RESUMO
OBJECTIVES: The Healthy Kids Community Challenge is a large-scale, centrally-coordinated, community-based intervention in Ontario, Canada that promotes healthy behaviours towards improving healthy weights among children. With the goal of exploring tools available to evaluators, we leveraged electronic medical records from primary care physicians to assess child weights prior to launch of the Healthy Kids Community Challenge. This study compares the baseline (i.e. pre-intervention) prevalence of overweight and obesity in children 1-12 years of age living within and outside Healthy Kids Community Challenge communities. DESIGN: Cross-sectional analysis of a primary care patient cohort. SETTING: Electronic Medical Record Administrative data Linked Database (EMRALD) in Ontario, Canada. PARTICIPANTS: A cohort of 19 920 Ontario children who are rostered to an EMRALD physician. Children were 1-12 years of age at a primary care visit with recorded measured height and weight, between January 1, 2014 and December 31, 2015. OUTCOME MEASURE: Overweight and obesity as determined by age- and sex-standardized body mass index using World Health Organization's Growth Standards. RESULTS: In Healthy Kids Community Challenge communities, 25.6% (95% CI 24.6-26.6%) of children had zBMI above normal (i.e. >1) compared to 26.7% (95% CI 25.9-27.5%) for children living outside of Healthy Kids Community Challenge communities. CONCLUSIONS: Despite some differences in sociodemographic characteristics, zBMI of children aged 1-12 years were similar inside and outside of Healthy Kids Community Challenge community boundaries prior to program launch.
Assuntos
Índice de Massa Corporal , Bases de Dados Factuais , Sobrepeso/epidemiologia , Obesidade Infantil/epidemiologia , Peso Corporal/fisiologia , Criança , Pré-Escolar , Estudos de Coortes , Registros Eletrônicos de Saúde , Feminino , Humanos , Lactente , Sobrepeso/fisiopatologia , Obesidade Infantil/fisiopatologia , Saúde PúblicaRESUMO
BACKGROUND: Qualitative studies have suggested that food insecurity adversely affects infant feeding practices. We aimed to determine how household food insecurity relates to breastfeeding initiation, duration of exclusive breastfeeding and vitamin D supplementation of breastfed infants in Canada. METHODS: We studied 10 450 women who had completed the Maternal Experiences - Breastfeeding Module and the Household Food Security Survey Module of the Canadian Community Health Survey (2005-2014) and who had given birth in the year of or year before their interview. We used multivariable Cox proportional hazards models and logistic regression to examine the relation between food insecurity and infant feeding practices, adjusting for sociodemographic characteristics, maternal mood disorders and diabetes mellitus. RESULTS: Overall, 17% of the women reported household food insecurity, of whom 8.6% had moderate food insecurity and 2.9% had severe food insecurity (weighted percentages). After adjustment for sociodemographic factors, women with food insecurity were no less likely than others to initiate breastfeeding or provide vitamin D supplementation to their infants. Half of the women with food insecurity ceased exclusive breastfeeding by 2 months, whereas most of those with food security persisted with breastfeeding for 4 months or more. Relative to women with food security, those with marginal, moderate and severe food insecurity had significantly lower odds of exclusive breastfeeding to 4 months, but only women with moderate food insecurity had lower odds of exclusive breastfeeding to 6 months, independent of sociodemographic characteristics (odds ratio 0.60, 95% confidence interval 0.39-0.92). Adjustment for maternal mood disorder or diabetes slightly attenuated these relationships. INTERPRETATION: Mothers caring for infants in food-insecure households attempted to follow infant feeding recommendations, but were less able than women with food security to sustain exclusive breastfeeding. Our findings highlight the need for more effective interventions to support food-insecure families with newborns.
