Nutrigenomics

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Nutrigenomics is the science that examines the response of individuals to food compounds using post-genomic and related technologies (e.g. genomics, transcriptomics, proteomics, metabol/nomic etc.). The long-term aim of nutrigenomics is to understand how the whole body responds to real foods using an integrated approach termed 'systems biology'. The huge advantage in this approach is that the studies can examine people (i.e. populations, sub-populations - based on genes or disease - and individuals), food, life-stage and life-style without preconceived ideas.

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Nutrigenomics

  1. 1. NUTRIGENOMICS More Sachin C.
  2. 2. "If we could give every individual the right amountof nourishment and exercise, not too little and nottoo much, we would have found the safest way tohealth.”"Leave your drugs in the chemists pot if you canheal the patient with food." - Hippocrates
  3. 3. Balanced Diet Pyramid
  4. 4. Family Health at Risk
  5. 5. Nutrients acts as dietary signals Nutritional factors Transcription factors Gene transcription Energy Cellhomeostasis proliferation Nutrient absorption
  6. 6. What are dietary signatures/profiles? Patterns of gene expression, protein expressionand metabolite production in response to particularnutrients or nutritional regimes can be viewed asdietary signaturesHow can these dietary signatures been used inNutrigenomics research? Nutrigenomics seeks to examine these dietarysignatures in specific cells, tissues and organisms,and to understand how nutrition influenceshomeostasis. Dietary signatures can be used toidentify (early) molecular biomarkers
  7. 7. Nutritional Genomics• Nutrigenomics studies modulating effects of nutrients on gene structure and expression; related science of Nutrigenetics researches patients’ unique responses-caused by specific genetic variations-to macro- and micronutrients (Desiere, 2004)• “… the interface between the nutritional environment and cellular/ genetic processes” (Kaput and Rodriguez, 2004)• Next frontier in the post genomic age• Off shoot of HGP
  8. 8. Health effects of the nutrient and non-nutrient components of food relates specific molecular interactions (Ommen et al., 2004)
  9. 9. Two sub definitions • Two sides of a coin • Dynamic cause–effect relationship between nutrition and the human genome (Mutch et al., 2005)
  10. 10. Nutrigenomics Nutrigenetics Aims to study the genome- wide  Concerned with how geneticinfluence of nutrition variation determines an individual’s disease risk, nutrient requirements, metabolic response and Concerned with the functional responsiveness to a bioactiveeffect of nutrient or non-nutrient dietary components orfood components on the genome, nutritional therapytranscriptome, proteome andmetabolome (Muller and Kersten, 2003) (DeBusk et al., 2005)
  11. 11. Two-way interaction between nutrition and the human genome (Roche, 2004)
  12. 12. The direct and indirect effects of nutrients (Muller and Kersten, 2003)
  13. 13. Challenge• Common, polygenic, diet-related diseases which are composite of multiple genetic variants interacting with multiple environmental factors• To develop and apply a robust nutritional genomics research approach that is sensitive enough to take account of both genetic heterogeneity and diverse nutrient exposure
  14. 14. Nutrigenomics – A Systems Biology Approach
  15. 15. Bioactive food components influence genetic and epigenetic events
  16. 16. Dietary factors and the regulation of DNA methylation
  17. 17. “omics” of nutrition to identify how dietary factors contribute to phenotype
  18. 18. Implications of approach• New way of dealing with nutrigenomics data aims to integrate all of the gene expression and/or proteomic data and present this information as a ‘complete’ biological process• Multivariate analytical approach• Key to our understanding of nutrition and health
  19. 19. Health Effect of Dietary Fatty Acids and TFs• Fatty acids had important metabolic effects with respect to energy homeostasis, lipoprotein metabolism, glucose homeostasis and inflammation• Potent cellular molecules that interact with several transcription factors, which in turn explains the diverse health effect of altered dietary fat intake
  20. 20. Lipid sensitive transcription factors
  21. 21. Cross talk between lipid sensitive TFs PPARα activation inhibits LXR binding regulation Expression of SREBP-1c & other downstream lipogenic genes (Clarke et al., 1999)
  22. 22. Metabolomics – The Newest Tool• Utilizes analytical chemistry technologies, 1) NMR 2) MS• Help Capture Data On Complete Metabolome• May provide the comprehensive biomarker of multiple metabolites to asses nutrient status metabolic responses and disease predispositions
  23. 23. Metabolism approach• n-6 PUFA and n-3 PUFA interventions• Hepatic transcriptome and lipid metabolome completed• Diets supplemented with AA or EPA or fish oil• Studied down-regulation of hepatic SCD1 and not SCD2 or SCD3• SCD1 potential therapeutic target to protect against CVD and diet-induced obesity
  24. 24. Nutrigenetics – Individual Genetic Variability And Responsiveness• Human genome 99.9% identical• 0.1% variation principally due to SNPs, responsible for 90% variation among individuals• Functional and Non-functional SNPs• Gene-Nutrient interaction concept important• Standard “one-size-fits-all” strategy is no longer considered to be good practice
  25. 25. Interrelationships Among Specific Nutrients, Genes and Health Outcomes• Green Tea (Camellia sinensis) - Potent antioxidants-prevent certain cancers and heart disease - Some women appear to show a reduction in breast cancer - Have gene variant that produces less active form of gene enzyme COMT inactivating carcinogenic compounds
