Nutrigenomics: An Emerging Scientific Discipline 
(Nutrient on gene Expression) 
SPEAKER 
Sukanta Das 
Nutrition and Deities 
Vidyasagar University, Midnapore- 721 102
Terminology 
1. Genetics 
2. Genomics 
3. Nutrigenetics 
4.Nutrigenomics 
2003-Debusk 
Mechanism for inheriting specific traits 
Which genes and proteins are activated 
under different conditions 
Effects of genetic variation on Nutrient 
influences on health and diseases of an 
individual. Ex- Phenylketonuria, Lactose 
Intolerance 
Effect of bio active dietary components on 
the expression of genes & ultimately health. 
EX- DHA on lipolysis
Nutrigenomics Integrative System Biology 
Nutrition Science 
Uses the tools & 
concept from 
Botany Molecular 
Biology 
Genetics 
Biochemistry 
Genomics 
Nutrient 
Gene Disease
Pathway of nutritional genomics/ 
Nutrigenomics 
Other Lifestyle 
factors/ Smoking/ 
Alcoholism 
Cholesterol 
and Fat 
1a. Disease causing nutrients 
1b. Health promoting nutrients 
Health friendly 
nutrients 
CVD 
Health up gradation
Evolution in the concept of Nutrient 
 Nutrient as fuel (Energy yielding concept) 
Nutrient as cofactor (Metabolic regulator concept) 
Nutrient as pharmaceutical agent (Nutraceuticals) (Health protective & Disease 
preventive concept) 
 Nutrient as gene modulator (Nutrigenomics) 
Gene modulating concept 
Nutriepigenetic 
(Nutrient alter the methylation of DNA at specific 
developmental period i.e. succkling period)
Evidences of Nutrigenomics 
1. Nutrient at specific critical period of development 
Modulate gene imprintation 
Feeding of Royal jelly to first 3 days of immature bees Convert it into queen 
Muller-2003 
2. Epidemiological evidence 
Diet rich in fruits, vegetable, whole grain 
Decrease the risk of chronic degenerative disease 
Waterland- 2003 
3. Methyl enrich diet to the mother (rat) during gestational period 
Produce life long change in the color of the pups. (Nutriepigenetics) 
4. Evolutionary aspect of diet ( Simopoulos-2002) (Asian Pacific J. Clin. Nut.) 
5. Unfold the different domains of Nutrigenomics (5th International 
Phytochemical conference 18-19th Oct, 2004. Calofornia)
0 
40 
30 
20 
10 
Hunter Agricultural Industrial 
Gatherer 
-4x106 -10000 
Trans fat 
1800 1900 2000 
600 
100 
Mg/day 
30 
10 
% of calories from fat 
0 
Total fat
Ethnic differences in fatty acid concentration 
and Mortality from CVD 
Europe and USA Japan Green land/ 
eskimos 
Ratio ω6/ ω3 50 12 1 
Mortality from 
CVD 
45 12 7 
Current value ω6 / ω3 
Japan: 4. 00 
Current India (Rural): 5-6.1 
Current India (Urban): 38-50 
USA: 16.74
Four Possible Mechanism 
Mechanism of Gene- Nutrient Interaction 
Example 
Example 
R 
cAMP 
kinase 
Protein 
CRE 
phosphorilation 
mRNA
Atherosclerosis and ω3PUFA 
What is ω3PUFA CH3-CH2-CH2-CH2-COOH 
ω3 
ω3 
What is Atherosclerosis 
LDL-C 
OX-LDL-C-LDL- 
C 
Receptor bound OX-LDL in endothelial cell 
Foam cells 
PAF 
EDGF 
Platelets streak 
Endothelial level streak 
Atherosclerosis 
Clot 
Plaque
Arachidonic 
acid 
Ecosapentaenoic 
acid 
Diet Diet 
Upregulate EDRF 
(Endothelium Derived 
Relaxing Factor ) 
Downregulate PDGF (Platelet 
Derived Growth Factor) in 
Endothelial cell 
Mitogenic activity and 
chemoattracting activity of 
PDGF are erased 
Transgenic endothelial cells with ω3 fatty acid desaturase from round worm C. elegans 
Endothelial cells fed ω3 fatty acid 
Cellular level ω3 fatty acid 
Downregulate PDGF and Upregulate EDRF
RNA Polymerase 
entry side 
SRE AUG UAA 
NH 
PPAR / RXR – Where SRE consist of an AGGTCA direct repeat with 
differ in nucleotide number in the spacers 
RXR AGGTCA N2 AGGTCA 
PPAR AGGTCA N5 AGGTCA 
DNA 
{ 
Promoter 
PPAR + ω3 fatty acid RXR +Retinoids 
Heterodimer 
ω3 Retinoids 
PPAR RXR 
GENE EPA DHA 
FAS 
Acyl -coA 
oxidase 
Switch on/ Switch off/ the 
Form in cytosol Nucleus Bind to SRE concern gene expression
Model for upregulation of gene expression by steroid receptor 
ligand complex 
D Pol- II 
A 
B J F E 
Unstabilize preinitiation 
complex for transcription 
