Summary Prevention 8 - Nutrigenomics and prevention of chronic disease

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Summary - Prevention 8 - Nutrigenomics and prevention of chronic disease

  • 1 Introduction

  • Systems biology in human intervention studies?

    Transcriptomics, proteomics (plasma proteins), metabolomics (plasma, urine,  muscle, adipose;), classical biomarker panel (OGTT, OLTT, IR, oxidative stress, inflammation, etc

  • Metabolic syndrome

    Obesity, atherosclerosis, diabetes 2, dyslipidemia, hypertension, heart diseases;


    H - TG, abdominal obesity, hyperinsulinemia, less glucose tolerance, H - fasting glucose, L -HDL, hypertension;


    Inflammation of adipose tissue --> arrival of macrophages 

    (higher weight = worse inflammation)

    --> adipose tissue secretes cytokines -->proinflammatory and proatherogenic mediators --> sectretion of those leads to insulin resistance, atherosclerotic plaque formation


  • Problems with showing effect in intervention trials

    Interactions between ingredients/nutrients, multiple target tissues, subtle and long term effects, multiple mechanisms, interindividual variation;


    Integration of omics technologies into nutrition research.

    Measurements --> Analysis --> Interpretation --> biomarkers, pathways, system knowledge

  • 2 Nutrigenomics - Use of different testing techniques

    1. onset of disease/effect => changes in pathway dynamics to maintain homeostasis
    2. early biomarkers of the disease/effect => PROGNOSTIC MARKERS
    3. late biomarkers of the disease/effect => DIAGNOSTIC MARKERS


    ==> through the whole process, fingerprints aremandatory (for biomarkers to be useful)

  • 3 AIDM = Anti-Inflammatory Dietary Mix

    • supplemented mix
    • designed to exert effect on different inflammatory pathways 1


  • How to measure inflammation?

    There is no one golden standard for nutritional modulation of inflammation.-

    Known ionflammatory biomarkers are elevated in diseased state (CRP, adiponectin, cytokines;)


    => omics approach: measure broad range of genes, proteins and metabolites to assess inflammatory modulation and mechanisms of this process 

  • Summary of the results

    • in homeostatic condition (fasting blood samples), modulation of inflammation by the supplement mix was observed by small but significant changes in a number of inflammatory markers
    • next step: integrate these results with changes in gene expression and plasma metabolites


  • Effect on inflammation: integration of genes, proteins and metzabolites

    • omics approach: measure and include as many relevant parameters and construct an overview or network of effects related to inflammation (based on pathway enrichment tools, literature and public databases)


    • adiponectin changes indicates effect in adipose tissue: reflected by gene and protein changes
    • metabolome data indicate effect on eicosanoid related inflammation, supported by changes in gene expression in adipose tissue
    • effect on endothelial inflammation and plaque formation


    • integration of profiles of inflammatory proteins with gene and metabolite data, gives more insight into modulation of inflammation, network behind the profiles of known markers
    • INFLAMMATION MARKERS - inflammatory stress
    • METABOLISM MARKERS - metabolic stress 
    • OXIDATION MARKERS - oxidative stress
  • Conclusions

    • integrated measures describing pathways may provide stronger evidence of long-term health benefit
    • challenge tests appear more sensitive to small effects on underlying physiological processes in healthy subjects
    • individual responses to a nutritional intervention should be taken into account
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