INTRODUCTION Nutrigenomics Dr. Muhamad Firdaus

Nutrigenomics. The study of how naturally occurring 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 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 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 considered Mutch, FASEB 2005

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; - 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

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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