Assuntos
Aleitamento Materno/estatística & dados numéricos , Suplementos Nutricionais/estatística & dados numéricos , Características da Família , Abastecimento de Alimentos/estatística & dados numéricos , Adulto , Canadá , Feminino , Inquéritos Epidemiológicos , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Fatores Socioeconômicos , Vitamina D/administração & dosagem , Populações VulneráveisRESUMO
OBJECTIVES: To determine the extent to which Canadian adults' food preparation and cooking skills and use of home or community gardens relate to their household food insecurity status; and to compare the food shopping and cooking behaviours of adults in food-secure and food-insecure households. METHODS: Data were drawn from two Rapid Response Modules appended to the Canadian Community Health Survey in 2012 and 2013. The analytic sample comprised 16,496 respondents 18 years and older. Multivariable logistic regression analyses were conducted to determine the association between food insecurity and adults' self-rated cooking abilities, food preparation skills score, use of gardens, food shopping behaviours, and cooking behaviours, while adjusting for socio-demographic characteristics. RESULTS: Adults in food-insecure households did not differ significantly from others with respect to their food preparation skills or cooking ability, and neither variable predicted the odds of household food insecurity when socio-demographic characteristics were taken into account. Adults in food-insecure households were less likely to use a garden for food, but gardening was unrelated to the odds of food insecurity. Shopping with a budget was more common among adults in food-insecure households, but no other differences in food shopping behaviours were observed after adjustment for socio-demographic characteristics. Adults in food-insecure households were as likely as others to adjust recipes to make them healthier, but they had higher odds of adjusting recipes to reduce their fat content. CONCLUSION: Our findings suggest that household food insecurity in Canada is not a problem of insufficient food skills.
Assuntos
Culinária , Características da Família , Manipulação de Alimentos , Abastecimento de Alimentos/estatística & dados numéricos , Jardins/estatística & dados numéricos , Adulto , Canadá , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
With technological innovation, comprehensive dietary intake data can be collected in a wide range of studies and settings. The Automated Self-Administered 24-hour (ASA24) Dietary Assessment Tool is a web-based system that guides respondents through 24-h recalls. The purpose of this paper is to describe lessons learned from five studies that assessed the feasibility and validity of ASA24 for capturing recall data among several population subgroups in Canada. These studies were conducted within a childcare setting (preschool children with reporting by parents), in public schools (children in grades 5-8; aged 10-13 years), and with community-based samples drawn from existing cohorts of adults and older adults. Themes emerged across studies regarding receptivity to completing ASA24, user experiences with the interface, and practical considerations for different populations. Overall, we found high acceptance of ASA24 among these diverse samples. However, the ASA24 interface was not intuitive for some participants, particularly young children and older adults. As well, technological challenges were encountered. These observations underscore the importance of piloting protocols using online tools, as well as consideration of the potential need for tailored resources to support study participants. Lessons gleaned can inform the effective use of technology-enabled dietary assessment tools in research.
Assuntos
Inquéritos sobre Dietas , Rememoração Mental , Sistemas On-Line , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Canadá , Criança , Pré-Escolar , Comportamento do Consumidor , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Reprodutibilidade dos Testes , AutorrelatoRESUMO
Resolvins of the D-series are specialized pro-resolving lipid mediators that regulate cellular response by orchestrating resolution networks involved in host responses to injury and infection. Here, endogenous resolvin D4 was identified in human tissues and found to persist late into the resolution phase of acute murine Staphylococcus aureus infections. Completion of the first total synthesis of resolvin D4 established the absolute stereochemical configuration of RvD4 confirmed by matching with endogenous RvD4 from resolving exudates in dorsal pouch S. aureus infections. In vivo, RvD4 (ng/mouse) reduced neutrophilic infiltration (~40%) and enhanced uptake of apoptotic PMN (51%) by human dermal fibroblasts at concentrations as low as 0.1 nM. These results establish the complete stereochemistry of RvD4 as 4S,5R,17S-trihydroxydocosa-6E,8E,10Z,13Z,15E,19Z-hexaenoic acid and its novel pro-resolving actions in S. aureus infections as well as its potent ability to stimulate clearance of apoptotic cells by skin fibroblasts.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Ácidos Docosa-Hexaenoicos/farmacologia , Peritonite/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/metabolismo , Apoptose/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/biossíntese , Ácidos Docosa-Hexaenoicos/química , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/imunologia , Interações Hospedeiro-Patógeno , Humanos , Masculino , Camundongos , Infiltração de Neutrófilos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/patologia , Peritonite/imunologia , Peritonite/microbiologia , Pele/efeitos dos fármacos , Pele/imunologia , Pele/microbiologia , Infecções Cutâneas Estafilocócicas/imunologia , Infecções Cutâneas Estafilocócicas/microbiologia , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/patogenicidadeRESUMO
