The Effects of Nitrate/Nitrite and Conjugated Linoleic Acid Supplementation on the Obese Asthmatic Pathology
硝酸盐/亚硝酸盐和共轭亚油酸补充剂对肥胖哮喘病理的影响
基本信息
- 批准号:9180182
- 负责人:
- 金额:$ 19.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-06-15 至 2018-05-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdipocytesAdultAmerican dietAnimal ModelAnimalsAnti-Inflammatory AgentsAnti-inflammatoryArea Under CurveArginineAsthmaBiological AvailabilityBiological MarkersBody CompositionBody mass indexBreathingBronchodilator AgentsCD4 Positive T LymphocytesCardiovascular DiseasesCardiovascular PhysiologyCell Culture TechniquesChronicClinicalClinical MarkersClinical ResearchComorbidityConjugated Linoleic AcidsDairy ProductsDiastolic blood pressureDietDietary SupplementationDiseaseDoseDrug CompoundingEnvironmentEnzymesEpidemiologic StudiesEpithelialExhalationExtrinsic asthmaFDA approvedFatty AcidsForced expiratory volume functionHelper-Inducer T-LymphocyteHomologous GeneHumanHuman VolunteersImmune responseIndividualInfarctionInflammationInflammatoryInjuryIntegrative MedicineInterventionInvestigational DrugsLabelLeptinLinkLungMeasuresMeatMediatingMediator of activation proteinMetabolicMetabolic DiseasesMetabolic syndromeMetabolismMitochondriaModelingNBL1 geneNOS2A geneNitratesNitric OxideNitric Oxide SynthaseNitritesNitrogen OxidesObesityOleic AcidsOutcomeOverweightOxidative StressPathologyPathway interactionsPhase I Clinical TrialsPhenotypePilot ProjectsPlaguePlasmaPost-Translational Protein ProcessingProductionPropertyProteinsPublishingPulmonary Function Test/Forced Expiratory Volume 1Quality of lifeQuestionnairesReactionReportingRespiratory Signs and SymptomsRespiratory physiologyRiskRuminantsSafetySchemeSeveritiesSignal TransductionSteroidsStructureSuperoxidesSupplementationSymptomsTestingTranscription Regulatory ProteinTransferaseUnsaturated Fatty AcidsUrineVital capacityadipokinesairway hyperresponsivenessairway inflammationasthmaticchemokinecytokinedietary constituentdietary supplementshealth care service utilizationimprovedinflammatory markerinsulin sensitivitymethacholinenitrationnitroalkenenitrogen dioxide radicalnitrosative stressnitrosyl hemoglobinnovel strategiesnovel therapeuticspi bondpre-clinicalresponsesafety study
项目摘要
Obesity is an asthma comorbidity associated with increased exacerbation rates and greater healthcare
utilization by mechanisms that are not explained by increases in Type 2 helper T cell (Th2)-related biomarkers
of airway inflammation associated with atopic asthma. In addition to an altered immune response in the lung
(Th1/Th17) obese asthmatics are also plagued by the low-grade, chronic, systemic inflammation attributed to
adipocyte secretion of pro-inflammatory chemokines and cytokines. Also contributing to systemic inflammation
is the uncoupling of nitric oxide synthase (NOS) by the arginine (Arg) metabolite, asymmetric dimethyl arginine
(ADMA). Low Arg/ADMA ratios are correlated with increasing body mass index and the resulting lower
fractional exhaled nitric oxide (FeNO). NOS uncoupling leads to low nitric oxide bioavailability and an increase
in superoxide anion production, thus contributing to the overall oxidative environment. The objective of this
study is to characterize the effects of the dietary supplements nitrate (NO3-) and nitrite (NO2-) (NOx) and
conjugated linoleic acid (cLA) on airway hyperresponsiveness and inflammation in obese asthmatics.
