genotyped at rs174537. Associations between PUFAs and inflammatory cytokines were analyzed for all trauma cases and stratified by race (Caucasians only), TBI (TBI: N = 47; non-TBI = 83) and rs174537 genotype (GG: N = 33, GT/TT: N = 44). Patients with TBI had higher plasma DHA levels compared with non-TBI at 24 h post-injury (p = 0.013). The SNP rs174537 was associated with both PUFA levels and inflammatory cytokines (p < 0.05). Specifically, TBI patients with GG genotype exhibited the highest plasma levels of DHA (1.33%) and interleukin-8 (121.5 ± 43.3 pg/mL), which were in turn associated with poorer outcomes. These data illustrate the impact of rs174537 on the post-TBI response. Further work is needed to ascertain how this genetic variant directly influences inflammation after trauma.


Assuntos
Lesões Encefálicas Traumáticas/sangue , Lesões Encefálicas Traumáticas/genética , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-3/genética , Mediadores da Inflamação/sangue , Aciltransferases/sangue , Adulto , Biomarcadores/sangue , Lesões Encefálicas Traumáticas/diagnóstico , Ácidos Graxos Insaturados/sangue , Ácidos Graxos Insaturados/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos
8.
Nat Commun ; 11(1): 1775, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286299

RESUMO

The increased incidence of inflammatory bowel disease (IBD) has become a global phenomenon that could be related to adoption of a Western life-style. Westernization of dietary habits is partly characterized by enrichment with the ω-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA), which entails risk for developing IBD. Glutathione peroxidase 4 (GPX4) protects against lipid peroxidation (LPO) and cell death termed ferroptosis. We report that small intestinal epithelial cells (IECs) in Crohn's disease (CD) exhibit impaired GPX4 activity and signs of LPO. PUFAs and specifically AA trigger a cytokine response of IECs which is restricted by GPX4. While GPX4 does not control AA metabolism, cytokine production is governed by similar mechanisms as ferroptosis. A PUFA-enriched Western diet triggers focal granuloma-like neutrophilic enteritis in mice that lack one allele of Gpx4 in IECs. Our study identifies dietary PUFAs as a trigger of GPX4-restricted mucosal inflammation phenocopying aspects of human CD.


Assuntos
Doença de Crohn/metabolismo , Gorduras na Dieta/efeitos adversos , Enterite/metabolismo , Ácidos Graxos Insaturados/metabolismo , Inflamação/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Adulto , Animais , Morte Celular/genética , Morte Celular/fisiologia , Doença de Crohn/genética , Enterite/etiologia , Enterite/genética , Ácidos Graxos Insaturados/genética , Feminino , Glutationa Peroxidase/metabolismo , Humanos , Inflamação/genética , Peroxidação de Lipídeos/genética , Peroxidação de Lipídeos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética
9.
Metab Eng ; 57: 63-73, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31654815

RESUMO

Soybean seeds produce oil enriched in oxidatively unstable polyunsaturated fatty acids (PUFAs) and are also a potential biotechnological platform for synthesis of oils with nutritional omega-3 PUFAs. In this study, we engineered soybeans for seed-specific expression of a barley homogentisate geranylgeranyl transferase (HGGT) transgene alone and with a soybean γ-tocopherol methyltransferase (γ-TMT) transgene. Seeds for HGGT-expressing lines had 8- to 10-fold increases in total vitamin E tocochromanols, principally as tocotrienols, with little effect on seed oil or protein concentrations. Tocochromanols were primarily in δ- and γ-forms, which were shifted largely to α- and ß-tocochromanols with γ-TMT co-expression. We tested whether oxidative stability of conventional or PUFA-enhanced soybean oil could be improved by metabolic engineering for increased vitamin E antioxidants. Selected lines were crossed with a stearidonic acid (SDA, 18:4Δ6,9,12,15)-producing line, resulting in progeny with oil enriched in SDA and α- or γ-linoleic acid (ALA, 18:3Δ9,12,15 or GLA, 18:3Δ6,9,12), from transgene segregation. Oil extracted from HGGT-expressing lines had ≥6-fold increase in free radical scavenging activity compared to controls. However, the oxidative stability index of oil from vitamin E-enhanced lines was ~15% lower than that of oil from non-engineered seeds and nearly the same or modestly increased in oil from the GLA, ALA and SDA backgrounds relative to controls. These findings show that soybean is an effective platform for producing high levels of free-radical scavenging vitamin E antioxidants, but this trait may have negative effects on oxidative stability of conventional oil or only modest improvement of the oxidative stability of PUFA-enhanced oil.