Human milk contains nutrients and bioactive products relevant to infant development and immunological protection. Here, we investigated the proresolving properties of milk using human milk lipid mediator isolates (HLMIs) and determined their impact on resolution programs in vivo and with human macrophages. HLMIs reduced the maximum neutrophil numbers (14.6±1.2 × 10(6)-11.0±1.0 × 10(6) cells per exudate) and shortened the resolution interval (Ri; 50% neutrophil reduction) by 54% compared with peritonitis. Using rigorous liquid-chromatography tandem-mass spectrometry (LC-MS-MS)-based lipid mediator (LM) metabololipidomics, we demonstrated that human milk possesses a proresolving LM-specialized proresolving mediator (LM-SPM) signature profile, containing SPMs (e.g. resolvins (Rv), protectins (PDs), maresins (MaRs), and lipoxins (LXs)) at bioactive levels (pico-nanomolar concentrations) that enhanced human macrophage efferocytosis and bacterial containment. SPMs identified in human milk included D-series Rvs (e.g., RvD1, RvD2, RvD3, AT-RvD3, and RvD4), PD1, MaR1, E-series Rvs (e.g. RvE1, RvE2, and RvE3), and LXs (LXA4 and LXB4). Of the SPMs identified in human milk, RvD2 and MaR1 (50 ng per mouse) individually shortened Ri by â¼75%. Milk from mastitis gave higher leukotriene B4 and prostanoids and lower SPM levels. Taken together, these findings provide evidence that human milk has proresolving actions via comprehensive LM-SPM profiling, describing a potentially novel mechanism in maternal-infant biochemical imprinting.
Assuntos
Anti-Inflamatórios/metabolismo , Macrófagos/imunologia , Leite Humano/metabolismo , Neutrófilos/imunologia , Peritonite/imunologia , Doença Aguda , Animais , Anti-Inflamatórios/química , Apoptose , Células Cultivadas , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/química , Ácidos Docosa-Hexaenoicos/metabolismo , Humanos , Masculino , Metabolômica , Camundongos , Camundongos Endogâmicos , Leite Humano/química , Peritonite/induzido quimicamente , FagocitoseRESUMO
Neuroinflammation is a characteristic of a multitude of neurological and psychiatric disorders. Modulating inflammatory pathways offers a potential therapeutic target in these disorders. Omega-3 polyunsaturated fatty acids have anti-inflammatory and pro-resolving properties in the periphery, however, their effect on neuroinflammation is less studied. This review summarizes 61 animal studies that tested the effect of omega-3 polyunsaturated fatty acids on neuroinflammatory outcomes in vivo in various models including stroke, spinal cord injury, aging, Alzheimer's disease, Parkinson's disease, lipopolysaccharide and IL-1ß injections, diabetes, neuropathic pain, traumatic brain injury, depression, surgically induced cognitive decline, whole body irradiation, amyotrophic lateral sclerosis, N-methyl-D-aspartate-induced excitotoxicity and lupus. The evidence presented in this review suggests anti-neuroinflammatory properties of omega-3 polyunsaturated fatty acids, however, it is not clear by which mechanism omega-3 polyunsaturated fatty acids exert their effect. Future research should aim to isolate the effect of omega-3 polyunsaturated fatty acids on neuroinflammatory signaling in vivo and elucidate the mechanisms underlying these effects.
Assuntos
Ácidos Graxos Ômega-3/farmacologia , Inflamação/tratamento farmacológico , Doenças do Sistema Nervoso/tratamento farmacológico , Animais , Modelos Animais de Doenças , Ácidos Graxos Ômega-3/uso terapêutico , Humanos , Inflamação/complicações , Inflamação/metabolismo , Doenças do Sistema Nervoso/complicações , Doenças do Sistema Nervoso/metabolismoRESUMO
OBJECTIVES: Specialized proresolving lipid mediators have emerged as powerful modulators of inflammation and activators of resolution. Animal models show significant benefits of specialized proresolving lipid mediators on survival and wound healing after major burn trauma. To date, no studies have investigated specialized proresolving lipid mediators and their relation to other lipid mediator pathways in humans after trauma. Here we determine if patients with poor outcomes after trauma have dysregulated lipid mediator pathways. DESIGN: We studied blood leukocyte expression of 18 genes critical to the synthesis, signaling, and metabolism of specialized proresolving lipid mediators and proinflammatory lipid mediators, and we correlated these expression patterns with clinical outcomes in trauma patients from the Inflammation and the Host Response to Injury study. SETTING: Seven U.S. medical trauma centers. SUBJECTS: Ninety-six patients enrolled in the Inflammation and Host Response to Injury study, after blunt trauma and unambiguously classified as having uncomplicated or complicated recoveries. Twenty-eight healthy volunteers were enrolled as controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Within each patient, the 18 genes of interest were used to calculate scores for distinct families of lipid mediators, including resolvins, lipoxins, prostaglandins, and leukotrienes, as well as leukotriene to resolvin score ratios. Scores were built using a simple weighting scheme, taking into consideration both dependent and independent activities of enzymes and receptors responsible for lipid mediator biosynthesis and function. Individually, ALOX12, PTGS2, PTGES, PTGDS, ALOX5AP, LTA4H, FPR2, PTGER2, LTB4R, HPGD, PTGR1, and CYP4F3 were expressed differentially over 28 days posttrauma between patients with uncomplicated and complicated recoveries (p < 0.05). When all genes were combined into scores, patients with uncomplicated recoveries had differential and higher resolvin scores (p < 0.001) and lower leukotriene scores (p < 0.001). A final combined ratio was calculated for each patient, and posttrauma leukotriene score to resolvin score ratios were significantly lower in patients with uncomplicated clinical courses (p < 0.001). CONCLUSIONS: proresolving lipid mediator lipidomics and/or protein expression, and identifying associated therapeutic targets, may influence the clinical management of trauma patients.
