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1.
Cell ; 187(5): 1177-1190.e18, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38366593

RESUMO

Phospholipids containing a single polyunsaturated fatty acyl tail (PL-PUFA1s) are considered the driving force behind ferroptosis, whereas phospholipids with diacyl-PUFA tails (PL-PUFA2s) have been rarely characterized. Dietary lipids modulate ferroptosis, but the mechanisms governing lipid metabolism and ferroptosis sensitivity are not well understood. Our research revealed a significant accumulation of diacyl-PUFA phosphatidylcholines (PC-PUFA2s) following fatty acid or phospholipid treatments, correlating with cancer cell sensitivity to ferroptosis. Depletion of PC-PUFA2s occurred in aging and Huntington's disease brain tissue, linking it to ferroptosis. Notably, PC-PUFA2s interacted with the mitochondrial electron transport chain, generating reactive oxygen species (ROS) for initiating lipid peroxidation. Mitochondria-targeted antioxidants protected cells from PC-PUFA2-induced mitochondrial ROS (mtROS), lipid peroxidation, and cell death. These findings reveal a critical role for PC-PUFA2s in controlling mitochondria homeostasis and ferroptosis in various contexts and explain the ferroptosis-modulating mechanisms of free fatty acids. PC-PUFA2s may serve as diagnostic and therapeutic targets for modulating ferroptosis.


Assuntos
Gorduras na Dieta , Ferroptose , Fosfolipídeos , Ácidos Graxos , Fosfatidilcolinas , Fosfolipídeos/química , Fosfolipídeos/metabolismo , Espécies Reativas de Oxigênio , Gorduras na Dieta/metabolismo
2.
J Biol Chem ; : 107955, 2024 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-39491650

RESUMO

Glutamate is the main excitatory transmitter in the mammalian central nervous system; glutamate transporters keep the synaptic glutamate concentrations at bay for normal brain function. Arachidonic acid (AA), docosahexaenoic acid (DHA), and other unsaturated fatty acids modulate glutamate transporters in cell- and tissue slices-based studies. Here, we investigated their effect and mechanism using a purified archaeal glutamate transporter homolog reconstituted into the lipid membranes. AA, DHA, and related fatty acids irreversibly inhibited the sodium-dependent concentrative substrate uptake into lipid vesicles within the physiologically relevant concentration range. In contrast, AA did not inhibit amino acid exchange across the membrane. The length and unsaturation of the aliphatic tail affect inhibition, and the free carboxylic headgroup is necessary. The inhibition potency did not correlate with the fatty acid effects on the bilayer deformation energies. AA does not affect the conformational dynamics of the protein, suggesting it does not inhibit structural transitions necessary for transport. Single-transporter and membrane voltage assays showed that AA and related fatty acids mediate cation leak, dissipating the driving sodium gradient. Thus, such fatty acids can act as cation ionophores, suggesting a general modulatory mechanism of membrane channels and ion-coupled transporters.

3.
Proc Natl Acad Sci U S A ; 119(30): e2122158119, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35858418

RESUMO

Eicosapentaenoic acid (EPA), an omega-3 (ω-3) polyunsaturated fatty acid, is an essential nutrient that exhibits antiinflammatory, neuroprotective, and cardiovascular-protective activities. Although EPA is used as a nutrient-based pharmaceutical agent or dietary supplement, its molecular target(s) is debatable. Here, we showed that EPA and its metabolites strongly and reversibly inhibit vesicular nucleotide transporter (VNUT), a key molecule for vesicular storage and release of adenosine triphosphate (ATP) in purinergic chemical transmission. In vitro analysis showed that EPA inhibits human VNUT-mediated ATP uptake at a half-maximal inhibitory concentration (IC50) of 67 nM, acting as an allosteric modulator through competition with Cl-. EPA impaired vesicular ATP release from neurons without affecting the vesicular release of other neurotransmitters. In vivo, VNUT-/- mice showed a delay in the onset of neuropathic pain and resistance to both neuropathic and inflammatory pain. EPA potently attenuated neuropathic and inflammatory pain in wild-type mice but not in VNUT-/- mice without affecting the basal nociception. The analgesic effect of EPA was canceled by the intrathecal injection of purinoceptor agonists and was stronger than that of existing drugs used for neuropathic pain treatment, with few side effects. Neuropathic pain impaired insulin sensitivity in previous studies, which was improved by EPA in the wild-type mice but not in the VNUT-/- mice. Our results showed that VNUT is a molecular target of EPA that attenuates neuropathic and inflammatory pain and insulin resistance. EPA may represent a unique nutrient-based treatment and prevention strategy for neurological, immunological, and metabolic diseases by targeting purinergic chemical transmission.