Assuntos
Ácidos Graxos Insaturados , Regulação da Expressão Gênica de Plantas , Glycine max , Engenharia Metabólica , Sementes , Vitamina E , Ácidos Graxos Insaturados/biossíntese , Ácidos Graxos Insaturados/genética , Sementes/genética , Sementes/metabolismo , Óleo de Soja/biossíntese , Óleo de Soja/genética , Glycine max/genética , Glycine max/metabolismo , Vitamina E/biossíntese , Vitamina E/genética
10.
Chin J Nat Med ; 17(12): 892-899, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31882042

RESUMO

Obesity that is highly associated with numerous metabolic diseases has become a global health issue nowdays. Plant sesterterpenoids are an important group of natural products with great potential; thus, their bioactivities deserve extensive exploration. RNA-seq analysis indicated that leucosceptroid B, a sesterterpenoid previously discovered from the glandular trichomes of Leucosceptrum canum, significantly regulated the expression of 10 genes involved in lipid metabolism in Caenorhabditis elegans. Furthermore, leucosceptroid B was found to reduce fat storage, and downregulate the expression of two stearoyl-CoA desaturase (SCD) genes fat-6 and fat-7, and a fatty acid elongase gene elo-2 in wild-type C. elegans. In addition, leucosceptroid B significantly decreased fat accumulation in both fat-6 and fat-7 mutant worms but did not affect the fat storage of fat-6; fat-7 double mutant. These findings indicated that leucosceptroid B reduced fat storage depending on the downregulated expression of fat-6, fat-7 and elo-2 and thereby inhibiting the biosynthesis of the corresponding unsaturated fatty acid. These findings provide new insights into the development and utilization of plant sesterterpenoids as potential antilipemic agents.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Ácidos Graxos Insaturados/biossíntese , Ácidos Graxos Insaturados/genética , Lamiaceae/química , Sesterterpenos/farmacologia , Tricomas/química , Animais , Caenorhabditis elegans/genética
11.
PLoS One ; 14(7): e0219465, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31291354

RESUMO

Accumulation of amyloid ß (Aß) peptides, the major component of amyloid fibrils in senile plaques, is one of the main causes of Alzheimer's disease. Docosahexaenoic acid (DHA) is a fatty acid abundant in the brain, and is reported to have protective effects against Alzheimer's disease, although the mechanistic effects of DHA against Alzheimer's pathophysiology remain unclear. Because dietary supplementation of DHA in Aß precursor protein transgenic mice ameliorates Aß pathology and behavioral deficits, we hypothesize that DHA may affect the fibrillization and deposition of Aß. Here we studied the effect of different types of fatty acids on Aß fibril formation by in vitro Aß fibrillization assay. Formation of amyloid fibrils consists of two steps, i.e., the initial nucleation phase and the following elongation phase. We found that unsaturated fatty acids, especially DHA, accelerated the formation of Aß fibrils with a unique short and curved morphology in its nucleation phase, which did not elongate further into the long and straight, mature Aß fibrils. Addition of DHA afterwards did not modify the morphology of the mature Aß(1-40) fibrils. The short and curved Aß fibrils formed in the presence of DHA did not facilitate the elongation phase of Aß fibril formation, suggesting that DHA promotes the formation of "off-pathway" conformers of Aß. Our study unravels a possible mechanism of how DHA acts protectively against the pathophysiology of Alzheimer's disease.