Assuntos
Expressão Gênica/imunologia , Leucócitos/imunologia , Metabolismo dos Lipídeos/imunologia , Ferimentos e Lesões/imunologia , Adulto , Estado Terminal , Ácido Eicosapentaenoico/análogos & derivados , Feminino , Humanos , Inflamação/imunologia , Mediadores da Inflamação/imunologia , Unidades de Terapia Intensiva , Tempo de Internação , Leucotrienos/genética , Lipoxinas/genética , Masculino , Pessoa de Meia-Idade , Prostaglandinas/genética , Ferimentos e Lesões/mortalidadeRESUMO
Resolution of inflammation is an active process driven by several new families of endogenous lipid mediators collectively coined specialized proresolving mediators (SPM). Here, we report a synthetic analog of resolvin D1 (RvD1) and aspirin-triggered RvD1, benzo-diacetylenic-17R-RvD1-methyl ester (BDA-RvD1), which was prepared using fewer steps than required for total organic synthesis of natural SPM. BDA-RvD1 was resistant to further metabolism by human recombinant 15-prostaglandin dehydrogenase, a major inactivation pathway for RvD1. In ischemia-reperfusion-initiated second organ injury, BDA-RvD1 intravenously (1 µg) reduced neutrophil infiltration into the lungs by 58 ± 9% and was significantly more potent than native RvD1. BDA-RvD1 at 100 ng/mouse also shortened the resolution interval, Ri, of Escherichia coli peritonitis with a similar potency as RvD1, by ~57%, from Ri 10.5 h to 4.5 h. With isolated human phagocytes, BDA-RvD1 at picomolar concentrations (10(-12) M) stimulated phagocytosis of zymosan A particles. BDA-RvD1 activated human recombinant G protein-coupled receptor 32/DRV1, an RvD1 receptor, in a dose-dependent manner. These results indicate that, both in vivo in mice and with isolated human cells, BDA-RvD1 shares defining proresolving actions of RvD1, including inhibiting leukocyte infiltration and stimulating phagocytosis. Moreover, they provide evidence for a new analog mimetic and example of an immunoresolvent, namely an agent that stimulates active resolution of inflammation, for a potential new therapeutic class.
