Transcript Introduction Genomics, proteomics, metabolomics

INTRODUCTION
Nutrigenomics
Dr. Muhamad Firdaus
Nutrigenomics
The study of how naturally occurring
chemicals in foods alter molecular expression
of genetic information in each individual.
When a gene is activated or expressed, a
protein is produced
Gene expression patterns produce a phenotype, which
represents the physical characteristics or observable
traits of an organism, e.g., hair color, weight, or
presence or absence of disease
Genes alone do not necessary produce phenotypic
traits
Phenotypic expression is influenced by nutrition
Nutrition-Gene Interaction
1. Direct interactions
Nutrients, sometimes after interacting with a receptor, behave as
transcription factors that can bind to DNA and acutely induce gene
expression
2. Epigenetic interactions
Nutrients can alter the structure of DNA so that gene expression is
chronically altered
3. Genetic variation
Common genetic variations such as single-nucleotide polymorphisms
(SNPs) can alter the expression or functionality of genes
BIOLOGICAL NETWORKS
Intracellular regulations
Cell-cell comuniacations
Organ networks/homeostasis
MAIN HEALTH-RELATED CHALLENGES
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Cardiovascular
Cancer
Diabetes-obesity
Undernutrition/malnutrition
Infectious diseases
Allergies
Ageing process
BIOACTIVE FOOD COMPONENTS CAN MODIFY
TRANSCRIPTION, TRANSLATION AND METABOLISM
EFFECTS OF SELENIUM ON CERTAIN GENES
Cancer Res, 2002
BIOACTIVE FOOD COMPONENTS:
GENETIC, EPIGENETIC AND PROTEOMIC EFFECTS
Milner J Nutr 2004
PARTIAL LIST OF BIOACTIVE FOOD COMPONENTS:
WITH POSSIBLE EFFECTS ON CANCER
INTER-RELATIONSHIP BETWEEN BIOACTIVE FOOD COMPONENTS
AND EVENTS INVOLVED IN THE CANCER PROCESS
FATE AND ACTIVITIES OF NUTRIENTS IN
THE CELL
may act directly
as ligands for
transcription
factor
receptors
(pathway A)
Kaput J, Physiol Genomics 2004
FATE AND ACTIVITIES OF NUTRIENTS IN
THE CELL
may be metabolized
by metabolic
pathways

altering
concentrations of
substrates /
intermediates
(pathway B)
Kaput J, Physiol Genomics 2004
FATE AND ACTIVITIES OF NUTRIENTS IN
THE CELL
May be involved
in gene
regulation
or cell-signaling
(pathway C)
Kaput J, Physiol Genomics 2004
NUCLEAR RECEPTORS, DIETARY LIGANDS
Kaput J, Physiol Genomics 2004
MICRONUTRIENT DEFICIENCY DNA DAMAGE WITH HEALTH EFFECTS
From: Kaput J: Physiol Genomics 2004 Ref 2: Ames, Toxicol Lett 1998
NUTRIGENOMICS AND NUTRIGENETICS:
TWO SIDES OF A COIN
• For personalized
nutrition:
– effects of diet on
body-metabolism
– influence of
genotype on
nutritionally related
diseases
• must be
Mutch, FASEB 2005
considered
Elliot, BMJ 2002
NUTRITIONAL CONSEQUENCES OF CELLULAR
PROCESS WITH GENETIC POLYMORPHISMS
NUTRITIONAL GENOMICS AND BIOMARKER DISCOVERY
THE STEPS INVOLVED IN GENE EXPRESSION
NUTRITIONAL GENOMICS AND BIOMARKER DISCOVERY
DIET (NUTRIENTS) CAN MODULATE THESE PROCESSES
FROM CELL TO POPULATION
NUTRITIONAL GENOMICS AND BIOMARKER DISCOVERY
FUNCTIONAL GENOMICS TECHNIQUES CAN ANALYZE
EACH STAGE, WITH APPROPRIATE BIOMARKERS
Assesment of nutrient
requirements by
„omics“- based
analyses
Joung: J.Nutr 2001, Oliver: Nature 2000,
Go: J. Nutr 2003
Stover: Physiol Genomics 2004
LC-PUFA:
LONG CHAIN POLYUNSATURATED FATTY ACIDS
A typical example of complex, bioactive
molecules in nutrigenomics
Epidemiological studies on LC-PUFA:
Consumption of LC-PUFA beneficially affect physiological
processes such as :
- growth, neurological development,
- lean and fat mass accretion,
- reproduction,
- Innate and acquired immunity,
- infectious pathologies of viruses,
- bacteria and parasites;
LC-PUFA:
Long chain
polyunsaturated fatty
acids
Mutch, FASEB J
2005
- the incidence and severity of virtually all
chronic
- and degenerative diseases
cancer, atherosclerosis, stroke, arthritis, diabetes,
osteoporosis, and neurodegenerative, inflammatory
and skin diseases
MODERN NUTRIGENOMIC TECHNOLOGIES + BIOINFORMATICS CAN
TO REVEAL THE COMPLEXITY OF LC-PUFA SIGNALING
According to microarray studies:
LC-PUFA can mediate the functions
of
several transcription factors,
cell-cycle regulatory genes,
RNA transcription processes,
prostaglandin synthesis,
inducible nitric oxide synthase
and related proinflammatory
genes
BIOLOGICAL NETWORK TRIGGERED AFTER THE CONSUMPTION
OF LC-PUFA
• LC-PUFA actions are
mediated by
transcription factors,
such as PPAR and
SREBP.
• Highlighted in blue
are known functional
and /or physical
interactions between
PPAR- and other
genes
Mutch, FASEB 2005
MODERN NUTRIGENOMIC TECHNOLOGIES + BIOINFORMATICS CAN
TO REVEAL THE COMPLEXITY OF LC-PUFA SIGNALING:
Further work:
small inhibiting RNA
technology,
alternate analytical
platforms (proteins,
metabolites) etc.
can clarify the
biological functions,
mediated by dietary
lipids.
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