Assuntos
Doença de Alzheimer/genética , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Ácidos Graxos Insaturados/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Amiloide/genética , Amiloide/metabolismo , Peptídeos beta-Amiloides/química , Precursor de Proteína beta-Amiloide/metabolismo , Amiloidose/genética , Amiloidose/metabolismo , Amiloidose/patologia , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Suplementos Nutricionais , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Graxos Insaturados/metabolismo , Humanos , Camundongos , Camundongos Transgênicos , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo
12.
Front Immunol ; 10: 265, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30838002

RESUMO

Obesity, a low-grade inflammatory condition, represents a major risk factor for the development of several pathologies including colorectal cancer (CRC). Although the adipose tissue inflammatory state is now recognized as a key player in obesity-associated morbidities, the underlying biological processes are complex and not yet precisely defined. To this end, we analyzed transcriptome profiles of human visceral adipocytes from lean and obese subjects affected or not by CRC by RNA sequencing (n = 6 subjects/category), and validated selected modulated genes by real-time qPCR. We report that obesity and CRC, conditions characterized by the common denominator of inflammation, promote changes in the transcriptional program of adipocytes mostly involving pathways and biological processes linked to extracellular matrix remodeling, and metabolism of pyruvate, lipids and glucose. Interestingly, although the transcriptome of adipocytes shows several alterations that are common to both disorders, some modifications are unique under obesity (e.g., pathways associated with inflammation) and CRC (e.g., TGFß signaling and extracellular matrix remodeling) and are influenced by the body mass index (e.g., processes related to cell adhesion, angiogenesis, as well as metabolism). Indeed, cancer-induced transcriptional program is deeply affected by obesity, with adipocytes from obese individuals exhibiting a more complex response to the tumor. We also report that in vitro exposure of adipocytes to ω3 and ω6 polyunsaturated fatty acids (PUFA) endowed with either anti- or pro-inflammatory properties, respectively, modulates the expression of genes involved in processes potentially relevant to carcinogenesis, as assessed by real-time qPCR. All together our results suggest that genes involved in pyruvate, glucose and lipid metabolism, fibrosis and inflammation are central in the transcriptional reprogramming of adipocytes occurring in obese and CRC-affected individuals, as well as in their response to PUFA exposure. Moreover, our results indicate that the transcriptional program of adipocytes is strongly influenced by the BMI status in CRC subjects. The dysregulation of these interrelated processes relevant for adipocyte functions may contribute to create more favorable conditions to tumor establishment or favor tumor progression, thus linking obesity and colorectal cancer.


Assuntos
Adipócitos/fisiologia , Carcinogênese/genética , Neoplasias Colorretais/genética , Ácidos Graxos Insaturados/genética , Obesidade/genética , Transcriptoma/genética , Tecido Adiposo/fisiologia , Adulto , Idoso , Fenômenos Biológicos/genética , Índice de Massa Corporal , Ácidos Graxos Ômega-3/genética , Feminino , Humanos , Inflamação/genética , Metabolismo dos Lipídeos/genética , Masculino , Pessoa de Meia-Idade
13.
Food Chem ; 276: 700-706, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30409650

RESUMO

Basil (Ocimum basilicum) from the Lamiaceae family is among the most important medicinal plants, and its seed fatty acid (FA) composition and quantity affects its nutritional and health values. It was hypothesized basil species and geographical properties significantly affect seed FA composition and quantity, which has not been previously investigated, to our knowledge. The collected seeds of the 18 basil populations were planted in a farmer's field, and the seed saturated (palmitic and stearic) and unsaturated (oleic, linoleic, and linolenic) FA were determined. Shiraz1 (14.7%) and Mobarakeh (5.1%) had the highest and the least rates of total FA, respectively. The populations were significantly different in terms of saturated FA ranging from 10.73% (Ardestan) to 13.51% (Bid Zard). However, the seed unsaturated FA (expect linoleic acid) were not significantly different from each other (average = 87.27%). Basil species and geographical properties significantly affected basil saturated FA and just unsaturated linoleic acid.


Assuntos
Ácidos Graxos/análise , Ácidos Graxos/genética , Ocimum basilicum/química , Ocimum basilicum/genética , Sementes/química , Ácidos Graxos Insaturados/análise , Ácidos Graxos Insaturados/genética , Genótipo , Sementes/genética
14.
Metab Eng ; 49: 192-200, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30149205