Assuntos
Ácido Eicosapentaenoico , Neuralgia , Proteínas de Transporte de Nucleotídeos , Trifosfato de Adenosina/metabolismo , Animais , Ácido Eicosapentaenoico/farmacologia , Ácido Eicosapentaenoico/uso terapêutico , Humanos , Resistência à Insulina , Camundongos , Neuralgia/tratamento farmacológico , Neuralgia/genética , Nociceptividade , Proteínas de Transporte de Nucleotídeos/antagonistas & inibidores , Proteínas de Transporte de Nucleotídeos/genética , Proteínas de Transporte de Nucleotídeos/metabolismo
4.
Artigo em Inglês | MEDLINE | ID: mdl-39362350

RESUMO

Obesity and hormonal dysregulation, common comorbidities of asthma, not only influence asthma risk and onset but can also complicate its management. The pathobiological characteristics of obesity, such as insulin resistance and metabolism alterations, can impact lung function and airway inflammation while highlighting potential opportunities for therapeutic intervention. Likewise, obesity alters immune cell phenotypes and corticosteroid pharmacokinetics. Hormones such as sex hormones, incretins, and thyroid hormones can also affect asthma. This review highlights the mechanisms underlying obesity-related asthma and hormonal pathologies while exploring potential therapeutic strategies and the need for more research and innovative approaches in managing these comorbid conditions.

5.
J Lipid Res ; 65(1): 100492, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38135255

RESUMO

Quantitative information on blood metabolites can be used in developing advanced medical strategies such as early detection and prevention of disease. Monitoring bioactive lipids such as steroids, bile acids, and PUFA metabolites could be a valuable indicator of health status. However, a method for simultaneously measuring these bioactive lipids has not yet been developed. Here, we report a LC/MS/MS method that can simultaneously measure 144 bioactive lipids, including steroids, bile acids, and PUFA metabolites, from human plasma, and a sample preparation method for these targets. Protein removal by methanol precipitation and purification of bioactive lipids by solid-phase extraction improved the recovery of the targeted compounds in human plasma samples, demonstrating the importance of sample preparation methods for a wide range of bioactive lipid analyses. Using the developed method, we studied the plasma from healthy human volunteers and confirmed the presence of bioactive lipid molecules associated with sex differences and circadian rhythms. The developed method of bioactive lipid analysis can be applied to health monitoring and disease biomarker discovery in precision medicine.


Assuntos
Esteroides , Espectrometria de Massas em Tandem , Humanos , Feminino , Masculino , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Ácidos e Sais Biliares , Lipídeos
6.
J Lipid Res ; 65(6): 100548, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38649096

RESUMO

DHA is abundant in the brain where it regulates cell survival, neurogenesis, and neuroinflammation. DHA can be obtained from the diet or synthesized from alpha-linolenic acid (ALA; 18:3n-3) via a series of desaturation and elongation reactions occurring in the liver. Tracer studies suggest that dietary DHA can downregulate its own synthesis, but the mechanism remains undetermined and is the primary objective of this manuscript. First, we show by tracing 13C content (δ13C) of DHA via compound-specific isotope analysis, that following low dietary DHA, the brain receives DHA synthesized from ALA. We then show that dietary DHA increases mouse liver and serum EPA, which is dependant on ALA. Furthermore, by compound-specific isotope analysis we demonstrate that the source of increased EPA is slowed EPA metabolism, not increased DHA retroconversion as previously assumed. DHA feeding alone or with ALA lowered liver elongation of very long chain (ELOVL2, EPA elongation) enzyme activity despite no change in protein content. To further evaluate the role of ELOVL2, a liver-specific Elovl2 KO was generated showing that DHA feeding in the presence or absence of a functional liver ELOVL2 yields similar results. An enzyme competition assay for EPA elongation suggests both uncompetitive and noncompetitive inhibition by DHA depending on DHA levels. To translate our findings, we show that DHA supplementation in men and women increases EPA levels in a manner dependent on a SNP (rs953413) in the ELOVL2 gene. In conclusion, we identify a novel feedback inhibition pathway where dietary DHA downregulates its liver synthesis by inhibiting EPA elongation.


