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, aprotein 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 interactionsNutrients, sometimes after interacting with a receptor, behave as transcription factors that can bind to DNA and acutely induce geneexpression

2. Epigenetic interactionsNutrients can alter the structure of DNA so that gene expression ischronically altered

3. Genetic variationCommon 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

• Cardiovascular• Cancer• Diabetes-obesity• Undernutrition/malnutrition• Infectious diseases• Allergies• Ageing process

BIOACTIVE FOOD COMPONENTS CAN MODIFY TRANSCRIPTION, TRANSLATION AND METABOLISM

Cancer Res, 2002

EFFECTS OF SELENIUM ON CERTAIN GENES

Milner J Nutr 2004

BIOACTIVE FOOD COMPONENTS:GENETIC, EPIGENETIC AND PROTEOMIC EFFECTS

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

Kaput J, Physiol Genomics 2004

NUCLEAR RECEPTORS, DIETARY LIGANDS

From: Kaput J: Physiol Genomics 2004 Ref 2: Ames, Toxicol Lett 1998

MICRONUTRIENT DEFICIENCY - DNA DAMAGE WITH HEALTH EFFECTS

Mutch, FASEB 2005

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 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 ANALYZEEACH STAGE, WITH APPROPRIATE BIOMARKERS

Joung: J.Nutr 2001, Oliver: Nature 2000,

Go: J. Nutr 2003

Assesment of nutrient requirements by „omics“- basedanalyses

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;

- the incidence and severity of virtually all

chronic

- and degenerative diseases

cancer, atherosclerosis, stroke, arthritis, diabetes,

osteoporosis, and neurodegenerative, inflammatory

and skin diseases

LC-PUFA: Long chain polyunsaturated fatty acids

Mutch, FASEB J 2005

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

MODERN NUTRIGENOMIC TECHNOLOGIES + BIOINFORMATICS CAN

TO REVEAL THE COMPLEXITY OF LC-PUFA SIGNALING

BIOLOGICAL NETWORK TRIGGERED AFTER THE CONSUMPTION

OF LC-PUFA

• LC-PUFA actions are mediated bytranscription factors, such as PPAR and SREBP.

• Highlighted in blueare known functional and /or physical interactions betweenPPAR- and other genes

Mutch, FASEB 2005

Further work:

small inhibiting RNA technology,

alternate analytical platforms (proteins, metabolites) etc.

can clarify the biological functions,

mediated by dietary lipids.

MODERN NUTRIGENOMIC TECHNOLOGIES + BIOINFORMATICS CAN

TO REVEAL THE COMPLEXITY OF LC-PUFA SIGNALING:

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