RESUMO

Very long chain polyunsaturated fatty acids (VLCPUFAs) are well recognized for their health benefits in humans and animals. Here we report that identification and characterization of a gene (EhELO1) encoding the first functional ELO type elongase (3-ketoacyl-CoA synthase) in higher plants that is involved in the biosynthesis of two VLCPUFAs docosadienoic acid (DDA, 22:2n-6) and docosatrienoic acid (DTA, 22:3n-3) that possess potential health-promoting properties. Functional analysis of the gene in yeast indicated that this novel enzyme could elongate a wide range of polyunsaturated fatty acids with 18-22 carbons and effectively catalyze the biosynthesis of DDA and DTA by the sequential elongations of linoleic acid and alpha-linolenic acid, respectively. Seed-specific expression of this gene in oilseed crop Brassica carinata showed that the transgenic plants produced the level of DDA and DTA at approximately 30% of the total fatty acids in seeds, and the amount of the two fatty acids remained stable over four generations. The oilseed crop producing a high and sustained level of DDA and DTA provides an opportunity for high value agricultural products for nutritional and medical uses.


Assuntos
Brassica , Produtos Agrícolas , Ácidos Graxos Insaturados , Óleos de Plantas/metabolismo , Plantas Geneticamente Modificadas , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/biossíntese , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/genética , Brassica/genética , Brassica/metabolismo , Produtos Agrícolas/genética , Produtos Agrícolas/metabolismo , Ácidos Graxos Insaturados/biossíntese , Ácidos Graxos Insaturados/genética , Proteínas de Plantas/biossíntese , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Ranunculaceae/enzimologia , Ranunculaceae/genética
15.
Mol Aspects Med ; 64: 109-134, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29305120

RESUMO

Docosahexaenoic acid (DHA) is the most abundant n-3 polyunsaturated fatty acid in the brain where it serves to regulate several important processes and, in addition, serves as a precursor to bioactive mediators. Given that the capacity of the brain to synthesize DHA locally is appreciably low, the uptake of DHA from circulating lipid pools is essential to maintaining homeostatic levels. Although, several plasma pools have been proposed to supply the brain with DHA, recent evidence suggests non-esterified-DHA and lysophosphatidylcholine-DHA are the primary sources. The uptake of DHA into the brain appears to be regulated by a number of complementary pathways associated with the activation and metabolism of DHA, and may provide mechanisms for enrichment of DHA within the brain. Following entry into the brain, DHA is esterified into and recycled amongst membrane phospholipids contributing the distribution of DHA in brain phospholipids. During neurotransmission and following brain injury, DHA is released from membrane phospholipids and converted to bioactive mediators which regulate signaling pathways important to synaptogenesis, cell survival, and neuroinflammation, and may be relevant to treating neurological diseases. In the present review, we provide a comprehensive overview of brain DHA metabolism, encompassing many of the pathways and key enzymatic regulators governing brain DHA uptake and metabolism. In addition, we focus on the release of non-esterified DHA and subsequent production of bioactive mediators and the evidence of their proposed activity within the brain. We also provide a brief review of the evidence from post-mortem brain analyses investigating DHA levels in the context of neurological disease and mood disorder, highlighting the current disparities within the field.


Assuntos
Encéfalo/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Graxos Insaturados/metabolismo , Homeostase/genética , Animais , Transporte Biológico , Encéfalo/patologia , Ácidos Graxos Insaturados/genética , Humanos , Fosfolipídeos/metabolismo , Transdução de Sinais/genética
16.
J Neuroinflammation ; 14(1): 91, 2017 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-28446241

RESUMO

BACKGROUND: The consumption of large amounts of dietary fats is one of the most important environmental factors contributing to the development of obesity and metabolic disorders. GPR120 and GPR40 are polyunsaturated fatty acid receptors that exert a number of systemic effects that are beneficial for metabolic and inflammatory diseases. Here, we evaluate the expression and potential role of hypothalamic GPR120 and GPR40 as targets for the treatment of obesity. METHODS: Male Swiss (6-weeks old), were fed with a high fat diet (HFD, 60% of kcal from fat) for 4 weeks. Next, mice underwent stereotaxic surgery to place an indwelling cannula into the right lateral ventricle. intracerebroventricular (icv)-cannulated mice were treated twice a day for 6 days with 2.0 µL saline or GPR40 and GPR120 agonists: GW9508, TUG1197, or TUG905 (2.0 µL, 1.0 mM). Food intake and body mass were measured during the treatment period. At the end of the experiment, the hypothalamus was collected for real-time PCR analysis. RESULTS: We show that both receptors are expressed in the hypothalamus; GPR120 is primarily present in microglia, whereas GPR40 is expressed in neurons. Upon intracerebroventricular treatment, GW9508, a non-specific agonist for both receptors, reduced energy efficiency and the expression of inflammatory genes in the hypothalamus. Reducing GPR120 hypothalamic expression using a lentivirus-based approach resulted in the loss of the anti-inflammatory effect of GW9508 and increased energy efficiency. Intracerebroventricular treatment with the GPR120- and GPR40-specific agonists TUG1197 and TUG905, respectively, resulted in milder effects than those produced by GW9508. CONCLUSIONS: GPR120 and GPR40 act in concert in the hypothalamus to reduce energy efficiency and regulate the inflammation associated with obesity. The combined activation of both receptors in the hypothalamus results in better metabolic outcomes than the isolated activation of either receptor alone.