Assuntos
Ácidos Docosa-Hexaenoicos/farmacologia , Infecções por Escherichia coli/tratamento farmacológico , Ésteres/química , Peritonite/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Células Cultivadas , Ácidos Docosa-Hexaenoicos/química , Ácidos Docosa-Hexaenoicos/metabolismo , Escherichia coli/efeitos dos fármacos , Ésteres/síntese química , Humanos , Inflamação/tratamento farmacológico , Pulmão/imunologia , Pulmão/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Infiltração de Neutrófilos/efeitos dos fármacos , Fagócitos/imunologia , Fagocitose/efeitos dos fármacos , Fagocitose/imunologia , Receptores Acoplados a Proteínas G/agonistas , Traumatismo por Reperfusão/imunologia , Zimosan/imunologiaRESUMO
Docosahexaenoic acid (22:6n-3) is the major brain n-3 polyunsaturated fatty acid and it is possible that docosahexaenoic acid is anti-inflammatory in the brain as it is known to be in other tissues. Using a combination of models including the fat-1 transgenic mouse, chronic dietary n-3 polyunsaturated fatty acid modulation in transgenic and wild-type mice, and acute direct brain infusion, we demonstrated that unesterified docosahexaenoic acid attenuates neuroinflammation initiated by intracerebroventricular lipopolysaccharide. Hippocampal neuroinflammation was assessed by gene expression and immunohistochemistry. Furthermore, docosahexaenoic acid protected against lipopolysaccharide-induced neuronal loss. Acute intracerebroventricular infusion of unesterified docosahexaenoic acid or its 12/15-lipoxygenase product and precursor to protectins and resolvins, 17S-hydroperoxy-docosahexaenoic acid, mimics anti-neuroinflammatory aspects of chronically increased unesterified docosahexaenoic acid. LC-MS/MS revealed that neuroprotectin D1 and several other docosahexaenoic acid-derived specialized pro-resolving mediators are present in the hippocampus. Acute intracerebroventricular infusion of 17S-hydroperoxy-docosahexaenoic acid increases hippocampal neuroprotectin D1 levels concomitant to attenuating neuroinflammation. These results show that unesterified docosahexaenoic acid is protective in a lipopolysaccharide-initiated mouse model of acute neuroinflammation, at least in part, via its conversion to specialized pro-resolving mediators; these docosahexaenoic acid stores may provide novel targets for the prevention and treatment(s) of neurological disorders with a neuroinflammatory component. Our study shows that chronically increased brain unesterified DHA levels, but not solely phospholipid DHA levels, attenuate neuroinflammation. Similar attenuations occur with acute increases in brain unesterified DHA or 17S-HpDHA levels, highlighting the importance of an available pool of precursor unesterified DHA for the production of enzymatically derived specialized pro-resolving mediators that are critical in the regulation of neuroinflammation.
Assuntos
Anti-Inflamatórios , Ácidos Docosa-Hexaenoicos/farmacologia , Inflamação/patologia , Inflamação/prevenção & controle , Fármacos Neuroprotetores , Animais , Radioisótopos de Carbono , Dieta , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Imuno-Histoquímica , Bombas de Infusão Implantáveis , Injeções Intraventriculares , Lipopolissacarídeos/farmacologia , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos C57BL , Fosfolipídeos/metabolismoRESUMO
Neuroinflammation is present in the majority of acute and chronic neurological disorders. Excess or prolonged inflammation in the brain is thought to exacerbate neuronal damage and loss. Identifying modulators of neuroinflammation is an active area of study since it may lead to novel therapies. Omega-3 polyunsaturated fatty acids (n-3 PUFA) are anti-inflammatory in many non-neural tissues; their role in neuroinflammation is less studied. This review summarizes the relationship between n-3 PUFA and brain inflammation in animal models of brain injury and aging. Evidence by and large shows protective effects of n-3 PUFA in models of sickness behavior, stroke, aging, depression, Parkinson's disease, diabetes, and cytokine- and irradiation-induced cognitive impairments. However, rigorous studies that test the direct effects of n-3 PUFA in neuroinflammation in vivo are lacking. Future research in this area is necessary to determine if, and if so which, n-3 PUFA directly target brain inflammatory pathways. n-3 PUFA bioactive metabolites may provide novel therapeutic targets for neurological disorders with a neuroinflammatory component.