H 
SRE TATA 
when SRE is blank 
mRNA 
A 
B 
RC 
D Pol- II 
A 
B J F E 
H 
SRE TATA 
mRNA 
RC 
RC-stabilize preinitiation 
complex for transcription 
when SRE is captured by RC
Hypothesis for downregulation of gene expression by steroid 
receptor ligand complex 
mRNA 
Gene Z 
USP 
SRE SRE 
TF-□D 
TATA 
A protein complex binds with upstream promoter (USP) and activates transcription 
via interaction with TATA protein i.e. TF-□D 
SR SR 
mRNA 
Gene Z 
USP 
SRE SRE 
TF-□D 
TATA 
SR SR 
SR binds with SRE, displace USP complex and remove the USP mediated stabilization 
of TF-□D protein- shutting down transcription
RAM SHYAM 
Both are suffering from mild heart 
attack 
HDL-C Low dietary fat HDL-C 
Results conflict/ Dilemma doctors/ Dietitians 
Explanation 
Hepatic Lipase (HL) 
Overexpression 
HDL-C 
Polymorphism of HL-gene at 514 bp upstream 
transcription initiation site (SNP) 
C T substitution 
C/C alleles C/C or C/T alleles 
Low dietary fat (HDL-C) Low fat diet (HDL-C) 
< 30% of energy
MECHANISM 
A G T C G A 
OH radical/ 
Low antioxidative diet 
A G T Hc G A 
DNA single strand 
Replication 
DNA double strand 
{ 
T C A A C T 
A G T T G A C T substitution at USP gene
ARE Oxido- Reductase gene 
Oxido- Reductase 
NFE2R2 
Lycopene 
Ligand Complex 
NFE2R2 (Transcription factor) 
(Nuclear factor E2 related 
factor- 2) 
Control phase- II of Bio-transformation 
Pro-carcinogen 
Lycopene 
mRNA 
Lycopene
Challenges with Product 
Development 
Studies must be ‘product specific’ not ‘ingredient 
specific’ 
Standard foe effective and safe nutritional product 
Genetic testing of the product 
Dietary intervention based upon Nutritional 
requirement, Nutritional status and Genotype
Our 
Slogan 
1. “NUTRITION BE YOUR MEDICINE AND MEDICINE 
BE YOUR FOOD” 
2. “HEALTH COMES FROM THE FARM, NOT FROM THE 
PHARMACY”
nutrigenomics

nutrigenomics

  • 1.
    Nutrigenomics: An EmergingScientific Discipline (Nutrient on gene Expression) SPEAKER Sukanta Das Nutrition and Deities Vidyasagar University, Midnapore- 721 102
  • 2.
    Terminology 1. Genetics 2. Genomics 3. Nutrigenetics 4.Nutrigenomics 2003-Debusk Mechanism for inheriting specific traits Which genes and proteins are activated under different conditions Effects of genetic variation on Nutrient influences on health and diseases of an individual. Ex- Phenylketonuria, Lactose Intolerance Effect of bio active dietary components on the expression of genes & ultimately health. EX- DHA on lipolysis
  • 3.
    Nutrigenomics Integrative SystemBiology Nutrition Science Uses the tools & concept from Botany Molecular Biology Genetics Biochemistry Genomics Nutrient Gene Disease
  • 4.
    Pathway of nutritionalgenomics/ Nutrigenomics Other Lifestyle factors/ Smoking/ Alcoholism Cholesterol and Fat 1a. Disease causing nutrients 1b. Health promoting nutrients Health friendly nutrients CVD Health up gradation
  • 5.
    Evolution in theconcept of Nutrient  Nutrient as fuel (Energy yielding concept) Nutrient as cofactor (Metabolic regulator concept) Nutrient as pharmaceutical agent (Nutraceuticals) (Health protective & Disease preventive concept)  Nutrient as gene modulator (Nutrigenomics) Gene modulating concept Nutriepigenetic (Nutrient alter the methylation of DNA at specific developmental period i.e. succkling period)
  • 6.
    Evidences of Nutrigenomics 1. Nutrient at specific critical period of development Modulate gene imprintation Feeding of Royal jelly to first 3 days of immature bees Convert it into queen Muller-2003 2. Epidemiological evidence Diet rich in fruits, vegetable, whole grain Decrease the risk of chronic degenerative disease Waterland- 2003 3. Methyl enrich diet to the mother (rat) during gestational period Produce life long change in the color of the pups. (Nutriepigenetics) 4. Evolutionary aspect of diet ( Simopoulos-2002) (Asian Pacific J. Clin. Nut.) 5. Unfold the different domains of Nutrigenomics (5th International Phytochemical conference 18-19th Oct, 2004. Calofornia)
  • 7.