Assuntos
Ácidos Docosa-Hexaenoicos , Regulação para Baixo , Ácido Eicosapentaenoico , Fígado , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Docosa-Hexaenoicos/administração & dosagem , Animais , Ácido Eicosapentaenoico/farmacologia , Ácido Eicosapentaenoico/metabolismo , Fígado/metabolismo , Fígado/efeitos dos fármacos , Camundongos , Regulação para Baixo/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Ácido alfa-Linolênico/farmacologia , Ácido alfa-Linolênico/metabolismo , Ácido alfa-Linolênico/administração & dosagem
7.
J Lipid Res ; 65(10): 100638, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39218219

RESUMO

Fatty acid desaturase (FADS1) variant-rs174550 strongly regulates polyunsaturated fatty acid (PUFA) biosynthesis. Additionally, the FADS1 is related to mitochondrial function. Thus, we investigated whether changes in mitochondrial function are associated with the genetic variation in FADS1 (rs174550) in human adipocytes isolated from individuals consuming diets enriched with either dietary alpha-linolenic (ALA) or linoleic acid (LA). Two cohorts of men homozygous for the genotype of FADS1 (rs174550) were studied: FADSDIET2 dietary intervention study with ALA- and LA-enriched diets and Kuopio Obesity Surgery study (KOBS), respectively. We could demonstrate that differentiated human adipose-derived stromal cells from subjects with the TT genotype had higher mitochondrial metabolism compared with subjects with the CC genotype of FADS1-rs174550 in the FADSDIET2. Responses to PUFA-enriched diets differed between the genotypes of FADS1-rs174550, showing that ALA, but not LA, -enriched diet stimulated mitochondrial metabolism more in subjects with the CC genotype when compared with subjects with the TT genotype. ALA, but not LA, proportion in plasma phospholipid fraction correlated positively with adipose tissue mitochondrial-DNA amount in subjects with the CC genotype of FADS1-rs174550 in the KOBS. These findings demonstrate that the FADS1-rs174550 is associated with modification in mitochondrial function in human adipocytes. Additionally, subjects with the CC genotype, when compared with the TT genotype, benefit more from the ALA-enriched diet, leading to enhanced energy metabolism in human adipocytes. Altogether, the FADS1-rs174550 could be a genetic marker to identify subjects who are most suitable to receive dietary PUFA supplementation, establishing also a personalized therapeutic strategy to improve mitochondrial function in metabolic diseases.


Assuntos
Dessaturase de Ácido Graxo Delta-5 , Ácidos Graxos Dessaturases , Mitocôndrias , Ácido alfa-Linolênico , Humanos , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Dessaturases/metabolismo , Mitocôndrias/metabolismo , Masculino , Ácido alfa-Linolênico/metabolismo , Ácido alfa-Linolênico/administração & dosagem , Ácido alfa-Linolênico/farmacologia , Adulto , Pessoa de Meia-Idade , Dieta , Genótipo , Adipócitos/metabolismo , Adipócitos/efeitos dos fármacos
8.
J Biol Chem ; 299(1): 102793, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36509140

RESUMO

Astrocytic excitatory amino acid transporter 2 (EAAT2) plays a major role in removing the excitatory neurotransmitter L-glutamate (L-Glu) from synaptic clefts in the forebrain to prevent excitotoxicity. Polyunsaturated fatty acids such as docosahexaenoic acid (DHA, 22:6 n-3) enhance synaptic transmission, and their target molecules include EAATs. Here, we aimed to investigate the effect of DHA on EAAT2 and identify the key amino acid for DHA/EAAT2 interaction by electrophysiological recording of L-Glu-induced current in Xenopus oocytes transfected with EAATs, their chimeras, and single mutants. DHA transiently increased the amplitude of EAAT2 but tended to decrease that of excitatory amino acid transporter subtype 1 (EAAT1), another astrocytic EAAT. Single mutation of leucine (Leu) 434 to alanine (Ala) completely suppressed the augmentation by DHA, while mutation of EAAT1 Ala 435 (corresponding to EAAT2 Leu434) to Leu changed the effect from suppression to augmentation. Other polyunsaturated fatty acids (docosapentaenoic acid, eicosapentaenoic acid, arachidonic acid, and α-linolenic acid) similarly augmented the EAAT2 current and suppressed the EAAT1 current. Finally, our docking analysis suggested the most stable docking site is the lipid crevice of EAAT2, in close proximity to the L-Glu and sodium binding sites, suggesting that the DHA/Leu434 interaction might affect the elevator-like slide and/or the shapes of the other binding sites. Collectively, our results highlight a key molecular detail in the DHA-induced regulation of synaptic transmission involving EAATs.