Assuntos
Envelhecimento , Anti-Inflamatórios não Esteroides/uso terapêutico , Lesões Encefálicas/dietoterapia , Modelos Animais de Doenças , Ácidos Graxos Ômega-3/uso terapêutico , Doenças Neurodegenerativas/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/metabolismo , Encéfalo/imunologia , Encéfalo/metabolismo , Lesões Encefálicas/imunologia , Lesões Encefálicas/metabolismo , Lesões Encefálicas/fisiopatologia , Suplementos Nutricionais , Ácidos Graxos Ômega-3/metabolismo , Óleos de Peixe/metabolismo , Óleos de Peixe/uso terapêutico , Humanos , Doenças Neurodegenerativas/dietoterapia , Doenças Neurodegenerativas/imunologia , Doenças Neurodegenerativas/metabolismo , Neurônios/imunologia , Neurônios/metabolismo , Fármacos Neuroprotetores/metabolismo , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/prevenção & controleRESUMO
In the brain, polyunsaturated fatty acids (PUFA), especially arachidonic acid and docosahexaenoic acid (DHA), are required for regulating membrane fluidity, neuronal survival and signal transduction. Since the brain cannot synthesize n-6 and n-3 PUFA de novo, they must be supplied from the blood. However, the methods of PUFA entry into the brain are not agreed upon. This study tested the necessity of CD36, a candidate transporter of unesterified fatty acids, for maintaining brain PUFA concentrations by comparing brain PUFA concentrations in CD36(-/-) mice to their wild-type littermates. Because CD36(-/-) mice have been reported to have impaired learning ability, the PUFA concentrations in different brain regions (cortex, hippocampus, cerebellum and the remainder of brain) were investigated. At 9 weeks of age, the brain was separated into the four regions and fatty acid concentrations in total and phospholipid classes of these brain regions were analyzed using thin layer and gas chromatography. There were no statistical differences in arachidonic acid or DHA concentrations in the different brain regions between wild-type and CD36(-/-) mice, in total or phospholipid fractions. Concentrations of monounsaturated fatty acids were decreased in several phospholipid fractions in CD36(-/-) mice. These findings suggest that CD36 is not necessary for maintaining brain PUFA concentrations and that other mechanisms must exist.
Assuntos
Encéfalo/metabolismo , Antígenos CD36/genética , Ácidos Graxos Insaturados/metabolismo , Deleção de Genes , Animais , Química Encefálica/genética , Colesterol/análise , Colesterol/metabolismo , Ácidos Graxos Insaturados/análise , Metabolismo dos Lipídeos/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Concentração OsmolarRESUMO
Fat-1 transgenic mice endogenously convert n-6 to n-3 polyunsaturated fatty acids (PUFA). The aims of this study were to test whether a) fish oil feeding can attain similar brain n-3 PUFA levels as the fat-1 mouse, and b) fat-1 mouse brain docosahexaenoic acid (22:6n-3; DHA) levels can be potentiated by fish oil feeding. Fat-1 mice and their wildtype littermates consumed either a 10% safflower oil (SO) or a 2% fish oil and 8% safflower oil chow (FO). Brain total lipid and phospholipid fraction fatty acids were analyzed using GC-FID. Wildtype mice fed FO chow had similar brain levels of DHA as fat-1 mice fed SO chow. Fat-1 mice fed FO chow had similar brain n-3 PUFA levels as fat-1 mice fed SO chow. In conclusion, brain levels of DHA in the fat-1 mouse can be obtained by and were not further augmented with fish oil feeding.
Assuntos
Encéfalo/metabolismo , Gorduras na Dieta/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Insaturados/metabolismo , Animais , Química Encefálica , Feminino , Óleos de Peixe/metabolismo , Camundongos , Camundongos Transgênicos , Óleo de Cártamo/metabolismoRESUMO
Polyunsaturated fatty acids (PUFA), especially docosahexaenoic and arachidonic acids, as well as cholesterol are important for neural development and maintaining brain function. However, in contrast to cholesterol, the brain is unable to synthesize the required amounts of these PUFA de novo and requires a constant supply from plasma. Suggested pools of uptake include plasma unesterified PUFA or the uptake of PUFA-containing lipoproteins via lipoprotein receptors into endothelial cells of the blood brain barrier. Our study tested whether the very low density lipoprotein receptor (VLDLr) is necessary for maintaining brain PUFA and cholesterol concentrations. Moreover, since VLDLr knockout (VLDLr(-/-)) mice have been reported to have behavioural deficits, this study asked the question whether altered brain PUFA and cholesterol concentrations might be related to these deficits. VLDLr(-/-) and wild-type mice had ad libitum access to chow. At 7 weeks of age the mice were sacrificed, and the cortex, cerebellum, hippocampus, and the remainder of the brain were isolated for total fatty acid and cholesterol analyses. There were no differences in total lipid PUFA or cholesterol concentrations in any of the four brain regions between VLDLr(-/-) and wild-type mice. These findings demonstrate that the VLDLr is not necessary for maintaining brain PUFA concentrations and suggest that other mechanisms to transport PUFA into the brain must exist.