Assuntos
Metabolismo Energético/fisiologia , Ácidos Graxos Insaturados/biossíntese , Homeostase/fisiologia , Hipotálamo/metabolismo , Receptores Acoplados a Proteínas G/biossíntese , Animais , Linhagem Celular , Ácidos Graxos Insaturados/genética , Expressão Gênica , Inflamação/genética , Inflamação/metabolismo , Masculino , Camundongos , Microglia/metabolismo , Obesidade/genética , Obesidade/metabolismo , Receptores Acoplados a Proteínas G/genética
17.
Mol Biol Evol ; 34(6): 1307-1318, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28333262

RESUMO

FADS genes encode fatty acid desaturases that are important for the conversion of short chain polyunsaturated fatty acids (PUFAs) to long chain fatty acids. Prior studies indicate that the FADS genes have been subjected to strong positive selection in Africa, South Asia, Greenland, and Europe. By comparing FADS sequencing data from present-day and Bronze Age (5-3k years ago) Europeans, we identify possible targets of selection in the European population, which suggest that selection has targeted different alleles in the FADS genes in Europe than it has in South Asia or Greenland. The alleles showing the strongest changes in allele frequency since the Bronze Age show associations with expression changes and multiple lipid-related phenotypes. Furthermore, the selected alleles are associated with a decrease in linoleic acid and an increase in arachidonic and eicosapentaenoic acids among Europeans; this is an opposite effect of that observed for selected alleles in Inuit from Greenland. We show that multiple SNPs in the region affect expression levels and PUFA synthesis. Additionally, we find evidence for a gene-environment interaction influencing low-density lipoprotein (LDL) levels between alleles affecting PUFA synthesis and PUFA dietary intake: carriers of the derived allele display lower LDL cholesterol levels with a higher intake of PUFAs. We hypothesize that the selective patterns observed in Europeans were driven by a change in dietary composition of fatty acids following the transition to agriculture, resulting in a lower intake of arachidonic acid and eicosapentaenoic acid, but a higher intake of linoleic acid and α-linolenic acid.


Assuntos
Ácidos Graxos Dessaturases/genética , Ácidos Graxos/genética , Alelos , DNA Antigo/análise , Dieta , Gorduras na Dieta/metabolismo , Evolução Molecular , Ácidos Graxos Dessaturases/metabolismo , Ácidos Graxos/metabolismo , Ácidos Graxos Insaturados/genética , Frequência do Gene/genética , Interação Gene-Ambiente , Humanos , Ácido Linoleico/genética , Lipídeos/genética , Família Multigênica/genética , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Análise de Sequência de DNA , População Branca/genética
18.
J Lipid Res ; 58(1): 92-110, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27856675

RESUMO

High arachidonic acid (20:4n-6) and low n-3 PUFA levels impair the capacity of cultured human bone marrow mesenchymal stromal cells (hBMSCs) to modulate immune functions. The capacity of the hBMSCs to modify PUFA structures was found to be limited. Therefore, different PUFA supplements given to the cells resulted in very different glycerophospholipid (GPL) species profiles and substrate availability for phospholipases, which have preferences for polar head group and acyl chains when liberating PUFA precursors for production of lipid mediators. When supplemented with 20:4n-6, the cells increased prostaglandin E2 secretion. However, they elongated 20:4n-6 to the less active precursor, 22:4n-6, and also incorporated it into triacylglycerols, which may have limited the proinflammatory signaling. The n-3 PUFA precursor, 18:3n-3, had little potency to reduce the GPL 20:4n-6 content, while the eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acid supplements efficiently displaced the 20:4n-6 acyls, and created diverse GPL species substrate pools allowing attenuation of inflammatory signaling. The results emphasize the importance of choosing appropriate PUFA supplements for in vitro hBMSC expansion and suggests that for optimal function they require an exogenous fatty acid source providing 20:5n-3 and 22:6n-3 sufficiently, but 20:4n-6 moderately, which calls for specifically designed optimal PUFA supplements for the cultures.