  26. 26. Contd…• Curcumin: -yellow pigment from turmeric (Curcuma longa) - basic ingredient in Curries -produce suppressing genes for enzymes that produce inflammatory prostaglandins e.g. cyclooxygenase-2 (COX-2)• Prostaglandins linked to colon cancer, heart disease, arthritis, and Alzheimer’s disease• “curry-eating people of India have the world’s lowest incidence of Alzheimer’s disease” - Sally A. Frautschy, Professor of Neurology, University of California
  27. 27. PERSONALIZED NUTRITION • Pioneer worker in Nutrigenomics • Talks about virtual labSenior Scientist Jose Ordovas Tufts Human Nutrition • Personalized nutrition for Research Center on Aging everyone in cost effective manner and behavioral guidelines for each individual depending on ones health status to reduce disease predisposition • To be cautious regarding interpretations we need to move step-by-step like solving puzzle to create big picture
  28. 28. Step 1Collecting (patient) information• Physical examination• Questionnaire  Diet  Disease history  Lifestyle
  29. 29. Step 2Looking for genetic differences that mirror physical differences in patients – PCR – Gel electrophoresis – DNA sequencing
  30. 30. Step 3Examining the foodsYou can separate the different chemicals that make up a food using their different properties by: – Different solubility – Chromatography
  31. 31. Step 4Test the effect of the food components on cells• Cell lines (luminescence)
  32. 32. Step 5Test the food components of the cells in vivo• Animal models (micro-arrays)
  33. 33. What happens next?• Make individualised dietary recommendations to patients?• Produce dietary supplements to enhance individual genetic potential?• Produce dietary supplements to suppress gene activity?
  34. 34. Commercialization• http://www.mycellf.com/MyCellfProgram.aspx• Sciona Inc. (www.sciona.com)• Genelex Inc. (www.genelex.com)
  35. 35. CASE STUDIES
  36. 36. INTRODUCTION• (PPARs), α and Ƴ ligand-activated transcriptional factors regulating lipid and lipoprotein metabolism; glucose homeostasis, and inflammation• PPAR α- Expressed in liver -promotes microsomal ω-oxidation and peroxisomal β- oxidation of Fatty acids Ligands- Fatty acids and FFs• PPAR Ƴ- Expressed in Adipose tissue -Ligands- UFAs• Isohumulones generated from humulones in Hops imparting bitter taste to beer• Dual Agonists of both PPAR TFs (Yajimi et al., 2004)
  37. 37. Research Methodology• Materials: IHE by extracting hops with supercritical co2; isomerised in alkaline condition• Animals and Diets: -C57BL/6NCrj and PPAR α-/- /129S4/SvJae mice -AIN-76A Diet• DNA Microarray analysis: -RNA extraction -cDNA labelling Cy3 or Cy5• QPCR: primers designed with primer3 software• Statistical Analysis: One way ANOVA
  38. 38. Results and DiscussionBiochemical parameters in male mice Effect of IHE and FF :
  39. 39. Plasma Totalcholesterol HDL cholesterolTriglycerides Non esterified FFA
  40. 40. Transcriptional profiling and QPCR analyses in male C57BL/6N mice• 8245 genes analysed out of which approx.1200 shown enough signal intensity• IHE-20 and FF-100 genes: 2 fold or more expression• No significant difference when diet supplemented with Cholesterol
  41. 41. Dose-dependent induction of representative PPARα target genes in liver, by IHE
  42. 42. Gender differences in IHE-induced hepatic gene expression.
  43. 43. Conclusion• Data showed IHE increased the expression of hepatic PPARα target genes• Effect similar to FF• IHE modulated blood lipid status by activating PPARα• So IHE may be potentially therapeutic for preventing T2DM and Atherosclerosis• Beer consumption might actually help to prevent alcoholic liver disease ‼
  44. 44. Introduction• UVA exposure cause skin aging by singlet oxygen (1O2)-dependent pathways• Gene regulation through TF AP-2.• β-carotene (βC) can protect skin since: 1. 1O2 quencher 2. scavenges ROS 3. Mildly reduces sunburns• HaCaT human keratinocytes used.(2 d, 1.5 µM)
  45. 45. Research Methodology• βC and UVA Treatment of keratinocytes• Affymetrix GeneChip Analysis: Five independent, factorially designed cell irradiation experiments analyzed by microarray hybridization.• QRT-PCR to confirm key gene regulations in three independent cell irradiation experiments at different βC concentrations.(0.5, 1.5 and 3 µM)• Apoptosis Assay : Caspase 3-activity 5 h after irradiation using CaspACE Assay System
  46. 46. Results and Discussion• Cellular uptake of βC confirmed by HPLC• 1458 genes significantly regulated by at least one treatment: a) βC regulated 381 genes b) UVA influenced 568 genes c) UVA / βC regulated 1142 genes d) not regulated by single treatment 610 genes
  47. 47. βC effects in unirradiated keratinocytes Differential regulationGenes upregulatedGenes downregulated Receptor innate immunity Key process- skin aging Marker genes Shown RA-independent effects
  48. 48. Down regulation βC concentration dependently induced caspase-3 activity in ultraviolet light A (UVA)-irradiated keratinocytes. βC promoted keratinocyte differentiation but not terminal steps
  49. 49. Ultraviolet light A (UVA) effects in keratinocytes
  50. 50. βC effects in UVA-irradiated keratinocytes Differentially regulated Quenched by proinflammatory genes βC Enhanced tanning supplemented UVAβC supplementation may indeed reduce wrinkling. (Battistutta et al., 2000)
  51. 51. Contd…• RA target genes down regulated by UVA• Further promoted differentiation in irradiated keratinocytes• This may render combined UVA / βC treatment a promising therapy for skin disorders associated with disturbed differentiation. e.g. Psoriasis.
  52. 52. Proposed relationship of the modes of actionof β -carotene to its influence on ultraviolet light A-induced biological processes.
  53. 53. Conclusion
  54. 54. Discussion

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