Nutrigenomics: An Emerging Scientific Discipline

(Nutrient on gene Expression)

Sukanta Das

Nutrition and Deities

Vidyasagar University, Midnapore- 721 102

SPEAKER

1. Genetics

2. Genomics

3. Nutrigenetics

4.Nutrigenomics2003-Debusk

Terminology

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

GeneticsGenomics

Biochemistry

Nutrient

Gene Disease

Pathway of nutritional genomics/

Nutrigenomics

Other Lifestyle

factors/ Smoking/

Alcoholism

Cholesterol

and Fat

1a. Disease causing nutrients

Health friendly

nutrients

1b. Health promoting nutrients

CVDHealth up gradation

Evolu

tion

in

th

e co

nce

pt

of

Nu

trie

nt

(Nutrient alter the methylation of DNA at specific

developmental period i.e. succkling period)

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)

Nutriepigenetic

Gene modulating concept

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

2. Epidemiological evidence

Muller-2003

Diet rich in fruits, vegetable, whole grain

Decrease the risk of chronic degenerative disease

3. Methyl enrich diet to the mother (rat) during gestational period

Waterland- 2003

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

10

20

40

30

-4x106 -10000 1800 1900 2000

Hunter Agricultural Industrial

Gatherer

Trans fat

Mg/day

10

30

600

100

% o

f ca

lori

es f

rom

fa

t

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

Mec

han

ism

of

Gen

e-

Nu

trie

nt

Inte

ract

ion

Four Possible Mechanism

Exam

ple

Example

R

cAMP

kinase

Protein phosphorilation

CRE

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

Plaque

Clot

Atherosclerosis

Diet Diet

Arachidonic

acid

Ecosapentaenoic

acid

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

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

RNA Polymerase

entry side

DNA

{ SRE AUG UAA

Promoter

NH

+RetinoidsPPAR + ω3 fatty acid RXR

PPAR RXR

Heterodimer

ω3 Retinoids

Switch on/ Switch off/ the concern gene expression Form in cytosol Nucleus Bind to SRE

GENE EPA DHA

FAS

Acyl -coAoxidase

Model for upregulation of gene expression by steroid receptor

ligand complex

Pol- IIDA

B J F E

H

SRE TATA

mRNA

Unstabilize preinitiation

complex for transcription

when SRE is blank

A

BRC

Pol- IIDA

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

SRE SRE

USP

TATA

TF-□D

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

SRE SRE

USP

TATA

TF-□D

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

Low dietary fat HDL-CHDL-C

Results conflict/ Dilemma doctors/ Dietitians

Exp

lan

atio

n

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 AG

A G T Hc AG

OH radical/

Low antioxidative diet

DNA single strand

Replication

DNA double strand T C A A TC

A G T T AG{C T substitution at USP gene

Oxido- Reductase

Ligand Complex

NFE2R2 (Transcription factor)(Nuclear factor E2 related factor- 2)

ARE Oxido- Reductase gene

NFE2R2

Lycopene

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

1. “NUTRITION BE YOUR MEDICINE AND MEDICINEBE YOUR FOOD”

2. “HEALTH COMES FROM THE FARM, NOT FROM THEPHARMACY”

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