Assuntos
Encéfalo/metabolismo , Ácidos Graxos Insaturados/metabolismo , Receptores de LDL/fisiologia , Animais , Ácido Araquidônico/metabolismo , Comportamento Animal , Peso Corporal/genética , Peso Corporal/fisiologia , Colesterol/metabolismo , Cromatografia Gasosa , Ácidos Docosa-Hexaenoicos/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Masculino , Camundongos , Camundongos Knockout , Receptores de LDL/genéticaRESUMO
The brain is particularly enriched in glycerophospholipids with either arachidonic or docosahexaenoic acid esterified in the stereospecifically numbered-2 position. In this paper, we review how combining a kinetic approach to study the uptake and turnover of arachidonic and docosahexaenoic acids within brain phospholipids of unanesthetized rats, along with chronic administration of antimanic drugs (lithium, valproate and carbamazepine), have advanced our understanding of how polyunsaturated fatty acids (PUFA) enter the brain, and the mechanisms that regulate their turnover within brain phospholipids. The incorporation rates of arachidonic and docosahexaenoic acid from the plasma unesterified pool into brain phospholipids closely approximate independent measures of their consumption rates by the brain, suggesting this is quantitatively the major pool for uptake of these PUFA. Antimanic drugs (lithium and carbamazepine) that downregulate the activity of the calcium-dependent cytosolic phospholipase A(2) (cPLA(2)) transcription factor AP-2, and in turn the expression and activity of cPLA(2,) lead to a selective downregulation in brain arachidonic acid turnover. Furthermore, targeting arachidonoyl-CoA formation via ordered, non-competitive inhibition of an acyl-CoA synthetase with valproate also selectively decreases brain arachidonic acid turnover. Drugs that increase brain cPLA(2) activity (N-methyl-d-aspartic acid and fluoxetine) are correlated with increased turnover of arachidonic acid in brain phospholipids. Altered PUFA metabolism has been implicated in several neurological disorders, including bipolar disorder and Alzheimer's disease. Identifying the enzymes that regulated brain PUFA metabolism could lead to new therapeutic approaches for these disorders.
Assuntos
Encéfalo/metabolismo , Ácidos Graxos Insaturados/metabolismo , Animais , Antimaníacos/metabolismo , Fosfolipases A2 do Grupo IV/metabolismo , Humanos , Modelos Biológicos , RatosRESUMO
Epidemiological studies have linked fish consumption to lower rates of neurological diseases. Fish contains high levels of omega-3 polyunsaturated fatty acids (n-3 PUFA), and several lines of evidence suggest that the n-3 PUFA docosahexaenoic acid (DHA; 22:6n-3) acts in the brain via anti-apoptotic and neurotrophic pathways. In addition, DHA may act through anti-neuroinflammatory pathways, as DHA possesses anti-inflammatory properties in the periphery. Evidence from animal models has indicated that DHA and its derivatives (resolvin D1 and protectin D1) attenuate colitis, peritonitis and ischemic stroke. n-3 PUFA deprivation in rats decreases brain levels of DHA and increases markers of the brain arachidonic acid (20:4n-6) cascade, a proinflammatory pathway. Thus, chronic low intake of n-3 PUFA may predispose the brain to weak anti-inflammatory, as well as strong proinflammatory signals. Neurological disorders, including Alzheimer's disease, Parkinson's disease and major depression, display a neuroinflammatory component. n-3 PUFA supplementation, as well as drugs targeting brain PUFA metabolism, are promising candidates in the prevention and treatment of neurological disorders.
Assuntos
Anti-Inflamatórios , Ácidos Docosa-Hexaenoicos/uso terapêutico , Neurite (Inflamação)/tratamento farmacológico , Animais , Ácido Araquidônico/metabolismo , Química Encefálica , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Graxos Insaturados/metabolismo , HumanosRESUMO
Brain phospholipids are highly enriched in docosahexaenoic acid (DHA; 22:6n-3). Recent advances indicate that 22:6n-3 is released from brain phospholipids via the action of phospholipase A2 (PLA2) in response to several stimuli, including neurotransmission, where it then acts as a secondary messenger. Furthermore, it is now known that released 22:6n-3 is a substrate for several oxygenation enzymes whose products are potent signaling molecules. One emerging candidate PLA2 involved in the release of 22:6n-3 from brain phospholipids is the group VI calcium-independent phospholipase A2 (iPLA2). After a brief review of brain 22:6n-3 metabolism, cell culture and rodent studies facilitating the hypothesis that group VI iPLA2 releases 22:6n-3 from brain phospholipids are discussed. The identification of PLA2s involved in cleaving 22:6n-3 from brain phospholipids could lead to the development of novel therapeutics for brain disorders in which 22:6n-3 signaling is disordered.