    0 40 30 20 10 Hunter Agricultural Industrial Gatherer -4x106 -10000 Trans fat 1800 1900 2000 600 100 Mg/day 30 10 % of calories from fat 0 Total fat
  • 8.
    Ethnic differences infatty acid concentration and Mortality from CVD Europe and USA Japan Green land/ eskimos Ratio ω6/ ω3 50 12 1 Mortality from CVD 45 12 7 Current value ω6 / ω3 Japan: 4. 00 Current India (Rural): 5-6.1 Current India (Urban): 38-50 USA: 16.74
  • 9.
    Four Possible Mechanism Mechanism of Gene- Nutrient Interaction Example Example R cAMP kinase Protein CRE phosphorilation mRNA
  • 10.
    Atherosclerosis and ω3PUFA What is ω3PUFA CH3-CH2-CH2-CH2-COOH ω3 ω3 What is Atherosclerosis LDL-C OX-LDL-C-LDL- C Receptor bound OX-LDL in endothelial cell Foam cells PAF EDGF Platelets streak Endothelial level streak Atherosclerosis Clot Plaque
  • 11.
    Arachidonic acid Ecosapentaenoic acid Diet Diet Upregulate EDRF (Endothelium Derived Relaxing Factor ) Downregulate PDGF (Platelet Derived Growth Factor) in Endothelial cell Mitogenic activity and chemoattracting activity of PDGF are erased Transgenic endothelial cells with ω3 fatty acid desaturase from round worm C. elegans Endothelial cells fed ω3 fatty acid Cellular level ω3 fatty acid Downregulate PDGF and Upregulate EDRF
  • 12.
    RNA Polymerase entryside SRE AUG UAA NH PPAR / RXR – Where SRE consist of an AGGTCA direct repeat with differ in nucleotide number in the spacers RXR AGGTCA N2 AGGTCA PPAR AGGTCA N5 AGGTCA DNA { Promoter PPAR + ω3 fatty acid RXR +Retinoids Heterodimer ω3 Retinoids PPAR RXR GENE EPA DHA FAS Acyl -coA oxidase Switch on/ Switch off/ the Form in cytosol Nucleus Bind to SRE concern gene expression
  • 13.
    Model for upregulationof gene expression by steroid receptor ligand complex D Pol- II A B J F E Unstabilize preinitiation complex for transcription H SRE TATA when SRE is blank mRNA A B RC D Pol- II A B J F E H SRE TATA mRNA RC RC-stabilize preinitiation complex for transcription when SRE is captured by RC
  • 14.
    Hypothesis for downregulationof gene expression by steroid receptor ligand complex mRNA Gene Z USP SRE SRE TF-□D TATA A protein complex binds with upstream promoter (USP) and activates transcription via interaction with TATA protein i.e. TF-□D SR SR mRNA Gene Z USP SRE SRE TF-□D TATA SR SR SR binds with SRE, displace USP complex and remove the USP mediated stabilization of TF-□D protein- shutting down transcription
  • 15.
    RAM SHYAM Bothare suffering from mild heart attack HDL-C Low dietary fat HDL-C Results conflict/ Dilemma doctors/ Dietitians Explanation Hepatic Lipase (HL) Overexpression HDL-C Polymorphism of HL-gene at 514 bp upstream transcription initiation site (SNP) C T substitution C/C alleles C/C or C/T alleles Low dietary fat (HDL-C) Low fat diet (HDL-C) < 30% of energy
  • 16.
    MECHANISM A GT C G A OH radical/ Low antioxidative diet A G T Hc G A DNA single strand Replication DNA double strand { T C A A C T A G T T G A C T substitution at USP gene
  • 17.
    ARE Oxido- Reductasegene Oxido- Reductase NFE2R2 Lycopene Ligand Complex NFE2R2 (Transcription factor) (Nuclear factor E2 related factor- 2) Control phase- II of Bio-transformation Pro-carcinogen Lycopene mRNA Lycopene
  • 18.
    Challenges with Product Development Studies must be ‘product specific’ not ‘ingredient specific’ Standard foe effective and safe nutritional product Genetic testing of the product Dietary intervention based upon Nutritional requirement, Nutritional status and Genotype
  • 19.
    Our Slogan 1.“NUTRITION BE YOUR MEDICINE AND MEDICINE BE YOUR FOOD” 2. “HEALTH COMES FROM THE FARM, NOT FROM THE PHARMACY”