Assuntos
Ácidos Docosa-Hexaenoicos , Transportador 2 de Aminoácido Excitatório , Transmissão Sináptica , Xenopus laevis , Ácidos Docosa-Hexaenoicos/metabolismo , Transportador 2 de Aminoácido Excitatório/genética , Transportador 2 de Aminoácido Excitatório/metabolismo , Ácido Glutâmico/metabolismo , Leucina , Mutação , Xenopus laevis/metabolismo
9.
J Biol Chem ; 299(4): 103042, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36803964

RESUMO

Hepatic stellate cells (HSCs) are liver-resident cells best known for their role in vitamin A storage under physiological conditions. Upon liver injury, HSCs activate into myofibroblast-like cells, a key process in the onset of liver fibrosis. Lipids play an important role during HSC activation. Here, we provide a comprehensive characterization of the lipidomes of primary rat HSCs during 17 days of activation in vitro. For lipidomic data interpretation, we expanded our previously described Lipid Ontology (LION) and associated web application (LION/Web) with the LION-PCA heatmap module, which generates heatmaps of the most typical LION-signatures in lipidomic datasets. Furthermore, we used LION to perform pathway analysis to determine the significant metabolic conversions in lipid pathways. Together, we identify two distinct stages of HSC activation. In the first stage, we observe a decrease of saturated phosphatidylcholine, sphingomyelin, and phosphatidic acid and an increase in phosphatidylserine and polyunsaturated bis(monoacylglycero)phosphate (BMP), a lipid class typically localized at endosomes and lysosomes. In the second activation stage, BMPs, hexosylceramides, and ether-linked phosphatidylcholines are elevated, resembling a lysosomal lipid storage disease profile. The presence of isomeric structures of BMP in HSCs was confirmed ex vivo in MS-imaging datasets of steatosed liver sections. Finally, treatment with pharmaceuticals targeting the lysosomal integrity led to cell death in primary HSCs but not in HeLa cells. In summary, our combined data suggest that lysosomes play a critical role during a two-stage activation process of HSCs.


Assuntos
Células Estreladas do Fígado , Lipidômica , Humanos , Ratos , Animais , Células Estreladas do Fígado/metabolismo , Células HeLa , Cirrose Hepática/metabolismo , Lisossomos/metabolismo , Lipídeos/fisiologia
10.
Infect Immun ; 92(10): e0029924, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39194219

RESUMO

The obligate intracellular parasite Toxoplasma gondii can infect and replicate in any warm-blooded cell tested to date, but much of our knowledge about T. gondii cell biology comes from just one host cell type: human foreskin fibroblasts (HFFs). To expand our knowledge of host-parasite lipid interactions, we studied T. gondii in intestinal epithelial cells, the first site of host-parasite contact following oral infection and the exclusive site of parasite sexual development in feline hosts. We found that highly metabolic Caco-2 cells are permissive to T. gondii growth even when treated with high levels of linoleic acid (LA), a polyunsaturated fatty acid (PUFA) that kills parasites in HFFs. Caco-2 cells appear to sequester LA away from the parasite, preventing membrane disruptions and lipotoxicity that characterize LA-induced parasite death in HFFs. Our work is an important step toward understanding host-parasite interactions in feline intestinal epithelial cells, an understudied but important cell type in the T. gondii life cycle.


