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

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

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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

An Exploris 240 for Metabolomics
适用于代谢组学的 Exploris 240
  • 批准号:
    10412402
  • 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:
    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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