Assuntos
Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Insaturados/metabolismo , Inflamação/metabolismo , Células-Tronco Mesenquimais/metabolismo , Fosfolipídeos/metabolismo , Ácido Araquidônico/metabolismo , Células da Medula Óssea/metabolismo , Linhagem Celular , Suplementos Nutricionais , Dinoprostona/genética , Dinoprostona/metabolismo , Ácido Eicosapentaenoico/metabolismo , Ácidos Graxos Insaturados/genética , Glicerofosfolipídeos/metabolismo , Humanos , Imunomodulação/genética , Inflamação/patologia , Espectrometria de Massas , Fosfolipídeos/genética , Triglicerídeos/metabolismo
19.
Lipids ; 49(10): 1019-31, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25119487

RESUMO

Sacha inchi (Plukenetia volubilis L., Euphorbiaceae) seed oil is rich in α-linolenic acid, a kind of n-3 fatty acids with many health benefits. To discover the mechanism underlying α-linolenic acid accumulation in sacha inchi seeds, preliminary research on sacha inchi seed development was carried out from one week after fertilization until maturity, focusing on phenology, oil content, and lipid profiles. The results suggested that the development of sacha inchi seeds from pollination to mature seed could be divided into three periods. In addition, investigations on the effect of temperature on sacha inchi seeds showed that total oil content decreased in the cool season, while unsaturated fatty acid and linolenic acid concentrations increased. In parallel, expression profiles of 17 unsaturated fatty acid related genes were characterized during seed development and the relationships between gene expression and lipid/unsaturated fatty acid accumulation were discussed.


Assuntos
Euphorbiaceae/genética , Euphorbiaceae/metabolismo , Ácidos Graxos Insaturados/biossíntese , Ácidos Graxos Insaturados/genética , Óleos de Plantas/metabolismo , Sementes/genética , Sementes/metabolismo , Euphorbiaceae/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Família Multigênica , Estações do Ano , Sementes/crescimento & desenvolvimento , Temperatura , Transcriptoma , Ácido alfa-Linolênico/biossíntese , Ácido alfa-Linolênico/genética
20.
Meat Sci ; 96(2 Pt B): 1016-24, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24084607

RESUMO

Genetic parameters were estimated for a range of meat quality traits recorded on Australian lamb meat. Data were collected from Merino and crossbred progeny of Merino, terminal and maternal meat breed sires of the Information Nucleus programme. Lambs born between 2007 and 2010 (n=8968) were slaughtered, these being the progeny of 372 sires and 5309 dams. Meat quality traits were found generally to be of moderate heritability (estimates between 0.15 and 0.30 for measures of meat tenderness, meat colour, polyunsaturated fat content, mineral content and muscle oxidative capacity), with notable exceptions of intramuscular fat (0.48), ultimate pH (0.08) and fresh meat colour a* (0.08) and b* (0.10) values. Genetic correlations between hot carcass weight and the meat quality traits were low. The genetic correlation between intramuscular fat and shear force was high (-0.62). Several measures of meat quality (fresh meat redness, retail meat redness, retail oxy/met value and iron content) appear to have potential for inclusion in meat sheep breeding objectives.


Assuntos
Cruzamento , Dieta , Carne/análise , Fenótipo , Carneiro Doméstico/genética , Tecido Adiposo/metabolismo , Animais , Austrália , Peso Corporal/genética , Cor , Gorduras na Dieta/metabolismo , Ácidos Graxos Insaturados/genética , Ácidos Graxos Insaturados/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Ferro/metabolismo , Carne/normas , Minerais/metabolismo , Valor Nutritivo , Oxirredução , Estresse Mecânico
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