Assuntos
Fibroblastos , Interações Hospedeiro-Parasita , Ácido Linoleico , Toxoplasma , Toxoplasma/crescimento & desenvolvimento , Toxoplasma/metabolismo , Ácido Linoleico/metabolismo , Ácido Linoleico/farmacologia , Humanos , Células CACO-2 , Animais , Gatos , Fibroblastos/parasitologia , Fibroblastos/metabolismo , Células Epiteliais/parasitologia , Células Epiteliais/metabolismo
11.
Neurobiol Dis ; 193: 106443, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38395315

RESUMO

The coexistence of chronic pain and depression in clinical practice places a substantial social burden and profoundly impacts in patients. Although a clear correlation exists, the underlying mechanism of comorbidity between chronic pain and depression remains elusive. Research conducted in recent decades has uncovered that soluble epoxide hydrolase, a pivotal enzyme in the metabolism of polyunsaturated fatty acids, plays a crucial role in inflammation. Interestingly, this enzyme is intricately linked to the development of both pain and depression. With this understanding, this review aims to summarize the roles of soluble epoxide hydrolase in pain, depression, and their comorbidity. Simultaneously, we will also explore the underlying mechanisms, providing guidance for future research and drug development.


Assuntos
Dor Crônica , Epóxido Hidrolases , Humanos , Epóxido Hidrolases/metabolismo , Depressão , Comorbidade , Inflamação/metabolismo
12.
Am J Kidney Dis ; 84(2): 179-194.e1, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38423161

RESUMO

RATIONALE & OBJECTIVE: Many studies have reported polyunsaturated fatty acids (PUFA) as significant predictors of cardiovascular disease, but little is known about the relationship between PUFA levels and chronic kidney disease (CKD). This study explored this relationship among individuals with and without CKD. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 73,419 participants without CKD (cohort 1) and 6,735 participants with CKD (cohort 2) in the UK Biobank Study, with PUFA levels measured between 2007 and 2010. EXPOSURE: Percentage of plasma PUFA, omega-3 fatty acid (FA), omega-6 FA, docosahexaenoic acid (DHA), and linoleic acid relative to total FA. OUTCOME: Incident CKD for cohort 1 and incident kidney failure requiring replacement therapy (KFRT) for cohort 2. ANALYTICAL APPROACH: Cox proportional hazards regression analyses, including a cause-specific competing risk model. RESULTS: In cohort 1, individuals with higher quartiles of plasma PUFA levels had healthier lifestyles and fewer comorbidities. During 841,007 person-years of follow-up (median 11.9 years), incident CKD occurred in 4.5% of participants (incidence rate, 39.1 per 10,000 person-years). For incident CKD in cohort 1, the adjusted cause-specific hazard ratios for quartiles 2, 3, and 4 were 0.83 (95% CI, 0.75-0.92), 0.85 (95% CI, 0.76-0.96), 0.71 (95% CI, 0.62-0.82), respectively, compared with quartile 1. This inverse relationship was consistently observed for all PUFA types. In cohort 2, although total PUFA levels were not associated with KFRT, higher PUFA subtype levels of DHA were associated with a lower risk of KFRT. LIMITATIONS: Observational design and limited generalizability to individuals with higher disease severity; no data on eicosapentaenoic acid. CONCLUSIONS: Among individuals without CKD, higher plasma PUFA levels and all 4 PUFA components were associated with a lower risk of incident CKD. In individuals with CKD, only the omega-3 component of PUFA, DHA, was associated with a lower risk of KFRT. PLAIN-LANGUAGE SUMMARY: Low amounts of polyunsaturated fatty acids (PUFA) in the blood are suspected of increasing the chances of heart disease, but it is not known whether the PUFA relates to kidney disease occurrence. In a large group without kidney disease in the United Kingdom, people with higher levels of PUFA in their blood tended to have a lower risk of developing kidney disease compared to those with lower PUFA levels. This relationship was consistently observed for all PUFA types. However, in the group with kidney disease, only higher levels of docosahexaenoic acid, a subtype of PUFAs, were associated with a lower risk of developing severe kidney problems that required kidney replacement therapy. These findings suggest that higher levels of PUFA, found in certain healthy fats, might protect against the development of kidney disease in the general population. As kidney function declines, only the docosahexaenoic acid, a subtype of PUFA, appears to be associated with preserved kidney function.