Epidemiological and clinical studies using NOx or cLA (individually) supplementations have reported on their
benefits in relation to disease pathologies including cardiovascular disease and metabolic disorder. A recent
pilot study we conducted demonstrated the formation of the electrophilic fatty acid, nitro-cLA (NO2-cLA) from
NOx + cLA supplementation in healthy subjects at concentrations ~3X endogenous basal levels. Importantly,
these levels are within a dose range that exerts systemic effects in preclinical animal models. This occurs
because nitroalkene fatty acids mediate anti-inflammatory signaling actions via post translational modification
of key transcriptional regulatory proteins and enzymes. These effects have been demonstrated with NO2-cLA
in animal and cell culture models and safety has been demonstrated using a synthetic homolog nitro-oleic acid
in FDA-approved phase 1 clinical trials. Since the individual dietary constituents NO3-, NO2-, and cLA are all
associated with decreased risk of metabolic syndrome symptoms and NO2-cLA is a modulator of inflammation,
it is hypothesized that obese asthmatics treated with NO3- + NO2- (NOx) + cLA will manifest improved
FeNO and reduced airway hyperresponsiveness and inflammation. This hypothesis will be tested by
pursuing two Specific Aims: Aim 1: Improve airway .NO bioavailability and airway hyperresponsiveness with
NOx + cLA treatment. Aim 2: Determine if NOx + cLA reduce the systemic and airway inflammation that
contributes to the obese asthmatic phenotype. FeNO and nitrosyl hemoglobin, inflammatory cytokines and
chemokines, NO2-cLA, and markers of oxidative stress will be measured as well as clinical markers of asthma
including airway hyperresponsiveness and the asthma control test. Positive clinical outcomes using NOx + cLA
dietary supplementation provides a complementary and integrative health intervention as well as a novel
therapeutic strategy for targeting the obese asthmatic pathology.
肥胖是一种哮喘合并症,与加重率和更大的医疗保健有关
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Stacy Lynn Gelhaus其他文献
Stacy Lynn Gelhaus的其他文献
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{{ truncateString('Stacy Lynn Gelhaus', 18)}}的其他基金
LIMA: Lipid anti-Inflammatory Mediators in Asthma to reduce airway hyperresponsiveness in obese asthmatics
LIMA:哮喘中的脂质抗炎介质可减少肥胖哮喘患者的气道高反应性
- 批准号:
10369934 - 财政年份:2022
- 资助金额:
$ 19.25万 - 项目类别:
LIMA: Lipid anti-Inflammatory Mediators in Asthma to reduce airway hyperresponsiveness in obese asthmatics
LIMA:哮喘中的脂质抗炎介质可减少肥胖哮喘患者的气道高反应性
- 批准号:
10720482 - 财政年份:2022
- 资助金额:
$ 19.25万 - 项目类别:
The Effects of Nitrate/Nitrite and Conjugated Linoleic Acid Supplementation on the Obese Asthmatic Pathology
硝酸盐/亚硝酸盐和共轭亚油酸补充剂对肥胖哮喘病理的影响
- 批准号:
9297207 - 财政年份:2016
- 资助金额:
$ 19.25万 - 项目类别:
Defining PAH-mediated carcinogenesis in lung: CYP metabolism and B[a]P transport
定义 PAH 介导的肺癌致癌作用:CYP 代谢和 B[a]P 转运
- 批准号:
7502209 - 财政年份:2007
- 资助金额:
$ 19.25万 - 项目类别:
Defining PAH-mediated carcinogenesis in lung: CYP metabolism and B[a]P transport
定义 PAH 介导的肺癌致癌作用:CYP 代谢和 B[a]P 转运
- 批准号:
7679487 - 财政年份:2007
- 资助金额:
$ 19.25万 - 项目类别:
Defining PAH-mediated carcinogenesis in lung: CYP metabolism and B[a]P transport
定义 PAH 介导的肺癌致癌作用:CYP 代谢和 B[a]P 转运
- 批准号:
7406263 - 财政年份:2007
- 资助金额:
$ 19.25万 - 项目类别:
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