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Challenge concept to measure diet related health

OGTT  diabetes. Recovery heart rate  physical fitness. lipid load. resistance (vaccination). exercise . Challenge concept to measure diet related health. Perturbation of homeostasis to reveal health and resistance . 1 st NuGO metabolomics meeting, Reading, 4 July 2005.

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Challenge concept to measure diet related health

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  1. OGTT  diabetes Recovery heart rate  physical fitness lipid load resistance (vaccination) exercise Challenge concept to measure diet related health Perturbation of homeostasis to reveal health and resistance

  2. 1st NuGO metabolomics meeting, Reading, 4 July 2005

  3. Hanni`s examples • Fasting • OGTT • Meal • Lipid tolerance test • Physical exercise other examples • Inflammation challenge test • Vaccination • Mental stress test

  4. metabolic challenge: glucose tolerance test (OGTT)

  5. Physical challenge en resistance (Nieman, Curr Sports Med Rep, 2003)

  6. Cortisol CRP 1000 3.00 Placebo Placebo Supplement Supplement 2.50 800 2.00 Neutrophils IL-10 600 CRP (ng/ml) Cortisol (nmol/L) 14.00 75.00 1.50 Placebo Placebo 400 Supplement Supplement 12.00 1.00 60.00 10.00 200 0.50 8.00 45.00 cell count (10^6/ml) IL-10 (pg/ml) 0.00 0 6.00 30.00 T0 T2 T0 T1 T2 T3 4.00 15.00 2.00 0.00 0.00 T0 T1 T2 T3 T0 T2 Effects of challenge on immune parameters * * * * * * * * *

  7. vaccination as challenge vaccination vaccination vaccination DTH DTH days: 1 3 43 57 71 85 INTERVENTION anti-hepatitis B antibodies anti-hepatitis B antibodies anti-hepatitis B antibodies CLA in PBMC ex vivo immune function parameters CLA in PBMC ex vivo immune function parameters Treatment: CLA 50:50 fatty acids

  8. Anti-inflammatory effects of supplement mixPostprandial challenge – high fat challenge 5 weeks 5 weeks placebo Anti-inflammatory food mix N=18 Anti-inflammatory food mix placebo N=18 High fat challenge minutes 0 30 60 120 360 180 240 • 500ml high fat dairy shake (706kcal) • 21g protein (12en%), • 46g fat (59en%) (27g saturated fat) • 42g carbohydrates (30en%)

  9. Metabolites and proteins that respond differentially between AIDM and placebo in response to PPCT

  10. An inflammation challenge test: LPS The effect of moderate alcohol consumption on a human in vivo model of low-grade systemic inflammation in young, normal-weight men • 24 young men (21-40 yr) with BMI 18-27 kg/m2 • moderate alcohol (30 g/day) versus placebo • In vivo LPS challenge with low dose (0.06 ng/kg) 4 weeks 4 weeks orange juice orange juice + wodka orange juice + wodka orange juice LPS challenge LPS challenge In vivo LPS challenge: blood samples taken at 0-1-2-3-4-5-6 hours after LPS infusion

  11. MIP-1alpha: response in vitro >1000 fold induction * * * ANOVA pvalue 0.0001 mean -LPS values ~14 pg/ml MIP-1alpha: response in vivo ANOVA pvalue 0.0508 Max induction ~ 2-fold *

  12. Key questions for group discussion: What could be a “gold standard” challenge to be able to assess phenotype specific alterations in metabolic response? • What are the key processes & changes that we need to look for? • Challenging functional modules? • Metabokinetics? • How ‘individual’ do we want / need to go? • What “thinking tools” do we need? What metabolic challenges and related metabolomics analysis need to be developed and standardized in the next 3 years? • What is the best way to compete / collaborate? • Where do we get the funds?

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