Assuntos
Ácidos Graxos Insaturados , Insuficiência Renal Crônica , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/epidemiologia , Ácidos Graxos Insaturados/sangue , Idoso , Adulto , Estudos de Coortes , Incidência , Reino Unido/epidemiologia , Ácidos Docosa-Hexaenoicos/sangue
13.
Int Arch Allergy Immunol ; 185(2): 124-132, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37913762

RESUMO

INTRODUCTION: The incidence of allergic rhinitis (AR) is increasing year by year, and the pathogenesis is complex, in which diet may play an important role. The role of polyunsaturated fatty acids (PUFAs) in AR is still controversial. Previous studies have looked at the effects of PUFA during pregnancy, childhood, and adolescence. In this study, we aimed to determine the association between dietary intake of PUFA and AR in adults. METHODS: We used the NHANES database from 2005 to 2006 to include a total of 4,211 adult subjects. We collected dietary PUFA intake data and information on AR. Logistic regression and restricted cubic spline models were constructed to examine the association between PUFA intake and AR in adults. The t test was used to compare daily PUFA intakes in patients with and without AR. RESULTS: In the fully adjusted model (OR: 1.016; 95% CI: 1.003; 1.028), PUFA intake was positively correlated with allergic symptoms, hay fever, and AR in adults (p < 0.05). In addition, daily PUFA intake was significantly higher in people with allergic symptoms, hay fever, and AR than in people without the disease (p < 0.01). CONCLUSIONS: Our results suggest a positive association between dietary PUFA intake and AR in adults to a certain extent. Future studies on dietary PUFA dose will provide new strategies for the prevention and treatment of allergic diseases such as AR related to non-pharmaceutical interventions.


Assuntos
Rinite Alérgica Sazonal , Rinite Alérgica , Adulto , Gravidez , Feminino , Adolescente , Humanos , Criança , Estudos Transversais , Inquéritos Nutricionais , Dieta , Rinite Alérgica/epidemiologia , Ácidos Graxos Insaturados
14.
FASEB J ; 37(9): e23151, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37585289

RESUMO

Docosahexaenoic acid (DHA) and ultra-long-chain polyunsaturated fatty acids (ULC-PUFAs) are uniquely enriched in membrane phospholipids of retinal photoreceptors. Several studies have shown that di-DHA- and ULC-PUFA-containing phospholipids in photoreceptors have an important role in maintaining normal visual function; however, the molecular mechanisms underlying the synthesis and enrichment of these unique lipids in the retina, and their specific roles in retinal function remain unclear. Long-chain acyl-coenzyme A (CoA) synthetase 6 (ACSL6) preferentially converts DHA into DHA-CoA, which is a substrate during DHA-containing lipid biosynthesis. Here, we report that Acsl6 mRNA is expressed in the inner segment of photoreceptor cells and the retinal pigment epithelial cells, and genetic deletion of ACSL6 resulted in the selective depletion of di-DHA- and ULC-PUFA-containing phospholipids, but not mono-DHA-containing phospholipids in the retina. MALDI mass spectrometry imaging (MALDI-MSI) revealed the selective distribution of di-DHA- and ULC-PUFA-containing phospholipids in the photoreceptor outer segment (OS). Electroretinogram of Acsl6-/- mice exhibited photoreceptor cell-derived visual impairment, whereas the expression levels and localization of opsin proteins were unchanged. Acsl6-/- mice exhibited an age-dependent progressive decrease of the thickness of the outer nuclear layers, whereas the inner nuclear layers and OSs were normal. These results demonstrate that ACSL6 facilitates the local enrichment of di-DHA- and ULC-PUFA-containing phospholipids in the retina, which supports normal visual function and retinal homeostasis.


Assuntos
Ácidos Docosa-Hexaenoicos , Fosfolipídeos , Camundongos , Animais , Fosfolipídeos/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Retina/metabolismo , Ácidos Graxos Insaturados/metabolismo , Ligases/análise , Ligases/metabolismo , Coenzima A Ligases/genética , Coenzima A Ligases/metabolismo
15.
Crit Rev Food Sci Nutr ; : 1-14, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39066633

RESUMO

Preterm infants, often characterized by lower birth weights and underdeveloped physiologies, necessitate specialized nutritional care. While breast milk stands as the ideal nutritional source, offering substantial energy through its fatty acid content to support the infants' growth and developmental needs, its usage might not always be feasible. Fatty acids in breast milk are critical for the development of these infants. In scenarios where breast milk is not an option, formula feeding becomes a necessary alternative. Thus, a comprehensive understanding of the fatty acid profiles in both breast milk and formulas is crucial for addressing the distinct nutritional requirements of preterm infants. This paper aims to summarize the effects of lipid composition, structure, and positioning in breast milk and formula on the growth and development of preterm infants. Furthermore, it explores recent advancements in the use of novel structural lipids in formulas, laying the groundwork for future innovations in formula design specifically catered to the needs of preterm infants.

16.
Br J Nutr ; : 1-53, 2024 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-39494601

RESUMO

The associations between circulating polyunsaturated fatty acids (PUFAs) and cardiovascular risk factors and events in healthy Asian populations have been less examined robustly compared to Western populations. This systematic review aimed to summarise current evidence on the associations between n-3 and n-6 PUFAs biomarkers and cardiovascular risk factors and events in healthy Asian populations. PubMed, Embase, Web of Science and Cochrane Library were searched for observational studies from January 2010 until August 2024. Twenty-three studies were eligible, which covered six Asian countries and included events(n=7), traditional risk factors such as blood pressure and lipids(n=4), physical signs such as arterial stiffness(n=4), non-traditional lipid markers(n=1), markers of inflammation(n=4), markers of thrombosis(n=2), and non-invasive imaging-based markers such as carotid intima media thickness(n=5). Biological sample type included plasma(n=6), serum(n=14) and erythrocyte(n=3). Higher circulating total n-3 PUFAs appeared to be associated with lower hypertension risk and specifically eicosapentaenoic acid and docosahexaenoic acid to be associated with lower myocardial infarction risk, reduction in triglycerides and inflammation. Higher circulating linoleic acid was associated with improved lipid profiles and lower inflammation. Limited evidence led to inconclusive associations between circulating n-6 PUFAs biomarkers and cardiovascular disease events and blood pressure. No consistent associations with arterial stiffness, obesity, thrombosis and imaging-based biomarkers were observed for circulating PUFAs biomarkers in Asian populations. Limited studies exist for each outcome, hence results should be interpreted with caution. More high quality and prospective studies in Asian populations are warranted. Several recommendations such as sample size justification and reporting of non-respondents rate are proposed for future studies.

17.
Biosci Biotechnol Biochem ; 88(6): 696-704, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38520162

RESUMO

We focused on the production of docosahexaenoic acid (DHA)-containing microbial lipids by Aurantiochytrium sp. using of defatted soybean (DS) as a nitrogen source. Defatted soybean is a plant biomass that could provide a sustainable supply at a low cost. Results showed that Aurantiochytrium sp. could not directly assimilate the DS as a nitrogen source but could grow well in a medium containing DS fermented with rice malt. When cultivated in a fermented DS (FDS) medium, Aurantiochytrium sp. showed vigorous growth with the addition of sufficient sulfate and chloride ions as inorganic nutrients without seawater salt. A novel isolated Aurantiochytrium sp. 6-2 showed 15.8 ± 3.4 g/L DHA productivity (in 54.8 ± 12.1 g/L total fatty acid production) in 1 L of the FDS medium. Therefore, DHA produced by Aurantiochytrium sp. using FDS enables a stable and sustainable DHA supply and could be an alternative source of natural DHA derived from fish oil.


Assuntos
Ração Animal , Ácidos Docosa-Hexaenoicos , Fermentação , Glycine max , Nitrogênio , Estramenópilas , Ácidos Docosa-Hexaenoicos/biossíntese , Ácidos Docosa-Hexaenoicos/metabolismo , Glycine max/metabolismo , Glycine max/crescimento & desenvolvimento , Nitrogênio/metabolismo , Estramenópilas/metabolismo , Estramenópilas/crescimento & desenvolvimento , Ração Animal/análise , Animais , Peixes/metabolismo , Biomassa , Meios de Cultura/química
18.
Adv Exp Med Biol ; 1461: 79-95, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39289275

RESUMO

Temperature affects a variety of cellular processes because the molecular motion of cellular constituents and the rate of biochemical reactions are sensitive to temperature changes. Thus, the adaptation to temperature is necessary to maintain cellular functions during temperature fluctuation, particularly in poikilothermic organisms. For a wide range of organisms, cellular lipid molecules play a pivotal role during thermal adaptation. Temperature changes affect the physicochemical properties of lipid molecules, resulting in the alteration of cell membrane-related functions and energy metabolism. Since the chemical structures of lipid molecules determine their physicochemical properties and cellular functions, cellular lipids, particularly fatty acid-containing lipid molecules, are remodeled as a thermal adaptation response to compensate for the effects of temperature change. In this chapter, we first introduce the structure and biosynthetic pathway of fatty acid-containing lipid molecules, such as phospholipid and triacylglycerol, followed by a description of the cellular lipid-mediated mechanisms of thermal adaptation and thermoregulatory behavior in animals.


Assuntos
Regulação da Temperatura Corporal , Metabolismo dos Lipídeos , Animais , Regulação da Temperatura Corporal/fisiologia , Metabolismo Energético , Fosfolipídeos/metabolismo , Fosfolipídeos/química , Adaptação Fisiológica/fisiologia , Ácidos Graxos/metabolismo , Ácidos Graxos/química , Triglicerídeos/metabolismo , Termotolerância/fisiologia , Temperatura
19.
Pediatr Surg Int ; 40(1): 239, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39167137

RESUMO

PURPOSE: Biliary atresia (BA) poses a persistent challenge characterized by ongoing liver inflammation and subsequent fibrosis even after the clearance of jaundice (COJ). This study aimed to evaluate the therapeutic potential of eicosapentaenoic acid (EPA) in alleviating liver inflammation and limiting fibrosis during the post-COJ phase of BA. METHODS: Among the BA patients undergoing laparoscopic Kasai portoenterostomy (lapKP) between December 2016 and October 2021, EPA (20-40 mg/kg/day) was administered orally to those whose parents consented. The study included patients from January 2014 to October 2021, classifying them into two groups: EPA-treated (Group E) and untreated (Group N). Their liver fibrosis and clinical course at 1 and 2 years post-lapKP were compared. RESULTS: Group E consisted of 25 patients, while Group N comprised 32 patients. Twenty-one patients in Group E and 25 patients in Group N achieved COJ (p = 0.74). Among jaundice-free patients at 1 and 2 years post-lapKP, Group E exhibited significantly lower M2BPGi levels and platelet counts, and Group E showed a significant reduction in Aminotransferase-to-Platelet Ratio Index (APRI) at 2 years post-lapKP. CONCLUSION: Although EPA administration did not improve COJ, it attenuated the progression of liver fibrosis during the 2 years following lapKP in jaundice-free patients. (200/200Words).


Assuntos
Atresia Biliar , Progressão da Doença , Ácido Eicosapentaenoico , Cirrose Hepática , Portoenterostomia Hepática , Humanos , Portoenterostomia Hepática/métodos , Ácido Eicosapentaenoico/uso terapêutico , Ácido Eicosapentaenoico/administração & dosagem , Masculino , Feminino , Atresia Biliar/cirurgia , Lactente , Laparoscopia/métodos , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Resultado do Tratamento , Pré-Escolar
20.
Int J Mol Sci ; 25(14)2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-39062812

RESUMO

Dietary intake of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid, EPA) exerts antiarrhythmic effects, although the mechanisms are poorly understood. Here, we investigated the possible beneficial actions of EPA on saturated fatty acid-induced changes in the L-type Ca2+ channel in cardiomyocytes. Cardiomyocytes were cultured with an oleic acid/palmitic acid mixture (OAPA) in the presence or absence of EPA. Beating rate reduction in cardiomyocytes caused by OAPA were reversed by EPA. EPA also retrieved a reduction in Cav1.2 L-type Ca2+ current, mRNA, and protein caused by OAPA. Immunocytochemical analysis revealed a distinct downregulation of the Cav1.2 channel caused by OAPA with a concomitant decrease in the phosphorylated component of a transcription factor adenosine-3',5'-cyclic monophosphate (cAMP) response element binding protein (CREB) in the nucleus, which were rescued by EPA. A free fatty acid receptor 4 (FFAR4) agonist TUG-891 reversed expression of Cav1.2 and CREB mRNA caused by OAPA, whereas an FFAR4 antagonist AH-7614 abolished the effects of EPA. Excessive reactive oxygen species (ROS) accumulation caused by OAPA decreased Cav1.2 and CREB mRNA expressions, which was reversed by an ROS scavenger. Our data suggest that EPA rescues cellular Cav1.2-Ca2+ channel decline caused by OAPA lipotoxicity and oxidative stresses via both free fatty acid receptor 4-dependent and -independent pathways.


Assuntos
Canais de Cálcio Tipo L , Ácido Eicosapentaenoico , Miócitos Cardíacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Ácido Eicosapentaenoico/farmacologia , Animais , Canais de Cálcio Tipo L/metabolismo , Canais de Cálcio Tipo L/genética , Ratos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Ácidos Graxos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células Cultivadas
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